tag:theconversation.com,2011:/global/topics/human-genome-5870/articlesHuman genome – The Conversation2023-08-24T04:51:52Ztag:theconversation.com,2011:article/2121122023-08-24T04:51:52Z2023-08-24T04:51:52ZThe ‘weird’ male Y chromosome has finally been fully sequenced. Can we now understand how it works, and how it evolved?<p>The Y chromosome is a never-ending source of fascination (particularly to men) because it bears genes that determine maleness and make sperm. It’s also small and seriously weird; it carries few genes and is full of junk DNA that makes it horrendous to sequence. </p>
<p>However, new “<a href="https://www.nature.com/articles/s41592-022-01730-w">long-read</a>” sequencing techniques have finally provided a reliable sequence from one end of the Y to the other. The paper describing this Herculean effort has been <a href="https://www.nature.com/articles/s41586-023-06457-y">published</a> in Nature.</p>
<p>The findings provide a solid base to explore how genes for sex and sperm work, how the Y chromosome evolved, and whether – as predicted – it will disappear in a few million years.</p>
<h2>Making baby boys</h2>
<p>We have known for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443938/#">about 60 years</a> that specialised chromosomes <a href="https://theconversation.com/what-makes-you-a-man-or-a-woman-geneticist-jenny-graves-explains-102983">determine birth sex</a> in humans and other mammals. Females have a pair of X chromosomes, whereas males have a single X and a much smaller Y chromosome.</p>
<p>The Y chromosome is male-determining because it bears a gene <a href="https://pubmed.ncbi.nlm.nih.gov/1695712/">called SRY</a>, which directs the development of a ridge of cells into a testis in the embryo. The embryonic testes make male hormones, and these hormones direct the development of male features in a baby boy.</p>
<p>Without a Y chromosome and a SRY gene, the same ridge of cells develops into an ovary in XX embryos. Female hormones then direct the development of female features in the baby girl.</p>
<h2>A DNA junkyard</h2>
<p>The Y chromosome is very different from X and the 22 other chromosomes of the human genome. It is smaller and bears few genes (only 27 compared to about 1,000 on the X).</p>
<p>These include SRY, a few genes required to make sperm, and several genes that seem to be critical for life – many of which have partners on the X.
Many Y genes (including the sperm genes RBMY and DAZ) are present in multiple copies. Some occur in weird loops in which the sequence is inverted and genetic accidents that duplicate or delete genes are common.</p>
<p>The Y also has a lot of DNA sequences that don’t seem to contribute to traits. This “junk DNA” is comprised of highly repetitive sequences that derive from bits and pieces of old viruses, dead genes and very simple runs of a few bases repeated over and over. </p>
<p>This last DNA class occupies big chunks of the Y that literally glow in the dark; you can see it down the microscope because it preferentially binds fluorescent dyes.</p>
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Read more:
<a href="https://theconversation.com/we-discovered-a-missing-gene-fragment-thats-shedding-new-light-on-how-males-develop-147348">We discovered a missing gene fragment that's shedding new light on how males develop</a>
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<h2>Why the Y is weird</h2>
<p>Why is the Y like this? Blame evolution.</p>
<p>We have a lot of evidence that 150 million years ago the X and Y were just a pair of ordinary chromosomes (they still are in birds and platypuses). There were two copies – one from each parent – as there are for all chromosomes.</p>
<p>Then SRY evolved (from an ancient gene with another function) on one of these two chromosomes, defining a new proto-Y. This proto-Y was forever confined to a testis, by definition, and subject to a barrage of mutations as a result of a lot of cell division and little repair. </p>
<p>The proto-Y degenerated fast, losing about 10 active genes per million years, reducing the number from its original 1,000 to just 27. A small “pseudoautosomal” region at one end retains its original form and is identical to its erstwhile partner, the X.</p>
<p>There has been great debate about whether this <a href="http://theconversation.com/sex-genes-the-y-chromosome-and-the-future-of-men-32893">degradation continues</a>, because at this rate the whole human Y would disappear in a few million years (as it already has in some rodents).</p>
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Read more:
<a href="https://theconversation.com/men-are-slowly-losing-their-y-chromosome-but-a-new-sex-gene-discovery-in-spiny-rats-brings-hope-for-humanity-195903">Men are slowly losing their Y chromosome, but a new sex gene discovery in spiny rats brings hope for humanity</a>
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<h2>Sequencing Y was a nightmare</h2>
<p>The first draft of the human genome was completed in 1999. Since then, scientists have managed to sequence all the ordinary chromosomes, including the X, with just a few gaps. </p>
<p>They’ve done this using short-read sequencing, which involves chopping the DNA into little bits of a hundred or so bases and reassembling them like a jigsaw.</p>
<p>But it’s only recently that new technology has allowed sequencing of bases along individual long DNA molecules, producing long-reads of thousands of bases. These longer reads are easier to distinguish and can therefore be assembled more easily, handling the confusing repetitions and loops of the Y chromosome.</p>
<p>The Y is the last human chromosome to have been sequenced end-to-end, or T2T (telomere-to-telomere). Even with long-read technology, assembling the DNA bits was often ambiguous, and researchers had to make several attempts at difficult regions – particularly the highly repetitive region.</p>
<h2>So what’s new on the Y?</h2>
<p>Spoiler alert – the Y turns out to be just as weird as we expected from decades of gene mapping and the previous sequencing.</p>
<p>A few new genes have been discovered, but these are extra copies of genes that were already known to exist in multiple copies. The border of the pseudoautosomal region (which is shared with the X) has been pushed a bit further toward the tip of the Y chromosome.</p>
<p>We now know the structure of the centromere (a region of the chromosome that pulls copies apart when the cell divides), and have a complete readout of the complex mixture of repetitive sequences in the fluorescent end of the Y.</p>
<p>But perhaps the most important outcome is how useful the findings will be for scientists all over the world.</p>
<p>Some groups will now examine the details of Y genes. They will look for sequences that might control how SRY and the sperm genes are expressed, and to see whether genes that have X partners have retained the same functions or evolved new ones.</p>
<p>Others will closely examine the repeated sequences to determine where and how they originated, and why they were amplified. Many groups will also analyse the Y chromosomes of men from different <a href="https://www.biorxiv.org/content/10.1101/2022.12.01.518658v2.abstract">corners of the world</a> to detect signs of degeneration, or recent evolution of function.</p>
<p>It’s a new era for the poor old Y.</p><img src="https://counter.theconversation.com/content/212112/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jenny Graves receives funding from the Australian Research Council.</span></em></p>DNA of the male-determining Y chromosome has been completely sequenced end-to-end, and it’s just as weird as we expected. Will we finally be able to understand how it works?Jenny Graves, Distinguished Professor of Genetics and Vice Chancellor's Fellow, La Trobe UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1847232023-08-22T21:54:17Z2023-08-22T21:54:17ZNew research into genetic mutations may pave the way for more effective gene therapies<figure><img src="https://images.theconversation.com/files/543314/original/file-20230817-8328-bdaz8a.jpg?ixlib=rb-1.1.0&rect=44%2C0%2C5000%2C3315&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A lab dish containing embryos that have been injected with Cas9 protein and PCSK9 sgRNA is seen in a laboratory in Shenzhen in southern China's Guangdong province.</span> <span class="attribution"><span class="source">(AP Photo/Mark Schiefelbein)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/new-research-into-genetic-mutations-may-pave-the-way-for-more-effective-gene-therapies" width="100%" height="400"></iframe>
<p>Consider a living cell, which can have thousands of genes. Now think of these genes as dials that can be tweaked to change how the cell grows in a given environment. Tweaking a gene can either increase or decrease growth, and this is made more complex considering these dials are interconnected with each other, like cogs in a machine. </p>
<p>While scientists are now able to edit genes in laboratory conditions and attempt to produce findings that may lead to cures, evolution has been doing this for billions of years. Evolution is the natural process that turns these dials, allowing populations to adapt. However, unlike scientists, evolution turns these dials randomly as mutations affect the function of genes.</p>
<p>One underlying hypothesis in evolutionary theory — the evolutionary contingency hypothesis — has been that this tuning can have chaotic behaviours. Or, in other words, dials tweaked early in the process can dramatically alter later evolutionary potential.</p>
<p>Stephen Jay Gould was a famous proponent of this theory, arguing in his 1989 book <a href="https://wwnorton.com/books/9780393307009"><em>Wonderful Life</em></a> that since beneficial mutations occur randomly, chance must play an important role in evolutionary diversification.</p>
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Read more:
<a href="https://theconversation.com/does-our-dna-really-determine-our-intelligence-and-health-199266">Does our DNA really determine our intelligence and health?</a>
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<p>If this hypothesis is true, it affects how scientists should edit genes in the laboratory as they will face the chaotic interconnections of our cells. Our work set out to test this hypothesis.</p>
<h2>Resolving an evolutionary paradox</h2>
<p>We can observe the process of evolution in the laboratory under extremely well-controlled conditions. We have done so by growing populations of micro-organisms for hundreds — <a href="https://doi.org/10.7554/eLife.63910">even thousands — of days</a>. </p>
<p>Since these organisms divide and reproduce so quickly, this process represents thousands of generations of growth. These experiments have allowed us to pinpoint <a href="https://doi.org/10.1038/s41586-019-1749-3">precisely when</a>, and how, beneficial mutations co-occur and compete to take over the population.</p>
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<img alt="Image of a human genome." src="https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=418&fit=crop&dpr=1 600w, https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=418&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=418&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=525&fit=crop&dpr=1 754w, https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=525&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/543310/original/file-20230817-41912-psfxhj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=525&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Image readout of a human genome.</span>
<span class="attribution"><span class="source">(NHGRI via AP)</span></span>
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<p>One striking observation from every single one of these experiments is that increases in fitness slow down over time at a rate that is surprisingly reproducible. Despite accumulating different mutations, different populations show remarkably predictable diminishing returns in how fast they adapt.</p>
<p>In contrast with the seemingly chaotic behaviour of mutations, fitness or growth changes are highly predictable. This has led many to hypothesize that this order of mutation is an <a href="https://doi.org/10.3389/fgene.2015.00099">inherent consequence</a> of the way biological systems have evolved. </p>
<p>This striking hypothesis is at odds with the idea that the <a href="https://doi.org/10.1038/s41559-020-01286-y">specifics of an organism’s biology matter for evolution</a>. In other words, it has been difficult to prove that the order in which evolution turns dials has any impact on the future.</p>
<h2>The answer to the paradox</h2>
<p>My team was able to show that the answer to resolving this paradox lies within the interconnected gene network of the cell itself. </p>
<p>For evolution to work, the dial-tuning must be precise: even if the net outcome is beneficial, adjusting one set of linked dials can trickle down and affect other previously correctly placed dials. As evolution continues, the probability of breaking harmoniously-tuned dials grows. This seemingly simple principle explains why the rate of evolutionary improvements typically slows down over time. </p>
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<img alt="A tray containing human DNA samples ready for genetic sequencing." src="https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=521&fit=crop&dpr=1 600w, https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=521&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=521&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=654&fit=crop&dpr=1 754w, https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=654&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/543312/original/file-20230817-23-a743da.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=654&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">A tray containing human DNA samples ready for genetic sequencing.</span>
<span class="attribution"><span class="source">(AP Photo/Patricia McDonnell)</span></span>
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<p>Resolving this paradox experimentally was not an easy task. After all, how can one show the entanglement of dials within the cell? <a href="https://doi.org/10.1126/science.abm4774">In our recent study</a>, we tackled this challenge by systematically trying out every possible combination of 10 key beneficial mutations and looking at how they affect the growth of cells.</p>
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Read more:
<a href="https://theconversation.com/human-genome-editing-offers-tantalizing-possibilities-but-without-clear-guidelines-many-ethical-questions-still-remain-200983">Human genome editing offers tantalizing possibilities – but without clear guidelines, many ethical questions still remain</a>
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<p>By testing out combinations of mutations, we were able to reliably understand which mutations were entangled together (this entanglement is known as epistasis) and for just 10 mutations, over 1,000 combinations had to be generated.</p>
<h2>How this affects genetic precision medicine</h2>
<p>Current futuristic technologies tout the ability to generate precise single mutations within our own genomes with the hope that this can be used to repair non-functional genetic variants. For example, <a href="https://doi.org/10.1038/s41586-019-1711-4">prime editing</a> is an effective “search-and-replace” genome editing technology.</p>
<p>One important concern with these approaches is they can introduce undesired mutations at the same time. However, even as scientists solve these concerns, the field of human genetics has often <a href="https://doi.org/10.1038/s41576-019-0127-1">overlooked the importance of the interconnectedness of genes</a>.</p>
<p>Our study demonstrates that bioengineers should think not only about the effect a mutation has on the gene it is in, but also about the effect of the mutation in the context of all other variations in our genomes. Altering the function of any of our genes can affect our interconnected cellular networks. </p>
<p>This is compounded by the fact that all of us carry hundreds of extremely rare variants, which means each of us carries a unique interconnected network of genes. These personalized networks make us who we are. </p>
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Read more:
<a href="https://theconversation.com/somatic-genome-editing-therapies-are-becoming-a-reality-but-debate-over-ethics-equitable-access-and-governance-continue-201234">Somatic genome editing therapies are becoming a reality – but debate over ethics, equitable access and governance continue</a>
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<p>Genome interpretation is at the heart of genetic testing for disease. And while scientists have made some progress in identifying key pathogenic genetic variants (those that can cause disease), our findings demonstrate that classifying a variant as pathogenic or benign requires us to also understand how the other genetic dials in our cells are tuned.</p><img src="https://counter.theconversation.com/content/184723/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alex Nguyen Ba receives funding from the Natural Sciences and Engineering Research Council of Canada. </span></em></p>New research sheds light on the interconnected nature of the human genome and what this means for future gene therapies.Alex Nguyen Ba, Assistant Professor, Biology, University of TorontoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1992662023-04-23T14:54:08Z2023-04-23T14:54:08ZDoes our DNA really determine our intelligence and health?<p>In a recent article <a href="https://www.nature.com/articles/s41588-022-01242-5">from Nature Genetics_</a>, scientists raise concerns over the social impacts of recent advances in genomics - i.e. the study of genomes, or in other words, the genetic material of an individual or species. In passages bringing to mind the <a href="https://www.youtube.com/watch?v=W_KruQhfvW4">dystopian sci-fi film <em>Gattaca</em></a>, they describe a near future in which one’s DNA could foretell one’s physical and intellectual abilities and near-perfect children be conceived <em>in vitro</em>.</p>
<p>Indeed, on the surface, it would appear reality is catching up with fiction. We now live in a world where it is now possible to look at the entire genome in a bid to identify the genetic causes of complex diseases. Recent research in genome-wide association studies (GWAS) claims to have pinned down the genetic variants responsible for developing diseases or traits such as drug addiction, antisocial behaviour or intellectual aptitudes.</p>
<p>However, these views are flawed because they are based on a series of errors and misunderstandings; we will now proceed to unpacking them. </p>
<h2>What is a GWAS?</h2>
<p>GWAS seek to highlight differences in allele frequency of markers depending on the expression of the studied trait. The markers can be considered as small flags planted along the genome, each flag having two possible colours (the alleles). The idea behind GWAS is that an association between a marker and a trait allows for the detection of genetic factors independently of environmental factors. This can be done both on quantitative traits (such as height) and diseases.</p>
<p>In the latter case, scientists compare markers between groups of affected and healthy individuals. Each identified marker is then assigned a coefficient that is supposed to represent the strength of its association with the disease. An overall score - known as the <em>Polygenic Risk Score</em> - is finally calculated to represent the level of risk of developing the disease in question.</p>
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<figcaption><span class="caption">The trailer of the 1997 American dystopian science fiction thriller film, <em>Gattaca</em>.</span></figcaption>
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<h2>A new market</h2>
<p>As early as 2007, companies began selling disease risk predictions based on saliva samples. Located in South San Francisco, the biotech and genomics company 23andMe collected over a million DNA samples before being ordered by the FDA in <a href="https://www.businessinsider.com/fda-sends-warning-letter-to-23andme-2013-11?r=US&IR=T">2013</a> to cease its activities for want of clinical evidence.</p>
<p>23andMe managed to keep its doors open by changing its approach and collecting DNA to map out the geographical origins of people’s ancestors. An important part of these DNAs has been made available to scientific teams, allowing them to perform and publish GWAS on huge samples. Initially carried out on hundreds of individuals, GWAS rapidly expanded to millions of people. In the past fifteen years, many studies have claimed to have detected genetic factors that could predict not only our risk of disease, but also our intellectual abilities or social adaptation.</p>
<p>For example, a 2018 <a href="https://www.nature.com/articles/s41588-018-0152-6">study</a> on the educational achievements of nearly 270,000 individuals said it had identified more than a thousand genetic factors responsible for “intelligence”. Four years later, a study based on <a href="https://www.nature.com/articles/s41588-022-01016-z">3 million individuals</a> found the number of genetic factors multiplied by 4. In this spirit, a simple DNA swab would be enough to predict the number of years we were destined to study or <a href="https://www.nature.com/articles/s41586-022-05477-4">whether we would end up as serial smokers or alcoholics</a>.</p>
<h2>The mistaken assumptions behind Polygenic Risk Scores</h2>
<p>The problem is that these conclusions are based on erroneous assumptions and misinterpretation of associations between the traits to be predicted and genetic markers.</p>
<p>Indeed, Polygenic Risk Scores are specifically based on assumptions put forward in 1965 by <a href="https://onlinelibrary.wiley.com/doi/10.1111/j.1469-1809.1965.tb00500.x">Douglas Scott Falconer</a>. Among these hypotheses, it is excluded from the outset that an environmental factor can play an important role in the expression of the trait, even though we know how much lifestyle choices can impact our health. Environmental factors are also thought to impact the individual at random - regardless of their family, social and professional conditions. Last but not least, it is assumed that the pathological processes at the root of the disease are the same for all, when we know that all diseases are very heterogeneous.</p>
<h2>Misinterpretations of the GWAS studies</h2>
<p>Another problem is that Polygenic Risk Scores are based on a flawed interpretation of the GWAS studies. For if the link between a trait and genetic marker could indeed indicate a genetic factor, this remains to be confirmed by subsequent family and functional studies. Associations could just as well reflect environmental or cultural factors.</p>
<p>For example, a GWAS study comparing people in France who consume salted butter with those who consume unsalted butter would show a large number of genetic markers associated with this trait. Not because it would reveal genetic factors conferring a particular taste for salted butter, but because these markers differ between Brittany and other French regions. The problem of interpreting associations also arises for traits that are due to complex interactions between genetic and environmental factors. For example, associations observed between markers and body mass index (BMI) may reflect sociocultural differences, particularly differences in eating habits. This will also be the case for all diseases associated with BMI (diabetes, cardiovascular diseases, breast cancer etc.).</p>
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<img alt="" src="https://images.theconversation.com/files/507620/original/file-20230201-14-eonm5f.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/507620/original/file-20230201-14-eonm5f.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=259&fit=crop&dpr=1 600w, https://images.theconversation.com/files/507620/original/file-20230201-14-eonm5f.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=259&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/507620/original/file-20230201-14-eonm5f.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=259&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/507620/original/file-20230201-14-eonm5f.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=326&fit=crop&dpr=1 754w, https://images.theconversation.com/files/507620/original/file-20230201-14-eonm5f.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=326&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/507620/original/file-20230201-14-eonm5f.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=326&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Example of a graphical representation of a GWAS study of kidney stones.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Manhattan_plot_from_a_GWAS_of_kidney_stone_disease.png">Sarah A. Howles/Wikipedia</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>These false conclusions have serious consequences, as clinicians increasingly turn to risk calculation tools based on these scores.</p>
<h2>Sociological consequences</h2>
<p><a href="https://www.science.org/doi/10.1126/science.1198102">Already denounced in 1975 by Marcus Feldman and Richard Lewontin</a> and in 1978 <a href="https://eudml.org/doc/198864">by Albert Jacquard</a>, the fanciful interpretations of the Intelligence Quotient (IQ) have resurfaced with the idea that your IQ can be predicted from birth based on your DNA.</p>
<p>The IQ variable was originally thought out as a tool to measure the adequacy of a child to a given school programme. It is not a universal and timeless measure of cognitive abilities, or even of intelligence. Even if we restrict ourselves to France, we cannot compare the mental arithmetic performance of children aged 9 today with those of a century ago, for the simple reason that they were not trained in the same way.</p>
<p>Unfortunately, many so-called “socio-genomic” studies are advancing the idea that we are genetically predetermined to perform well or poorly in school. These ideas are widely disseminated by the scientific press, the mainstream media and books by psychologists such as <a href="https://press.princeton.edu/books/hardcover/9780691190808/the-genetic-lottery">Paige Harden</a> and <a href="https://mitpress.mit.edu/9780262039161/blueprint/">Plomin</a>. In light of these ideas, we would be forgiven for asking ourselves about the point of promoting education for all when some are, so to speak, “genetically impervious”.</p>
<h2>Ethical implications</h2>
<p>Polygenic scores are also used by some to differentiate populations according to traits such as intelligence, thereby justifying racist views or eugenic behaviour.</p>
<p>For example, in the <a href="https://www.sciencedirect.com/science/article/abs/pii/S0160289615001087">journal “Intelligence ”</a> , after comparing IQ score of different geographical areas, the author concluded that the genetic factors contributing to intelligence had been subjected to selection pressure during migration and would explain a higher intelligence in the European population than in the African population.</p>
<p>In his presidential address to the American Society of Human Genetics in 2015 [https://pubmed.ncbi.nlm.nih.gov/26942276/ref], geneticist Neil Risch mischievously commented the approach and conclusions. He calculated the scores of Craig Venter (pioneer of human genome sequencing) and James Watson (co-discoverer of the DNA structure). The result was that both have a score below the European average. Risch humorously concluded that a below-average score was enough to land a Nobel Prize or the Medal of Science.</p>
<h2>A flawed genetic model</h2>
<p>In addition to Nature Genetics, journals such as <a href="https://gwern.net/doc/genetics/selection/artificial/2023-meyer.pdf">Science</a>, or <a href="https://www.ashg.org/">societies devoted to human genetics</a> appear rightly concerned about the slippery slope toward genetic determinism we find ourselves on. But they merely raise ethical issues, failing to stress, in the process, that the root of the problem remains an inappropriate genetic model and the misinterpretation of associations with genetic markers.</p>
<p>It would be easy to caricature the scientific debate by labelling those who question the validity of genetic predictions as ‘environmentalists’. Yet to deny the validity of genetic predictions of complex traits is not to deny the effect of genetic factors on these traits. Rather, it is to <a href="https://www.mdpi.com/2075-4426/12/8/1266">challenge the assumptions on which these predictions are based</a>.</p>
<p>On a more positive note, these concerning developments should not obscure the valuable contribution of these new technologies when deployed correctly. In particular, studies described as “ post-GWAS ” have made it possible to highlight the role of certain genes or gene networks in diseases whose causes remain difficult to pin down <a href="https://pubmed.ncbi.nlm.nih.gov/34689168/">(cancers, neurological diseases…)</a>.</p><img src="https://counter.theconversation.com/content/199266/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Les auteurs ne travaillent pas, ne conseillent pas, ne possèdent pas de parts, ne reçoivent pas de fonds d'une organisation qui pourrait tirer profit de cet article, et n'ont déclaré aucune autre affiliation que leur organisme de recherche.</span></em></p>New genetic studies claim to be able to foretell our intelligence or predisposition to certain diseases. But two scientists beg to disagree, reminding us that not everything is written in our DNA.Françoise Clerget-Darpoux, Directeur de recherches émérite en génétique statistique, InsermEmmanuelle Genin, Directrice de Recherche en génétique statistique et des populations, InsermLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2024902023-04-14T12:31:04Z2023-04-14T12:31:04ZDNA study opens a window into African civilisations that left a lasting legacy<figure><img src="https://images.theconversation.com/files/519034/original/file-20230403-14-m699gl.jpg?ixlib=rb-1.1.0&rect=9%2C0%2C6473%2C4325&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Stone obelisks stand tall in Aksum, Ethiopia. This city was once the capital of a kingdom spanning northeast Africa and the Arabian peninsula.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/ancient-monolith-stone-obelisk-symbol-old-1831447870">Shutterstock / Artist</a></span></figcaption></figure><p>Pre-colonial African history is alive with tales of civilisations rising and falling and of different cultures intermingling across the continent. We have now shed more light on some of these societies using the science of genetics. </p>
<p>In a study <a href="https://www.science.org/doi/10.1126/sciadv.abq2616">published in Science Advances</a>, my co-authors and I used DNA information from people from the present-day continent to shed light on important civilisations that existed before colonialism. Genetic information from cheek swabs was extracted by machines. Once the sequence of “letters” in the DNA code had been read, or sequenced, we could use computers to compare genetic differences and similarities between the populations in the study.</p>
<p>One striking result concerned two ethnic groups in the north of present-day Cameroon, in west-central Africa, the Kanuri and Kotoko peoples. We found that these two groups were descended from three ancestral populations. </p>
<p>These ancestral groups most resembled people now living in coastal regions of west Africa as well as in parts of east Africa such as Ethiopia and populations living today in north Africa and the Levant. The populations intermixed – had children together – roughly 600 years ago. But what caused them to migrate thousands of kilometres across a desert into northern Cameroon? </p>
<figure class="align-left ">
<img alt="Map of the Kanem-Bornu empire" src="https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=615&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=615&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=615&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=773&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=773&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519336/original/file-20230404-28-zarx0t.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=773&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The Kanem-Bornu empire at its greatest extent.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Afrika-Kanem-Bornu.png">Tourbillon / Wikipedia Project</a></span>
</figcaption>
</figure>
<p>We think the answer is the <a href="https://www.vincenthiribarren.com/pdf/Hiribarren_-_2016_-_Kanem-Bornu.pdf">Kanem-Bornu empire</a>, a civilisation that existed for over 1,000 years – beginning around 700 AD. At its height, the empire spanned what is now northern Cameroon, northern Nigeria, Chad, Niger and southern Libya. It operated vast trade networks across the Sahara and attracted populations from every direction.</p>
<p>This example highlights how our genomes hold information about major events of the past. Merchants travelling along trade routes or the formation of empires from smaller political units can leave footprints in our DNA. <a href="https://www.science.org/doi/full/10.1126/science.1243518">Previous work</a> <a href="https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1001373">shows</a> that <a href="https://www.science.org/doi/10.1126/science.aay6826">the Roman empire</a>, the <a href="https://www.frontiersin.org/articles/10.3389/fgene.2021.735786/full">Mongol empire</a>, and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267745/">Silk Road trade</a> probably all left lasting legacies in the genomes of modern-day people across Eurasia.</p>
<h2>Hidden in the genome</h2>
<p>We analysed 1,300 newly collected genomes of people from across Africa. They came from 150 ethnic groups within five countries. We collaborated with anthropologists, archaeologists and linguists from Africa and elsewhere. They helped us understand the historical context of these events.</p>
<figure class="align-center ">
<img alt="Mandara mountains" src="https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=360&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=360&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=360&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=452&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=452&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519315/original/file-20230404-982-x059iv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=452&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The Kotoko and Kanuri people live in northern Cameroon and Nigeria. The photo shows a landscape in the Mandara mountains, near the border of the two countries.</span>
<span class="attribution"><span class="source">Scott MacEachern</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>African genome data <a href="https://www.annualreviews.org/doi/10.1146/annurev-biodatasci-102920-%20112550?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed">is underrepresented</a> compared with that from other world regions. This means that lots of genetic diversity – or variety – in the DNA of populations is probably being missed by scientists. </p>
<p>Studying genetic diversity has many potential uses – such as understanding risks to health and developing new treatments for disease. Our group was concerned with genetic diversity as a window into the past.</p>
<h2>Dating events</h2>
<p>We modelled a person’s genome as a mixture of segments of DNA inherited from their ancestors. If a person had DNA segments closely matching two groups of people – for example, Europeans and west Africans – it suggested that this person descended from mixing between those two groups. </p>
<figure class="align-center ">
<img alt="Great Zimbabwe" src="https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519299/original/file-20230404-20-1aikqn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Mysteries remain about other civilisations not studied in the latest work. These are buildings from Great Zimbabwe, a medieval city in Southern Africa.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/great-zimbabwe-medieval-city-southeastern-hills-1048631507">evenfh / Shutterstock</a></span>
</figcaption>
</figure>
<p>Present-day human groups that were formed from a recent mixture of Europeans and west Africans should have long sections of DNA from both populations. Those ancestral DNA segments get shorter as the genetic material of their descendants is shuffled with each new generation. </p>
<p>This provides a way of dating when mixture events took place. The longer the DNA segments matching, for example, west Africans or Europeans, the more recent the mixture event was.</p>
<h2>Peace treaty</h2>
<p>Another historical event we found evidence for was the Arab expansion in Africa. This began in the seventh century, when separate Arab armies travelling south along the Levantine coast and north from Medina in today’s Saudi Arabia crossed the Sinai desert and conquered Egypt.</p>
<figure class="align-left ">
<img alt="The kingdom of Makuria at its peak around 960 AD." src="https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1255&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1255&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1255&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1577&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1577&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519342/original/file-20230404-20-2sx8ay.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1577&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The kingdom of Makuria at its peak around 960 AD.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:The_Kingdom_of_Makuria_at_its_peak.jpg">Le Gabrie</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>In Sudan at this time, the Kingdom of Makuria <a href="http://nubianmonasteries.uw.edu.pl/about/">ruled along the Nile river</a>. Makuria signed a peace treaty with the Egyptian Arabs in the <a href="https://bmcr.brynmawr.edu/2003/2003.01.16/">middle of the seventh century</a> that lasted almost 700 years.</p>
<p>The majority of mixing between these two ancestral groups, one closely related to Arabs and the other to Sudanese, dates to after the peace treaty began breaking down. This in turn coincided with the decline and eventual collapse of Makuria itself, which would have allowed Arab groups to continue down the Nile into Sudan. </p>
<p>But we also found evidence of earlier migrations into Africa from the Arabian peninsula, which occurred by sea. This intermixing coincided in time with the <a href="https://education.nationalgeographic.org/resource/kingdom-aksum/">Kingdom of Aksum</a>, located in northeast Africa and southern Arabia, during the first millennium AD.</p>
<figure class="align-center ">
<img alt="The throne hall of Old Dongola in Sudan, capital of the Makuria kingdom" src="https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1131&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1131&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519067/original/file-20230403-20-eo26qk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1131&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The throne hall of Old Dongola in Sudan, capital of the Makuria kingdom.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/throne-hall-building-old-dongola-deserted-2118567158">Matyas Rehak / Shutterstock</a></span>
</figcaption>
</figure>
<p>Aksum was once considered <a href="https://link.springer.com/chapter/10.1007/978-1-137-11786-%201_2#:%7E:text=The%20Persian%20prophet%20Mani%2C%20who,the%20kingdom%20of%20the%20Chi%20nese.">one of the world’s four great powers</a>, alongside contemporary empires in China, Persia and Rome.</p>
<figure class="align-center ">
<img alt="Map of the Kingdom of Aksum." src="https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=540&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=540&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=540&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=679&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=679&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519565/original/file-20230405-26-hndwxk.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=679&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Map of the Kingdom of Aksum.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Kingdom_of_Aksum_Map.png">Newslea Staff / Wikipedia</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>The expansion of Bantu-speaking peoples</h2>
<p>Genetic studies have also found evidence of a continent-wide migration known as the expansion of Bantu-speaking peoples. “Bantu” is a language group, now spoken by around <a href="https://www.britannica.com/art/Bantu-languages">one-quarter of Africans</a>.</p>
<p>There has been debate about whether the Bantu languages spread largely as a transmission of culture, or whether large-scale migration was involved. The latest research shows that the latter explanation is the likeliest. This migration started in a small area of western Cameroon roughly 4,000 years ago, before rapidly spreading south and east. It covered more than 4,000 kilometres in less than 2,000 years. </p>
<p>Bantu speakers mixed with local groups, <a href="https://www.science.org/doi/full/10.1126/science.aal1988">changing patterns of genetic diversity in Africa</a> forever. We showed that migrations not only occurred to the south and east of Cameroon, but also to the west. Why so much movement took place at this time is unknown, but climate change may have played a role.</p>
<p>It’s vital that scientists analyse more DNA from genomes of African people. As we do so, it will undoubtedly reveal an intricate picture of the continent’s rich past.</p><img src="https://counter.theconversation.com/content/202490/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nancy Bird receives funding from NERC. </span></em></p>DNA analysis sheds light on important societies within Africa that existed before colonialism.Nancy Bird, Postdoctoral research associate, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2024402023-03-23T11:27:11Z2023-03-23T11:27:11ZWe used DNA from Beethoven’s hair to shed light on his poor health – and stumbled upon a family secret<figure><img src="https://images.theconversation.com/files/517132/original/file-20230323-28-r65l6y.jpeg?ixlib=rb-1.1.0&rect=54%2C0%2C4582%2C3717&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Kevin Brown</span>, <span class="license">Author provided</span></span></figcaption></figure><p>Many astonishingly creative people have lived lives cut tragically short by illness. Johannes Vermeer, Wolfgang Amadeus Mozart, Jane Austen, Franz Schubert and Emily Brontë are some famous examples. </p>
<p>Ludwig van Beethoven’s life was not quite as short; he was 56 when he died in 1827. Yet it was short enough to tantalise us as to what more he might have achieved, had he had better health.</p>
<p>For much of his adult life, Beethoven was frequently tormented by pain and poor health – not to mention hearing loss. He gave anguished thought to these afflictions, especially his hearing loss, and <a href="https://www.labonline.com.au/content/life-scientist/article/beethoven-s-genome-sheds-light-on-health-and-history-248507668">hoped they would</a> one day be understood and the explanation made public.</p>
<p>At times he despaired and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071597/">contemplated suicide</a>; at times he stopped composing altogether.</p>
<p>Entire books have been written on Beethoven’s health, based on records from the time. However, my colleagues and I approached the topic from a different perspective. We asked what clues Beethoven’s genome – his DNA – might provide.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/517133/original/file-20230323-22-smm40f.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/517133/original/file-20230323-22-smm40f.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/517133/original/file-20230323-22-smm40f.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=722&fit=crop&dpr=1 600w, https://images.theconversation.com/files/517133/original/file-20230323-22-smm40f.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=722&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/517133/original/file-20230323-22-smm40f.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=722&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/517133/original/file-20230323-22-smm40f.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=907&fit=crop&dpr=1 754w, https://images.theconversation.com/files/517133/original/file-20230323-22-smm40f.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=907&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/517133/original/file-20230323-22-smm40f.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=907&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Beethoven lived from 1770 to 1827.</span>
<span class="attribution"><span class="source">Wikimedia</span></span>
</figcaption>
</figure>
<p>We found some answers, and some surprises, as we explain in new research published in <a href="https://doi.org/10.1016/j.cub.2023.02.041">Current Biology</a>.</p>
<h2>Planting the seed</h2>
<p>Our multinational collaboration began with <a href="https://www.clarehall.cam.ac.uk/news/beethovengenome23/">Tristan Begg</a> – a Beethoven enthusiast and student of biological anthropology, then at the University of California Santa Cruz. </p>
<p>While volunteering at the Ira F. Brilliant Center for Beethoven Studies at San José State University, Begg encountered the centre’s director at the time, historical musicologist William Meredith.</p>
<p>The seed of the project was sown then, but it took eight years and the input of several other specialists to develop it to the point of being published. All the complex multidisciplinary collaborations notwithstanding, the only person who has worked full-time on the project is Begg himself, now in his final PhD year at the University of Cambridge.</p>
<h2>Where did the DNA come from?</h2>
<p>It’s very challenging to extract and analyse DNA from the remains of a dead person (or other animal) – much more so than from living tissues. Nonetheless, huge technical advances have transformed the field of ancient DNA studies. </p>
<p>Generally, the best DNA sources from human remains include teeth and the <a href="https://en.wikipedia.org/wiki/Petrous_part_of_the_temporal_bone">petrous bone</a> in the skull, but none of Beethoven’s bones or teeth were available to us. </p>
<p>What was available was hair. In Beethoven’s day, it was common to collect locks from famous people or loved ones. Dozens of locks attributed to Beethoven are held in public and private collections.</p>
<p>However, hair without roots is a less tractable source of DNA. This DNA tends to exist in short and sometimes degraded sequences. These have to be painstakingly pieced together, using specialised computer software, to construct as much of a complete genome sequence as possible.</p>
<h2>How do we know the locks are Beethoven’s?</h2>
<p>Our project used samples from eight independently sourced locks attributed to Beethoven. Of these, five yielded DNA from the same male individual, with degrees of damage consistent with origins in the early 19th century. </p>
<p>Working with the ancestry firm FamilyTreeDNA, we traced the ancestry for this person to western-central Europe. We are confident it is Beethoven, since two of the locks exist alongside uninterrupted provenance records going as far back as the 1820s.</p>
<p>Three more locks, genetically identical with the other two, also had good (although not completely uninterrupted) provenance records.</p>
<p>The combination of excellently documented provenances with perfect genetic agreement between five independently sourced samples made it very difficult to doubt these hair samples came from Beethoven.</p>
<p>That left three locks of hair. Two of these were clearly genetically different from the other five: one is a woman’s. We don’t know how these came to be attributed to Beethoven.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/517134/original/file-20230323-16-doyl0m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/517134/original/file-20230323-16-doyl0m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/517134/original/file-20230323-16-doyl0m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=356&fit=crop&dpr=1 600w, https://images.theconversation.com/files/517134/original/file-20230323-16-doyl0m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=356&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/517134/original/file-20230323-16-doyl0m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=356&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/517134/original/file-20230323-16-doyl0m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=447&fit=crop&dpr=1 754w, https://images.theconversation.com/files/517134/original/file-20230323-16-doyl0m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=447&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/517134/original/file-20230323-16-doyl0m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=447&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Our results showed the Hiller lock, previously attributed to Beethoven, actually came from a woman.</span>
<span class="attribution"><span class="source">Ira F. Brilliant Center for Beethoven Studies, San Jose State University / William Meredith</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>One of the misattributions is significant in itself, because it was the basis of <a href="https://www.science.org/content/article/beethoven-dead-lead#">earlier research</a> that concluded Beethoven had been subject to lead poisoning. Our findings show this conclusion no longer stands. </p>
<p>The eighth lock yielded too little DNA to be declared authentic or otherwise.</p>
<h2>What we learnt about Beethoven’s health</h2>
<p>We didn’t expect to find a genetic basis for Beethoven’s most widely known health problem – his hearing loss – and this was borne out. Beethoven had <a href="https://www.pennmedicine.org/for-patients-and-visitors/find-a-program-or-service/ear-nose-and-throat/general-audiology/center-for-adult-onset-hearing-loss#:%7E:text=Adult%2Donset%20hearing%20loss%20is%20a%20form%20of%20progressive%20deafness,educational%20success%2C%20and%20cognitive%20decline.">adult-onset hearing loss</a>, which is only rarely attributable to primarily genetic causes.</p>
<p>He was, however, beset for many years by other health problems – particularly gastrointestinal problems (pain and diarrhoea) and liver disease. </p>
<p>Working with the Bonn University medical genetics team, we didn’t find Beethoven to be especially genetically susceptible to any particular gastrointestinal condition, such as inflammatory bowel disease, irritable bowel syndrome, coeliac disease or lactose intolerance (as some <a href="https://pubmed.ncbi.nlm.nih.gov/16015189/#">have hypothesised</a>). Our main discoveries related to liver disease.</p>
<p>We already knew through documentation that Beethoven had attacks of jaundice. Begg’s work has now shown Beethoven had two copies of a particular variant of the <a href="https://www.journal-of-hepatology.eu/article/S0168-8278(16)30084-8/pdf">PNPLA3 gene</a>, which is linked to liver cirrhosis. He also had single copies of two variants of a gene that causes haemochromatosis, a condition that damages the liver.</p>
<p>Quite remarkably, the analyses also revealed Beethoven was infected with the hepatitis B virus in the final months of his life (and perhaps before). Hepatitis B infection <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/liv.12409">may have been</a> common in Europe at the time, but details on this are scant.</p>
<p>What’s more, alcohol consumption may have exacerbated Beethoven’s liver disease risk. There has been controversy regarding the extent and nature of his alcohol consumption, which is referred to – but not quantified – in surviving records. </p>
<p>Begg reviewed the records carefully and concluded Beethoven’s alcohol consumption was likely unexceptional <a href="https://www.ncbi.nlm.nih.gov/books/NBK524980/">for the time and place</a>, but may have still been at levels now considered harmful.</p>
<h2>Revelations from the Beethoven family</h2>
<p>There was one more surprise in store for us. As part of our work, we sought to link Beethoven’s genome with those of living members of the Beethoven lineage. To do this we focused on the Y chromosome, which is inherited in the male line only (following a similar pattern to surnames in most European traditions). </p>
<p>Five men with the surname Beethoven contributed their DNA samples. They were not closely related to each other, and were living in present-day Belgium where the surname originates. They all essentially shared the same Y chromosome, which could be put down to descent from a common male ancestor: Aert van Beethoven (1535-1609).</p>
<p>The surprise was that Ludwig van Beethoven’s locks had a different Y chromosome. Having considered other explanations, we inferred that at some point in the seven generations between Aert and Ludwig, someone’s father for social and legal purposes was not their biological father. </p>
<p>But we couldn’t decipher, based on the evidence available, which generation this might have been.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/beethoven-250-analysis-of-the-composers-letters-proves-that-creativity-does-spring-forth-from-misery-149771">Beethoven 250: analysis of the composer's letters proves that creativity does spring forth from misery</a>
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</em>
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<h2>What’s next?</h2>
<p>We will be making the genome we sequenced publicly available, as there may be more to discover from further analyses.</p>
<p>Beyond Beethoven, our project is an example of wider possibilities opening up in the field of DNA analysis. It shows meaningful results can be obtained even from such unpromising DNA sources as historical hair locks.</p>
<p>To date, population genetics has seldom taken its analyses down to the level of a single individual. This is hard to do, but we show it’s not impossible.</p>
<p>Who might be next? Perhaps someone else about whom there is a distinct question to answer – or even someone who may themselves have wanted that question answered.</p>
<hr>
<p><em>Acknowledgments: In addition to lead author Tristan Begg (University of Cambridge), I would like to acknowledge all other co-authors including Johannes Krause and Arthur Kocher (Max Planck Institute for Evolutionary Anthropology, Leipzig), Toomas Kivisild and Maarten Larmuseau (KU Leuven), Markus Nöthen and Axel Schmidt (University of Bonn), and all sample donors including philanthropist Kevin Brown.</em></p><img src="https://counter.theconversation.com/content/202440/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>I have been a student (50 years ago) at the University of Cambridge, and more recently a staff member at the University of Cambridge, a departmental colleague of Toomas Kivisild, and a PhD supervisor of Tristan Begg.</span></em></p>Beethoven was afflicted with health conditions for much of his adult life, and wished for their cause to be discovered and made public.Robert Attenborough, Honorary Senior Lecturer in Bioanthropology, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2012342023-03-10T22:42:38Z2023-03-10T22:42:38ZSomatic genome editing therapies are becoming a reality – but debate over ethics, equitable access and governance continue<figure><img src="https://images.theconversation.com/files/514625/original/file-20230310-30-d4sd7f.jpg?ixlib=rb-1.1.0&rect=0%2C51%2C5760%2C3181&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Sangharsh Lohakare / Unsplash</span></span></figcaption></figure><p>Hundreds of experts from around the world gathered at the Francis Crick Institute in London this week for the Third International Summit on Human Genome Editing.</p>
<p>As at the first and second summits, held in Washington DC in 2015 and Hong Kong in 2018, leading experts in research shared their discoveries and discussed how they should be used. </p>
<p>The prospect of curing certain diseases by changing the parts of our DNA that cause them is becoming a reality. A somatic genome editing treatment for sickle cell disease is set to obtain <a href="https://www.barrons.com/articles/crispr-therapeutics-stock-fda-sickle-cell-gene-therapy-bf56a18c">regulatory approval</a> in the US later this year.</p>
<p>“Delivery” was a recurring issue: the delivery of equitable access to genome editing therapies, ongoing research to optimise delivery systems for genome editing apparatus and delivery of measures to foster discussions regarding regulation, governance, public and patient engagement.</p>
<p>American Nobel laureate David Baltimore aptly noted in his opening remarks, “new technologies continue to challenge our society”. The advent of CRISPR gene-editing technology, short for “Clustered Regularly Interspaced Short Palindromic Repeats”, has reaffirmed this proposition, igniting a global dialogue on its accompanying ethical and regulatory issues. </p>
<p>Five years after the last summit, CRISPR technology has continued to mature. It is an insurmountable task to capture all of the developments in both the science and ethics of CRISPR technology. These will be addressed with reference to the key themes raised during the summit – scientific developments, accessibility and the importance of public and patient engagement. </p>
<h2>Scientific developments</h2>
<p>Many new advances in genome editing techniques were presented. </p>
<p>American chemist and biologist David Liu reported on findings to use “<a href="https://www.nature.com/articles/d41587-019-00032-5">prime editing</a>” to treat genetic conditions such as Huntington’s disease and Friedreich’s ataxia. Unlike CRISPR, which makes a double stranded cut in the DNA, prime editing induces a single stranded cut. This makes it more versatile and precise for targeted deletion and insertion of genetic sequences.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-gene-editing-and-how-could-it-shape-our-future-199025">What is gene editing and how could it shape our future?</a>
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</p>
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<p>The summit heard about Vertex Pharmaceutical’s CRISPR-based treatment for sickle cell disease. The treatment is <a href="https://www.statnews.com/2023/03/07/crispr-sickle-cell-access/">expected</a> to become the first approved CRISPR genome editing therapy later this year.</p>
<p>There were also reports of research using CRISPR technology to treat diseases including Duchenne muscular dystrophy, cancer, HIV/AIDS, heart and muscle disease and inborn errors of immunity. American molecular biologist Eric Olson reported success in using base editing to <a href="https://www.science.org/doi/10.1126/science.ade1105">target CaMKIIδ</a>, a central regulator of cardiac signalling, in restoring cardiac function, as a treatment for myocardial infarction. </p>
<h2>Equitable access</h2>
<p>As research proceeds and treatments become available, questions about equitable access to the technology arise.</p>
<p>Equity extends beyond considerations of cost, access and ownership, to research engagement and output. This refers to capacity for knowledge production, data sovereignty and collection, access to latest knowledge, opportunities for collaboration and infrastructure to facilitate recruitment and trialling of new therapies. </p>
<p>Access issues are particularly relevant to lower- and middle-income countries, which may be compromised by systemic and structural inequities. Policy and political landscapes, economic constraints and scientific racism further perpetuate this inequity. </p>
<p>Gautam Dongre, representing the National Alliance of Sickle Cell Organisations India, described the reality of those living with sickle cell disease in India, where access to treatment is dire: </p>
<blockquote>
<p>“Our priority is to be alive, to receive gene therapy in the future.”</p>
</blockquote>
<h2>Patient perspectives and public engagement</h2>
<p>The summit also gave a platform to the experiences and concerns of people with lived experience of genetic disease. This included insights into the role and utility of public engagement, such as patient advocacy groups, do-it-yourself community groups and citizens’ juries.</p>
<p>A memorable presentation from Victoria Gray – the first recipient of Vertex Pharmaceutical’s CRISPR therapy for sickle cell disease – highlighted its life-changing impact. Gray says her CRISPR-modified “super cells” have cured her, enabling her to lead a disease-free life. The great potential of CRISPR technology can be realised, but importantly, it must be accessible to all.</p>
<h2>Concluding remarks</h2>
<p>How should CRISPR technology be regulated? This is a critical question.</p>
<p>As the summit’s organisers <a href="https://royalsociety.org/-/media/events/2023/03/human-genome-editing-summit/statement-from-the-organising-committee-of-the-third-international-summit-on-human-genome-editing.pdf">noted</a>, somatic genome editing has made “remarkable progress”, demonstrating its capability to “cure once-incurable diseases”. Further research is needed to target more diseases and enhance our understanding of risks and unintended consequences.</p>
<p>“Somatic” genome editing (which makes changes that are not heritable) is different to germline and heritable genome editing (which makes heritable changes). </p>
<p>Basic research for germline genome editing, which is not for reproduction purposes, is underway, for example, in gametes and embryos to explore aspects of early development. However, the organising committee concluded that heritable human genome editing for reproduction purposes “remains unacceptable at this time”. This is in light of the absence of preclinical evidence for safety and efficacy, legal authorisation and rigorous oversight and governance.</p>
<p>The concept of “safe enough” was interrogated – whose ethics should be applied to make this value judgment? Does the notion of safety traverse into areas beyond medically defined risks of physical harm? </p>
<p>It is notable that risk tolerance and perception of safety is dictated by an individual’s position in their country, culture, socio-economic status and lived experience. </p>
<p>In 2021, the World Health Organization published <a href="https://www.who.int/publications/i/item/9789240030060">a framework for governing human genome editing</a>. This retains its authority as an exemplar for a pathway toward an appropriate regulatory framework. While not overly prescriptive, it was designed to be adaptable for implementation in any jurisdiction. This year, Uganda plans to implement the framework as a pilot project. </p>
<p>The organising committee called for global action to explore measures for equitable and affordable pathways to access genome editing therapies. Ongoing global discussions are far from complete, and perhaps may never be complete, reinforcing the need for collective dialogue to proceed this summit. <em>And on with research, innovation and collaboration</em>.</p><img src="https://counter.theconversation.com/content/201234/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Olga C. Pandos is a recipient of the Australian Government Research Training Program Scholarship.</span></em></p>At the Third International Summit on Human Genome Editing, experts gather to discuss the path forward for CRISPR and other gene-editing technologiesOlga C. Pandos, PhD Candidate in Technology, Medical Law and Ethics, University of AdelaideLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2009832023-03-08T12:06:26Z2023-03-08T12:06:26ZHuman genome editing offers tantalizing possibilities – but without clear guidelines, many ethical questions still remain<figure><img src="https://images.theconversation.com/files/513790/original/file-20230306-28-k1tc0y.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1936%2C1547&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">DNA editing has the capacity to treat many diseases, but how to do this safely and equitably remains unclear.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/molecules-illustration-royalty-free-image/1148113002">KTSDESIGN/Science Photo Library via Getty Images</a></span></figcaption></figure><p><a href="https://royalsociety.org/science-events-and-lectures/2023/03/2023-human-genome-editing-summit/">The Third International Summit on Human Genome Editing</a>, a three-day conference organized by the Royal Society, the U.K. Academy of Medical Sciences, the U.S. National Academies of Sciences and Medicine and The World Academy of Sciences, was held this week in March 2023 at the Francis Crick Institute in London. Scientists, bioethicists, physicians, patients and others gathered to discuss the latest developments on this technology that lets researchers modify DNA with precision. And a major topic at the summit was <a href="https://royalsociety.org/-/media/events/2023/03/human-genome-editing-summit/third-international-summit-on-human-genome-editing-programme-booklet.pdf?la=en-GB&hash=16DB894FBD02A549B2F090D575C3E92D">how to enforce</a> research policies and ethical principles for human genome editing.</p>
<p>One of the first agenda items was how to regulate human genome editing in China in light of its <a href="https://theconversation.com/crispr-babies-raise-an-uncomfortable-reality-abiding-by-scientific-standards-doesnt-guarantee-ethical-research-108008">misuse in 2018</a>, when scientists modified the DNA of two human embryos before birth to have resistance against HIV infection. The controversy stems from the fact that because the technology is relatively early in its development, and its potential risks have not been reduced or eliminated, editing human embryos in ways they could pass on to their own offspring could lead to a variety of known and unknown adverse complications. The <a href="https://www.statnews.com/2023/03/06/genome-editing-summit-experts-worry-rule-changes-in-china-fall-short/">summit speakers noted</a> that while China has updated its guidelines and laws on human genome editing, it failed to address privately funded research – an issue other countries also face. Many countries, including the U.S., <a href="https://doi.org/10.1038/d41586-023-00625-w">do not have sufficiently robust regulatory frameworks</a> to prevent a repeat of the 2018 scandal.</p>
<p>We are a <a href="https://www.rit.edu/hudsonlab/">biochemist</a> and a <a href="https://www.rit.edu/directory/grssbi-gary-skuse">geneticist</a> who teach and conduct research in genomics and ethics at the Rochester Institute of Technology. As in our classrooms, debate about genome editing continues in the field.</p>
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<figcaption><span class="caption">Listening to different perspectives about CRISPR could lead to more balanced discussions about how to regulate it.</span></figcaption>
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<h2>What is genome editing?</h2>
<p>The <a href="https://theconversation.com/the-human-genome-project-pieced-together-only-92-of-the-dna-now-scientists-have-finally-filled-in-the-remaining-8-176138">human genome</a> typically consists of 23 pairs of chromosomes made of approximately 3.2 billion nucleotides – the building blocks of DNA. There are four nucleotides that make up DNA: adenine (A), thymine (T), guanine (G) and cytosine (C). If the genome were a book, each chromosome would be a chapter, each gene on a particular chromosome would be a paragraph and each paragraph would be made of individual letters (A, T, G or C). </p>
<p>One can imagine a book with over 3 billion characters might need editing to correct mistakes that occurred during the writing or copying processes. </p>
<p>Genome editing is a way for scientists to make specific changes to the DNA in a cell or in an entire organism by adding, removing or swapping in or out one or more nucleotides. In people, these changes can be done in somatic cells, those with DNA that cannot be inherited by offspring, or in gamete cells, those containing DNA that can be passed on to offspring. Genome editing of gamete cells, which includes egg or sperm, is controversial, as any changes would be passed on to descendants. Most <a href="https://doi.org/10.1089/crispr.2020.0082">existing guidelines and policies</a> prohibit its use at this time.</p>
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<figcaption><span class="caption">Geneticist Jennifer Doudna is one of the co-inventors of CRISPR/Cas9.</span></figcaption>
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<h2>How CRISPR works</h2>
<p>In 2012, scientists published a <a href="https://doi.org/10.1126/science.1225829">groundbreaking study</a> demonstrating how CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, can be used to accurately change specific DNA sequences.</p>
<p>CRISPR’s natural origins are as a kind of immune response for bacteria. Bacteria that can be infected with viruses have evolved mechanisms to combat them. When a bacterium is infected with a particular virus, it keeps a small piece of the viral DNA sequence called a “spacer” in its own genome. This spacer is an exact match to the viral DNA. Upon subsequent infection, the bacterium is able to use the spacer to recruit a scissorlike protein called Cas9 that can sever new viral DNA attempting to integrate into the bacterium’s genome. This cut to the genetic material prevents the virus from replicating and killing its bacterial host.</p>
<p>After this discovery, scientists were able to fine-tune the system in the lab to be highly precise. They can sever DNA from a variety of cells, including human cells, at a specific location in the genome and subsequently edit it by adding, removing or swapping nucleotides. This is similar to adding or removing letters and words from a book. </p>
<p>This technology has the potential to treat diseases that have genetic origins. One of the summit’s sessions covered CRISPR’s ongoing experimental use to treat patients with <a href="https://doi.org/10.1056/NEJMoa2031054">sickle cell anemia and beta-thalassemia</a>, two blood disorders caused by mutations in the genes. Notably, genetic modification to treat sickle cell anemia and beta-thalassemia involves editing somatic cells, not germline cells. But as the summit speakers noted, whether these likely expensive therapies will be <a href="https://www.statnews.com/2023/03/07/crispr-sickle-cell-access/">accessible to the people who need them most</a>, especially in low- and middle-income countries, is a problem that requires changes to how treatments are sold.</p>
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<figcaption><span class="caption">Scientists have been testing ways to use CRISPR/Cas9 to treat sickle cell anemia.</span></figcaption>
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<h2>Ethics of human genome editing</h2>
<p><a href="https://doi.org/10.1016%2Fj.jmb.2018.05.044">Many questions remain</a> concerning the safety of genome editing, along with its potential to promote eugenics and exacerbate inequities and inequality.</p>
<p>A number of the summit’s sessions involved discussion on the ethics and regulation of the use of this tool. While the landmark 1979 <a href="https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html">Belmont Report</a> outlined several ethical pillars to guide human research in the U.S., it was published before human genome editing was developed. In 2021, the World Health Organization <a href="https://www.who.int/news/item/12-07-2021-who-issues-new-recommendations-on-human-genome-editing-for-the-advancement-of-public-health">issued recommendations on human genome editing</a> as a tool to advance public health. There is <a href="https://doi.org/10.1146/annurev-genom-111320-091930">no current international law</a> governing human genome editing. </p>
<p>There is <a href="https://www.pewresearch.org/internet/2022/03/17/americans-are-closely-divided-over-editing-a-babys-genes-to-reduce-serious-health-risk/">still a debate</a> regarding how to use this technology. Some people equate genome editing to interfering with the work of God and argue that it shouldn’t be used at all, while others recognize its potential value and weigh that against its potential risks. The latter focuses on the fundamental question of <a href="https://www.scientificamerican.com/article/the-dark-side-of-crispr/">where to draw the line</a> between which applications are considered acceptable and which are not. For example, some people will agree that using genome editing to modify a defective gene that may lead to an infant’s death if untreated is acceptable. But these same people may frown upon the use of genome editing to ensure that an unborn child has specific physical features such as blue eyes or blond hair.</p>
<p>Nor is there consensus about <a href="https://doi.org/10.1001/jama.2022.13468">what diseases</a> are desirable targets. For example, it may be acceptable to modify a gene to prevent an infant’s death but not acceptable to modify one that prevents a disease later in life, such as the gene responsible for <a href="https://www.mayoclinic.org/diseases-conditions/huntingtons-disease/symptoms-causes/syc-20356117">Huntington’s disease</a>.</p>
<p>The potential for positive applications of human genome editing is both numerous and tantalizing. But establishing informed regulatory legislation everyone can agree on is and will continue to be a challenge. Conferences such as the human genome editing summit are one way to continue important discussions and educate the scientific community and the public on the benefits and risks of genome editing.</p><img src="https://counter.theconversation.com/content/200983/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andre Hudson receives funding from the National Institutes of Health</span></em></p><p class="fine-print"><em><span>Gary Skuse has received funding from the National Science Foundation. </span></em></p>Following the controversial births of the first gene-edited babies, a major focus of the Third International Summit on Human Genome Editing was responsible use of CRISPR.André O. Hudson, Interim Dean/Professor-College of Science, Rochester Institute of TechnologyGary Skuse, Professor of Bioinformatics, Rochester Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1972212023-01-05T20:33:11Z2023-01-05T20:33:11ZDNA reveals large migration into Scandinavia during the Viking age<figure><img src="https://images.theconversation.com/files/503216/original/file-20230105-20-c8gnzd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">More people moved into Scandinavia in Viking times than at any other time period analysed in the study.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/old-wooden-viking-snekkja-longship-type-2044280747">Shutterstock</a></span></figcaption></figure><p>We often think of the Vikings as ultimate explorers, taking their culture with them to far-off lands. But we may not typically think of Viking age Scandinavia as a hub for migration from all over Europe.</p>
<p><a href="https://www.cell.com/cell/fulltext/S0092-8674(22)01468-4">In a study published in Cell</a>, we show this is exactly what happened. The Viking period (late 8th century to mid 11th century) was the catalyst for an exceptional inflow of people into Scandinavia. These movements were greater than for any other period we analysed.</p>
<p>What’s also striking is that later Scandinavians don’t show the same high levels of non-local ancestry present in their Viking-era counterparts. We don’t completely understand why the migrants’ genetic impact was reduced in later Scandinavians, but there are some possibilities.</p>
<p>We analysed genomes (the full complement of DNA contained in human cells) from around 17,000 Scandinavian individuals, including nearly 300 from ancient burials. We combined <a href="https://www.sciencedirect.com/science/article/pii/S0960982218308443">existing datasets</a> with new samples. These were analysed together in a dataset spanning 2,000 years.</p>
<p>We used these genomes to explore when people arrived in the region from outside and where they came from. New DNA samples were collected from several iconic Swedish archaeological sites. </p>
<p>These included Sandby borg, which is a “ring fortress” <a href="https://www.cambridge.org/core/journals/antiquity/article/moment-frozen-in-time-evidence-of-a-late-fifthcentury-massacre-at-sandby-borg/5C803B7E77A41439BC3B50D4BF96560E">where a massacre occurred just before 500 AD</a>, and the Vendel cemetery, which features several burials contained in large boats and dating to between the 6th and 8th centuries AD. We also used samples from Viking chamber burials and remains from Kronan, a <a href="https://www.tandfonline.com/doi/abs/10.1111/j.1095-9270.1990.tb00276.x">warship that capsized with more than 800 men</a> in 1676.</p>
<p>Two previous studies <a href="https://www.sciencedirect.com/science/article/pii/S0960982218308443">noted extensive migration</a> into Scandinavia <a href="https://www.nature.com/articles/s41586-020-2688-8">during the Viking age</a>. But in our latest study, we have clarified some of the details about this flow of genes into the region.</p>
<p>We found that movements of people from western Europe impacted all of Scandinavia, while migration from the east was more localised, with peaks in the Lake Mälaren Valley and Gotland. Finally, gene flow from southern Europe largely affected the south of Scandinavia. </p>
<p>Since the study was based on a 2,000-year chronology, it was not only possible to see there was an increase in migration during the Viking era, but also that it starts to fall with the onset of the medieval period.</p>
<p>The non-local ancestry that arrives in the region at this time falls away in later periods. Much of the genetic influence from eastern Europe disappears and the western and southern influence becomes significantly diluted. The best way to explain this is that people who arrived in Scandinavia during Viking times did not have as many children as the people who were already living there.</p>
<p>There are different possible reasons for this. The migrants could have belonged to groups that did not intend to settle down in Scandinavia, instead aiming to return to where they came from. Tradespeople and diplomats are examples in this category. Additionally, the migrants could also have belonged to groups that were not allowed to have families or children, such as slaves and priests.</p>
<p>We also looked at influences that began at earlier periods in time. For example, the DNA of modern Scandinavians <a href="https://www.nature.com/articles/s41431-021-00899-6">changes gradually as you travel from north to south</a>. This genetic “cline”, or gradient, is due to migrations into the region of people carrying shared genetic similarities known as the Uralic component.</p>
<p>Modern examples of where the Uralic genetic component can be found are among Sami people, people in modern Finland, some Native Americans and some central Asian groups. </p>
<p>In our dataset, we found occasional instances of people with Uralic ancestry – mainly in northern Scandinavia – during the Viking period and medieval times. But the Uralic influence seems to increase after this time, since individuals from our 17th century sample have similar levels of this ancestry to people living today.</p>
<p>There were many other fascinating stories from our study. For example, at the Viking age burial site of Sala, by the river Sagån, we find a woman that seems to be fully British or Irish in her genomic composition. This woman was buried in a prestigious Viking period boat burial. We don’t know exactly what position she held in society, but she would not have been a slave or a priest. </p>
<p>Among the individuals found on the wreck of the Kronan, there were two people who came from what is now Finland and another who has a genetic affinity with people from the Baltic states, such as Lithuania and Latvia (though this identification is not conclusive). At the time of the Kronan incident in 1676, these areas were part of the Swedish Empire, though they are independent today.</p>
<p>The work sheds more light on the historical events that shaped the populations of Scandinavia over time. The Viking age was marked by Scandinavians’ curiosity of the world outside their home region. But, from our results, it also appears that the world outside this region was curious enough about the Vikings to travel to Scandinavia.</p><img src="https://counter.theconversation.com/content/197221/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anders Götherström receives funding from VR, KVA, and EU. </span></em></p><p class="fine-print"><em><span>Ricardo Rodriguez Varela does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>DNA analysis reveals a large migration of people into Scandinavia during Viking times.Anders Götherström, Professor in Molecular Archaeology, Department of Archaeology and Classical Studies, Stockholm UniversityRicardo Rodriguez Varela, Research in Molecular Archaeology, Department of Archaeology and Classical Studies, Stockholm University, Stockholm UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1947932022-11-21T13:15:49Z2022-11-21T13:15:49ZPeople don’t mate randomly – but the flawed assumption that they do is an essential part of many studies linking genes to diseases and traits<figure><img src="https://images.theconversation.com/files/496010/original/file-20221117-25-slwoe3.jpg?ixlib=rb-1.1.0&rect=110%2C96%2C4690%2C2134&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Statistical pitfalls in GWAS can result in misleading conclusions about whether some traits (like long horns or spotted skin, in the case of dinosaurs) are genetically linked.</span> <span class="attribution"><span class="source">@meanymoo</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><p>The idea that <a href="https://doi.org/10.1002/0471667196.ess0209.pub2">correlation does not imply causation</a> is a fundamental caveat in epidemiological research. A classic example involves a hypothetical link between ice cream sales and drownings – instead of increased ice cream consumption causing more people to drown, it’s plausible that a third variable, summer weather, is driving up an appetite for ice cream and swimming, and hence opportunities to drown.</p>
<p>But what about correlations involving genes? How can researchers be sure that a particular trait or disease is truly genetically linked, and not caused by something else?</p>
<p>We are <a href="https://www.richardborder.com">statistical</a> <a href="https://scholar.google.com/citations?user=SPXgieEAAAAJ&hl=en">geneticists</a> who study the genetic and nongenetic factors that influence human variation. In our <a href="https://www.science.org/doi/10.1126/science.abo2059">recently published research</a>, we found that the genetic links between traits found in many studies might not be connected by genes at all. Instead, many are a result of how humans mate.</p>
<h2>Genome-wide association studies try to link genes to traits</h2>
<p>Because the genes you inherit from your parents remain unchanged throughout your life, with rare exception, it makes sense to assume that there is a causal relationship between certain traits you have and your genetics.</p>
<p>This logic is the basis for <a href="https://www.genome.gov/about-genomics/fact-sheets/Genome-Wide-Association-Studies-Fact-Sheet">genome-wide association studies, or GWAS</a>. These studies collect DNA from many people to identify positions in the genome that might be correlated with a trait of interest. For example, if you have certain forms of the <a href="https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet"><em>BRCA1</em> and <em>BRCA2</em> genes</a>, you may have an increased risk for certain types of cancer.</p>
<p>Similarly, there may be gene variants that play a role in whether or not someone has schizophrenia. The hope is to learn something about the complex mechanisms that link variation at the molecular level to individual differences. With a clearer understanding of the genetic basis of different traits, scientists would be better able to determine risk factors for related diseases. </p>
<figure>
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<figcaption><span class="caption">GWAS studies seek to find genetic associations between individual traits.</span></figcaption>
</figure>
<p>Researchers have run <a href="https://doi.org/10.1093/nar/gky1120">thousands of GWAS to date</a>, identifying genetic variants associated with myriad diseases and disease-related traits. In many instances, researchers have identified genetic variants that affect more than one trait. This form of biological overlap, in which the same genes are thought to influence several apparently unrelated traits, is known as <a href="https://doi.org/10.1186/s13073-016-0332-x">pleiotropy</a>. For example, certain variants of the <a href="https://medlineplus.gov/genetics/gene/pah"><em>PAH</em> gene</a> can have <a href="https://medlineplus.gov/genetics/condition/phenylketonuria/">several distinct effects</a>, including altering skin pigmentation and causing seizures.</p>
<p>One way scientists assess pleiotropy is through <a href="https://doi.org/10.1038/ng.3604">genetic correlation analysis</a>. Here, geneticists investigate whether the genes associated with a given trait are associated with other traits or diseases by statistically analyzing large samples of genetic data. Over the past decade, genetic correlation analysis has become the primary method for assessing potential pleiotropy across fields as diverse as <a href="https://doi.org/10.1038/ng.3406">internal medicine</a>, <a href="https://www.thessgac.org">social science</a> and <a href="https://doi.org/10.1017/s0033291717002318">psychiatry</a>. </p>
<p>Scientists use the findings from genetic correlation analyses to figure out the potential shared causes of these traits. For instance, if <a href="https://doi.org/10.1126/science.aap8757">genes associated with bipolar disorders</a> also predict anxiety disorders, perhaps the two conditions may partially involve some of the same neural circuits or respond to similar treatments.</p>
<h2>Assortative mating and genetic correlation</h2>
<p>However, just because a gene is correlated with two or more traits doesn’t necessarily mean it causes them.</p>
<p>Virtually all the statistical methods researchers commonly use to assess genetic correlations <a href="https://doi.org/10.1046/j.1439-0388.2002.00356.x">assume that mating is random</a>. That is, they assume that potential mating partners decide who they will have children with based on a roll of the dice. In reality, many factors likely influence who mates with whom. The simplest example of this is geography – people living in different parts of the world are less likely to end up together than people living nearby.</p>
<p>We wanted to find out how much the assumption of random mating affects the accuracy of genetic correlation analyses. In particular, we focused on the potential confounding effects of <a href="https://doi.org/10.1038/s41562-018-0476-3">assortative mating</a>, or how people tend to mate with those who share similar characteristics with them. Assortative mating is a widely documented phenomenon seen across a broad array of traits, interests, measures and social factors, including <a href="https://doi.org/10.1002/ajhb.22917">height</a>, <a href="https://doi.org/10.2307/2095670">education</a> and <a href="https://doi.org/10.1016/j.biopsych.2019.06.025">psychiatric conditions</a>.</p>
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<figcaption><span class="caption">Humans do not mate randomly – rather, people tend to gravitate toward certain traits.</span></figcaption>
</figure>
<p>In <a href="https://doi.org/10.1126/science.abo2059">our study</a> we examined cross-trait assortative mating, whereby people with one trait (for example, being tall) tend to mate with people with a completely different trait (for example, being wealthy). From our database of 413,980 mate pairs in the U.K. and Denmark, we found evidence of cross-trait assortative mating for many traits – for instance, an individual’s time spent in formal schooling was correlated not only with their mate’s educational attainment, but also with many other characteristics, including height, smoking behaviors and risk for different diseases.</p>
<p>We found that taking into consideration the similarities across mates could strongly predict which traits would be considered genetically linked. In other words, just based on how many characteristics a pair of mates shared, we could identify around 75% of the presumed genetic links between these traits – all without sampling any DNA.</p>
<h2>Genetic correlation does not imply causation</h2>
<p>Cross-trait assortative mating shapes the genome. If people with one heritable trait tend to mate with people with another heritable trait, then these two distinct characteristics will become genetically correlated to each other in subsequent generations. This will happen regardless of whether or not these traits are truly genetically linked to each other.</p>
<p>Cross-trait assortative mating means that the genes you inherit from one parent will be correlated with those you inherit from the other. How people mate is not random, violating the key assumption behind genetic correlation analyses. This inflates the genetic association between traits that aren’t truly linked together by genes.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of dinosaurs with and without long horns or spiked backs." src="https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=424&fit=crop&dpr=1 600w, https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=424&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=424&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=533&fit=crop&dpr=1 754w, https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=533&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/495756/original/file-20221116-21-hyom6p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=533&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">If dinosaurs with long horns preferentially mate with dinosaurs with spiked backs, genes for both of these traits can become associated with each other in subsequent generations even though the same gene doesn’t code for them.</span>
<span class="attribution"><span class="source">Aaqilah M</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Recent studies corroborate our findings. Earlier this year, researchers computed genetic correlations using a method that examines the association between the <a href="https://doi.org/10.1038/s41588-022-01062-7">traits and genes of siblings</a>. The genetic links between traits influenced by cross-trait assortative mating were substantially weakened.</p>
<p>But without accounting for cross-trait assortative mating, using genetic correlation estimates to study the biological pathways causing disease can be misleading. Genes that affect only one trait will appear to influence multiple different conditions. For example, a genetic test designed to assess the risk for one disease may incorrectly detect vulnerability for a broad number of unrelated conditions.</p>
<p>The ability to measure variation across individuals at the genetic and molecular level is truly a feat of modern science. However, genetic epidemiology is still an observational enterprise, subject to the same caveats and challenges facing other forms of nonexperimental research. Though our findings don’t discount all genetic epidemiology research, understanding what genetic studies are truly measuring will be essential to translate research findings into new ways to treat and assess disease.</p><img src="https://counter.theconversation.com/content/194793/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Richard Border receives funding from the National Institutes of Health.</span></em></p><p class="fine-print"><em><span>Noah Zaitlen receives funding from the NIH, NSF, DoD, and CZI. </span></em></p>People don’t randomly select who they have children with. And that means an underlying assumption in research that tries to link particular genes to certain diseases or traits is wrong.Richard Border, Postdoctoral Researcher in Statistical Genetics, University of California, Los AngelesNoah Zaitlen, Professor of Neurology and Human Genetics, University of California, Los AngelesLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1761382022-03-31T18:17:56Z2022-03-31T18:17:56ZThe Human Genome Project pieced together only 92% of the DNA – now scientists have finally filled in the remaining 8%<figure><img src="https://images.theconversation.com/files/455098/original/file-20220329-23-6gtdap.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2070%2C1449&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Over half of the human genome contains repetitive DNA sequences whose functions are still not fully understood.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/hands-dismantling-double-helix-royalty-free-illustration/1252382129">Malte Mueller/fStop via Getty Images</a></span></figcaption></figure><p>When the <a href="https://www.genome.gov/11006929/2003-release-international-consortium-completes-hgp">Human Genome Project</a> announced that they had completed the first human genome in 2003, it was a momentous accomplishment – for the first time, the DNA blueprint of human life was unlocked. But it came with a catch – they weren’t actually able to put together all the genetic information in the genome. There were gaps: unfilled, often repetitive regions that were too confusing to piece together.</p>
<p>With advancements in technology that could handle these repetitive sequences, scientists finally <a href="https://doi.org/10.1101/2021.05.26.445798">filled those gaps in May 2021</a>, and the first end-to-end human genome was <a href="https://www.science.org/doi/10.1126/science.abj6987">officially published on Mar. 31, 2022</a>.</p>
<p>I am a <a href="https://scholar.google.com/citations?user=q3BBiy8AAAAJ&hl=en">genome biologist</a> who studies repetitive DNA sequences and how they shape genomes throughout evolutionary history. I was part of the team that helped <a href="http://www.science.org/doi/10.1126/science.abk3112">characterize the repeat sequences</a> missing from the genome. And now, with a truly complete human genome, these uncovered repetitive regions are finally being explored in full for the first time.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1415692472156495875"}"></div></p>
<h2>The missing puzzle pieces</h2>
<p>German botanist Hans Winkler coined the word “<a href="https://doi.org/10.1371/journal.pgen.1006181">genome</a>” in 1920, combining the word “gene” with the suffix “-ome,” meaning “complete set,” to describe the full DNA sequence contained within each cell. Researchers still use this word a century later to refer to the genetic material that makes up an organism. </p>
<p>One way to describe what a genome looks like is to compare it to a reference book. In this analogy, a genome is an anthology containing the DNA instructions for life. It’s composed of a vast array of nucleotides (letters) that are packaged into chromosomes (chapters). Each chromosome contains genes (paragraphs) that are regions of DNA which code for the specific proteins that allow an organism to function.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of chromosome unraveling to coiled DNA, genes and component nucleotides" src="https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=531&fit=crop&dpr=1 600w, https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=531&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=531&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=667&fit=crop&dpr=1 754w, https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=667&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/454831/original/file-20220328-15-5hb209.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=667&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Genetic material is made of DNA tightly packaged into chromosomes. Only select regions of the DNA in a genome contain genes coding for proteins.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/genes-vector-illustration-educational-royalty-free-illustration/1219077563">VectorMine/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>While every living organism has a genome, the size of that genome varies from species to species. An elephant uses the same form of genetic information as the grass it eats and the bacteria in its gut. But no two genomes look exactly alike. Some are short, like the genome of the insect-dwelling bacteria <a href="https://doi.org/10.1093/gbe/evt118"><em>Nasuia deltocephalinicola</em></a> with just 137 genes across 112,000 nucleotides. Some, like the 149 billion nucleotides of the flowering plant <a href="https://doi.org/10.1111/j.1095-8339.2010.01072.x"><em>Paris japonica</em></a>, are so long that it’s difficult to get a sense of how many genes are contained within.</p>
<p>But genes as they’ve traditionally been understood – as stretches of DNA that code for proteins – are just a small part of an organism’s genome. In fact, they make up <a href="https://dx.doi.org/10.1038%2Fnature11247">less than 2% of human DNA</a>. </p>
<p>The <a href="https://www.science.org/doi/10.1126/science.abj6987">human genome</a> contains roughly 3 billion nucleotides and just under 20,000 protein-coding genes – an estimated 1% of the genome’s total length. The remaining 99% is non-coding DNA sequences that don’t produce proteins. Some are regulatory components that work as a switchboard to control how other genes work. Others are <a href="https://doi.org/10.1155/2012/424526">pseudogenes</a>, or genomic relics that have lost their ability to function. </p>
<p>And <a href="https://doi.org/10.1101/2021.07.12.451456">over half</a> of the human genome is repetitive, with multiple copies of near-identical sequences. </p>
<h2>What is repetitive DNA?</h2>
<p>The simplest form of repetitive DNA are blocks of DNA repeated over and over in tandem called <a href="https://doi.org/10.3390/genes8090230">satellites</a>. While <a href="https://doi.org/10.1093/molbev/msq198">how much satellite DNA</a> a given genome has varies from person to person, they often cluster toward the ends of chromosomes in regions called <a href="https://doi.org/10.1016/j.febslet.2004.11.036">telomeres</a>. These regions protect chromosomes from degrading during DNA replication. They’re also found in the <a href="https://doi.org/10.3390/genes10030223">centromeres</a> of chromosomes, a region that helps keep genetic information intact when cells divide.</p>
<p>Researchers still lack a clear understanding of all the functions of satellite DNA. But because satellite DNA forms unique patterns in each person, forensic biologists and genealogists use this <a href="https://www.yourgenome.org/facts/what-is-a-dna-fingerprint">genomic “fingerprint”</a> to match crime scene samples and track ancestry. Over 50 genetic disorders are linked to variations in satellite DNA, including <a href="https://doi.org/10.1212/WNL.0b013e318249f683">Huntington’s disease</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="46 human chromosomes colored blue with white telomeres against a black screen" src="https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=638&fit=crop&dpr=1 600w, https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=638&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=638&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=802&fit=crop&dpr=1 754w, https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=802&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/455099/original/file-20220329-15-1ohcqqe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=802&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Satellite DNA tends to cluster toward the ends of chromosomes in their telomeres. Here, 46 human chromosomes are colored blue, with white telomeres.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/CRDw73">NIH Image Gallery/flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>Another abundant type of repetitive DNA are <a href="https://doi.org/10.1007/s10577-017-9569-5">transposable elements</a>, or sequences that can move around the genome.</p>
<p>Some scientists have described them as selfish DNA because they can insert themselves anywhere in the genome, regardless of the consequences. As the human genome evolved, many transposable sequences collected mutations <a href="https://doi.org/10.1186/s13100-016-0070-z">repressing</a> their ability to move to avoid harmful interruptions. But some can likely still move about. For example, transposable element insertions are linked to a number of <a href="https://doi.org/10.1186/s13100-016-0065-9">cases of hemophilia A</a>, a genetic bleeding disorder.</p>
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<figcaption><span class="caption">Transposable DNA may be the reason why humans have a tailbone but no tail.</span></figcaption>
</figure>
<p>But transposable elements aren’t just disruptive. They can have <a href="https://doi.org/10.1101/gr.218149.116">regulatory functions</a> that help control the expression of other DNA sequences. When they’re <a href="https://doi.org/10.1016/j.tig.2004.09.011">concentrated in centromeres</a>, they may also help maintain the integrity of the genes fundamental to cell survival.</p>
<p>They can also contribute to evolution. Researchers recently found that the insertion of a transposable element into a gene important to development might be why some primates, including humans, <a href="https://doi.org/10.1101/2021.09.14.460388">no longer have tails</a>. Chromosome rearrangements due to transposable elements are even linked to the genesis of new species like the <a href="https://doi.org/10.1093/molbev/msab148">gibbons of southeast Asia</a> and the <a href="https://doi.org/10.1146/annurev-animal-021419-083555">wallabies of Australia</a>.</p>
<h2>Completing the genomic puzzle</h2>
<p>Until recently, many of these complex regions could be compared to the far side of the moon: known to exist, but unseen.</p>
<p>When the <a href="https://www.genome.gov/11006929/2003-release-international-consortium-completes-hgp">Human Genome Project</a> first launched in 1990, technological limitations made it impossible to fully uncover repetitive regions in the genome. <a href="https://www.nature.com/scitable/topicpage/dna-sequencing-technologies-key-to-the-human-828/">Available sequencing technology</a> could only read about 500 nucleotides at a time, and these short fragments had to overlap one another in order to recreate the full sequence. Researchers used these overlapping segments to identify the next nucleotides in the sequence, incrementally extending the genome assembly one fragment at a time.</p>
<p>These repetitive gap regions were like putting together a 1,000-piece puzzle of an overcast sky: When every piece looks the same, how do you know where one cloud starts and another ends? With near-identical overlapping stretches in many spots, fully sequencing the genome by piecemeal became unfeasible. <a href="https://doi.org/10.1371/journal.pcbi.1003628">Millions of nucleotides</a> remained hidden in the the first iteration of the human genome.</p>
<p>Since then, sequence patches have gradually filled in gaps of the human genome bit by bit. And in 2021, the <a href="https://github.com/marbl/CHM13#telomere-to-telomere-consortium">Telomere-to-Telomere (T2T) Consortium</a>, an international consortium of scientists working to complete a human genome assembly from end to end, announced that all remaining gaps were <a href="https://www.science.org/doi/10.1126/science.abj6987">finally filled</a>. </p>
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<figcaption><span class="caption">With the completion of the first human genome, researchers are now looking toward capturing the full diversity of humanity.</span></figcaption>
</figure>
<p>This was made possible by improved sequencing technology capable of <a href="https://doi.org/10.1038/s41576-020-0236-x">reading longer sequences</a> thousands of nucleotides in length. With more information to situate repetitive sequences within a larger picture, it became easier to identify their proper place in the genome. Like simplifying a 1,000-piece puzzle to a 100-piece puzzle, long-read sequences made it <a href="http://www.science.org/doi/10.1126/science.abk3112">possible to assemble</a> large repetitive regions for the first time. </p>
<p>With the increasing power of long-read DNA sequencing technology, geneticists are positioned to explore a new era of genomics, untangling complex repetitive sequences across populations and species for the first time. And a complete, gap-free human genome provides an invaluable resource for researchers to investigate repetitive regions that shape genetic structure and variation, species evolution and human health.</p>
<p>But one complete genome doesn’t capture it all. Efforts continue to create diverse genomic references that fully represent <a href="https://humanpangenome.org">the human population</a> and <a href="https://www.earthbiogenome.org/">life on Earth</a>. With more complete, “telomere-to-telomere” genome references, scientists’ understanding of the repetitive dark matter of DNA will become more clear.</p>
<p>[<em>Get fascinating science, health and technology news.</em> <a href="https://memberservices.theconversation.com/newsletters/?nl=science&source=inline-science-fascinating">Sign up for The Conversation’s weekly science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/176138/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gabrielle Hartley receives funding from the National Science Foundation. </span></em></p>Advances in technology have enabled researchers to sequence the large regions of repetitive DNA that eluded the Human Genome Project.Gabrielle Hartley, Ph.D. Candidate in Molecular and Cell Biology, University of ConnecticutLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1617942021-07-12T15:12:42Z2021-07-12T15:12:42ZEquity and access need to be at the forefront of innovation in human genome editing<figure><img src="https://images.theconversation.com/files/409999/original/file-20210706-27-1jgbp0l.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6500%2C3656&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Genetic therapies may treat previously uncurable conditions, like sickle cell disease.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>In July 2021, after more than two years of study and consultation, the <a href="https://www.who.int/groups/expert-advisory-committee-on-developing-global-standards-for-governance-and-oversight-of-human-genome-editing">World Health Organization’s Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing</a> <a href="https://www.who.int/publications/i/item/9789240030404">released two reports</a>: a <a href="https://www.who.int/publications/i/item/9789240030060">framework for governance</a> and <a href="https://www.who.int/publications/i/item/9789240030381">recommendations</a> on human genome editing. </p>
<p>The governance framework lists a number ethical values and principles, many of which have not been included in previous international reports on human genome editing. The commitments to inclusiveness, fairness, social justice, non-discrimination, solidarity and global health justice inform the content of all three reports.</p>
<p>The committee also addressed research involving both somatic and germline human genome editing.</p>
<p>Somatic human genome editing involves making changes to the DNA of non-reproductive cells. The therapeutic aim is to correct mutations responsible for genetic disease. Germline human genome editing involves making changes to the DNA of reproductive cells. These changes become heritable when the genetically altered cells are used for reproduction. For many, heritable human genome editing is ethically contentious because of its impact on future generations.</p>
<p>As members of the WHO Expert Advisory, we appreciate the challenges in moving forward with human genome editing technology, given our commitment to ensure that this is not just personalized medicine for an elite few.</p>
<h2>Access and equity</h2>
<p>Early in the committee’s deliberations, Francis Collins, director of the National Institutes of Health in the United States, suggested that attention focused on anything other than heritable human genome editing research was a “<a href="https://www.genengnews.com/news/nih-director-backs-moratorium-for-heritable-genome-editing/">distraction</a>.” The WHO did not share this perspective, as reflected in the mandate given to the expert advisory committee. </p>
<p>For the most part, the committee elected to side-step the debate on the permissibility of heritable human genome editing and focus more broadly on issues of access and equity. On advice from the committee, WHO Director-General Tedros Adhanom Ghebreyesus stated that “<a href="https://www.who.int/news/item/26-07-2019-statement-on-governance-and-oversight-of-human-genome-editing">it would be irresponsible at this time for anyone to proceed with clinical applications of human germline genome editing</a>.”</p>
<p>To improve access to information about clinical trials involving somatic human genome editing and to promote equitable access to the potential benefits of research, in August 2019 the committee launched the <a href="https://www.who.int/groups/expert-advisory-committee-on-developing-global-standards-for-governance-and-oversight-of-human-genome-editing/registry">Human Genome Editing Registry</a>. This is a publicly accessible database currently in a pilot phase.</p>
<h2>Sickle cell disease</h2>
<p>Several potential therapies using somatic genome editing are in development, with some currently in clinical trials. </p>
<p>Sickle cell disease is an extremely painful, debilitating disease that currently can only be managed, not cured. The red blood cells of people with sickle cell disease are shaped in the form of a sickle and tend to clog up small veins, interrupting the blood flow to parts of the body and causing excruciating pain. </p>
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Read more:
<a href="https://theconversation.com/how-our-red-blood-cells-keep-evolving-to-fight-malaria-96117">How our red blood cells keep evolving to fight malaria</a>
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<p>Sickle cell disease is particularly common in areas of the world that have had a high burden of malaria — at least partly because having one gene for sickle cell disease protects against severe malaria. The <a href="https://doi.org/10.1056/NEJMra1510865">incidence of sickle cell disease is higher in tropical countries</a> and is particularly high in parts of Africa and India. Because of global migration — for instance during the transatlantic slave trade - <a href="https://doi.org/10.7189/jogh.08.021103">sickle cell disease now affects people globally</a>. </p>
<p>Because sickle cell disease is a genetic condition linked to one mutation, <a href="https://doi.org/10.1126/scitranslmed.abf2444">it lends itself well to somatic genome editing</a>. Several clinical trials are now under way (see the WHO genome editing registry for examples) and <a href="https://doi.org/10.1056/NEJMoa2031054">early results are promising</a>. The challenge, however, is that future safe and effective genome editing therapies are likely to be expensive and unlikely to be available to most people with sickle cell disease in Africa or India for many years to come.</p>
<h2>Ethical challenges</h2>
<p>The human data and materials that scientists use to develop and test new therapies comes mostly from <a href="https://doi.org/10.1038/538161a">research on men and white people</a>. A direct consequence of this is that innovative therapies are often untested or less well tested in women or people from different ethnic and racial groups. For example, <a href="https://doi.org/10.1056/NEJMsa1507092">cardiac devices were unnecessarily implanted</a> in people of African ancestry in the United States, based on genetic risk factors that predict this disease in white people. </p>
<p>Much of the scientific work leading to therapeutic innovations occurs <a href="https://healthpolicy.usc.edu/wp-content/uploads/2018/01/01.2018_Global20Burden20of20Medical20Innovation.pdf">in wealthier countries</a> with fewer resource constraints, strong health-care systems and stable infrastructure. As a consequence, <a href="https://doi.org/10.1126/science.1115538">innovations often do not accommodate the resource constraints common in poorer countries and poorer communities</a>. </p>
<p>Somatic genome editing interventions risk becoming solidly intertwined with corporate interest and profit motives. This is partly because <a href="https://doi.org/10.1038/s41587-019-0138-7">many aspects of their development have been patented</a>, increasing the cost for others wanting to use practices or materials for therapy design or delivery.</p>
<h2>Fostering innovation</h2>
<p>The WHO governance framework emphasizes ensuring that genome editing therapies are developed and made available equitably, and inclusive of global human genetic diversity. It also encourages critically analyzing the effects of proprietary ownership of genome editing technologies and future therapies. </p>
<p>As well, equitable access means fostering innovation in low- and middle-income countries. An example is the <a href="https://www.wits.ac.za/agtru/">Antiviral Gene Therapy Research Unit</a> based at the University of the Witwatersrand in South Africa. This research team investigates and seeks to develop gene therapy approaches — including genome editing — to alleviate the high burden of hepatitis B. </p>
<p>The WHO framework recommends that somatic genome editing clinical trials not be conducted in countries without effective research regulation and oversight. It also discourages trials in countries where the resultant therapies are likely to be so expensive or require such specialist care, that they are unlikely ever to be made available. Specifically, this means that clinical trials for somatic genome editing innovations should only be conducted in countries where it’s likely that the innovation would be marketed, and where there is robust ethics oversight. </p>
<p>Somatic human genome editing research offers previously unimaginable pathways to alleviating suffering for millions of people living with conditions such as sickle cell disease. Unless specific attention is paid to ensuring the development of affordable innovations that can be implemented across the globe, these benefits may never reach the global poor.</p><img src="https://counter.theconversation.com/content/161794/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jantina De Vries is a member of the WHO Expert Advisory Committee on Developing Global Standards for Governance.</span></em></p><p class="fine-print"><em><span>Françoise Baylis a member of the WHO Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing, a member of a Working Group to inform the development of the WHO Global Guidance Framework to Harness the Responsible Use of the Life Sciences, May to July 2021, and a member of Planning Committee for the Third International Summit on Human Genome Editing’, London, 7-9 March 2022. </span></em></p>Scientists have been eager to edit genomes to eliminate certain diseases. New WHO reports outlines ethical approaches to research and treatment.Jantina de Vries, Associate professor, Medicine, University of Cape TownFrançoise Baylis, Research Professor, Philosophy, Dalhousie UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1624182021-06-09T07:32:59Z2021-06-09T07:32:59ZWhy it took 20 years to ‘finish’ the human genome — and why there’s still more to do<figure><img src="https://images.theconversation.com/files/405260/original/file-20210609-27-1n86l2m.png?ixlib=rb-1.1.0&rect=0%2C2%2C752%2C357&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Human_genome.png">Webridge/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>The release of the <a href="https://www.nature.com/articles/35057062">draft human genome sequence</a> in 2001 was a seismic moment in our understanding of the human genome, and paved the way for advances in our understanding of the genomic basis of human biology and disease.</p>
<p>But sections were left unsequenced, and some sequence information was incorrect. Now, two decades later, we have a much more complete version, <a href="https://www.biorxiv.org/content/10.1101/2021.05.26.445798v1">published as a preprint</a> (which is yet to undergo peer review) by an international consortium of researchers.</p>
<p>Technological limitations meant the original draft human genome sequence covered just the “euchromatic” portion of the genome — the 92% of our genome where most genes are found, and which is most active in making gene products such as RNA and proteins. </p>
<p>The newly updated sequence fills in most of the remaining gaps, providing the full 3.055 billion base pairs (“letters”) of our DNA code in its entirety. This data has been made publicly available, in the hope other researchers will use it to further their research.</p>
<h2>Why did it take 20 years?</h2>
<p>Much of the newly sequenced material is the “heterochromatic” part of the genome, which is more “tightly packed” than the euchromatic genome and contains many highly repetitive sequences that are very challenging to read accurately.</p>
<p>These regions were once thought not to contain any important genetic information but they are now known to contain genes that are involved in fundamentally important processes such as the formation of organs during embryonic development. Among the 200 million newly sequenced base pairs are an estimated 115 genes predicted to be involved in producing proteins. </p>
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<a href="https://theconversation.com/explainer-what-is-the-human-genome-project-7559">Explainer: what is the Human Genome Project?</a>
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<p>Two key factors made the completion of the human genome possible:</p>
<p><strong>1. Choosing a very special cell type</strong></p>
<p>The newly published genome sequence was created using human cells derived from a very rare type of tissue called a complete <a href="https://www.thewomens.org.au/health-information/pregnancy-and-birth/pregnancy-problems/early-pregnancy-problems/hydatidiform-mole">hydatidiform mole</a>, which occurs when a fertilised egg loses all the genetic material contributed to it by the mother.</p>
<p>Most cells contain two copies of each chromosome, one from each parent and each parent’s chromosome contributing a different DNA sequence. A cell from a complete hydatidiform mole has two copies of the father’s chromosomes only, and the genetic sequence of each pair of chromosomes is identical. This makes the full genome sequence much easier to piece together.</p>
<p><strong>2. Advances in sequencing technology</strong></p>
<p>After decades of glacial progress, the Human Genome Project achieved its 2001 breakthrough by pioneering a method called “shotgun sequencing”, which involved breaking the genome into very small fragments of about 200 base pairs, <a href="https://www.genome.gov/genetics-glossary/Bacterial-Artificial-Chromosome">cloning them inside bacteria</a>, deciphering their sequences, and then piecing them back together like a giant jigsaw.</p>
<p>This was the main reason the original draft covered only the euchromatic regions of the genome — only these regions could be reliably sequenced using this method.</p>
<p>The latest sequence was deduced using two complementary new DNA-sequencing technologies. One was developed by PacBio, and allows longer DNA fragments to be sequenced with very high accuracy. The second, developed by Oxford Nanopore, produces ultra-long stretches of continuous DNA sequence. These new technologies allows the jigsaw pieces to be thousands or even millions of base pairs long, making it easier to assemble.</p>
<p>The new information has the potential to advance our understanding of human biology including how chromosomes function and maintain their structure. It is also going to improve our understanding of genetic conditions such as Down syndrome that have an underlying chromosomal abnormality.</p>
<h2>Is the genome now completely sequenced?</h2>
<p>Well, no. An obvious omission is the Y chromosome, because the complete hydatidiform mole cells used to compile this sequence contained two identical copies of the X chromosome. However, this work is underway and the researchers anticipate their method can also accurately sequence the Y chromosome, despite it having highly repetitive sequences.</p>
<p>Even though sequencing the (almost) complete genome of a human cell is an extremely impressive landmark, it is just one of several crucial steps towards fully understanding humans’ genetic diversity.</p>
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Read more:
<a href="https://theconversation.com/how-much-junk-is-in-our-dna-53929">How much ‘junk’ is in our DNA?</a>
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<p>The next job will be to study the genomes of diverse populations (the complete hydatidiform mole cells were European). Once the new technology has matured sufficiently to be used routinely to sequence many different human genomes, from different populations, it will be better positioned to make a more significant impact on our understanding of human history, biology and health. </p>
<p>Both care and technological development are needed to ensure this research is conducted with a full understanding of the diversity of the human genome to prevent exacerbation of health disparities by limiting discoveries to specific populations.</p><img src="https://counter.theconversation.com/content/162418/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Melissa Southey receives funding from the NHMRC, NBCF, PCFA, NIH (USA), VCA, CCV, DJPR (VIC) and Monash University. She is affiliated with Cancer Council Victoria and The University of Melbourne. </span></em></p><p class="fine-print"><em><span>Tu Nguyen-Dumont is a recipient of a Fellowship from the National Breast Cancer Foundation (ECF-17-001).</span></em></p>Two decades after the ‘full’ human genetic code was released to global fanfare, researchers have finally filled in the blanks that made up 8% of the sequence, thanks to recent advances in genome sequencing.Melissa Southey, Chair Precision Medicine, Monash UniversityTu Nguyen-Dumont, Senior research fellow, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1572102021-04-15T12:39:17Z2021-04-15T12:39:17ZScientists are on a path to sequencing 1 million human genomes and use big data to unlock genetic secrets<figure><img src="https://images.theconversation.com/files/395117/original/file-20210414-20-1od1b13.png?ixlib=rb-1.1.0&rect=32%2C64%2C3047%2C2349&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A complete human genome, seen here in pairs of chromosomes, offers a wealth of information, but it is hard connect genetics to traits or disease.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:UCSC_human_chromosome_colours.png#/media/File:UCSC_human_chromosome_colours.png">HYanWong/Wikimedia Comons</a></span></figcaption></figure><p>The first draft of the human genome was <a href="https://www.washingtonpost.com/archive/politics/2000/06/27/teams-finish-mapping-human-dna/3af9bfcf-e7b6-4ac1-bcdb-f4fc117c19bd/">published 20 years ago</a> in <a href="https://www.genome.gov/25520483/online-education-kit-2001-first-draft-of-the-human-genome-sequence-released">2001</a>, took nearly three years and cost <a href="https://www.genome.gov/about-genomics/fact-sheets/Sequencing-Human-Genome-cost">between US$500 million and $1 billion</a>. The <a href="https://www.genome.gov/human-genome-project">Human Genome Project</a> has allowed scientists to read, almost end to end, the 3 billion pairs of DNA bases – or “letters” – that biologically define a human being. </p>
<p>That project has allowed a new generation of <a href="https://scholar.google.com/citations?user=Yy8gde8AAAAJ&hl=en&oi=ao">researchers like me</a>, currently a postdoctoral fellow at the National Cancer Institute, to identify <a href="https://doi.org/10.1038/s41586-020-2099-x">novel targets for cancer treatments</a>, engineer <a href="https://doi.org/10.1038/s41590-019-0416-z">mice with human immune systems</a> and even build a <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr14%3A95086244%2D95158010&hgsid=1066518897_QJL7hsBNGEhTnw6DgqcZaMG4YFB2">webpage where anyone can navigate the entire human genome</a> with the same ease with which you use Google Maps.</p>
<p>The first complete genome was generated from a handful of anonymous donors to try to produce a reference genome that represented more than just one single individual. But this fell far short of encompassing <a href="https://doi.org/10.1038/nature18964">the wide diversity of human populations in the world</a>. No two people are the same and no two genomes are the same, either. If researchers wanted to understand humanity in all its diversity, it would take sequencing thousands or millions of complete genomes. Now, a project like that is underway. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A diverse group of people." src="https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=493&fit=crop&dpr=1 600w, https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=493&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=493&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=619&fit=crop&dpr=1 754w, https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=619&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=619&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">There is a huge amount of genetic variation between people around the globe.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/group-portrait-of-people-smiling-royalty-free-image/560447233?adppopup=true">Flashpop/DigitalVision via Getty Images</a></span>
</figcaption>
</figure>
<h2>Understanding genetic diversity</h2>
<p>The wealth of genetic variation among people is what makes each person unique. But genetic changes also cause many disorders and make some groups of people more susceptible to certain diseases than others.</p>
<p>Around the time of the Human Genome Project, researchers were also sequencing the complete genomes of organisms such as <a href="https://doi.org/10.1038/nature01262">mice</a>, <a href="https://doi.org/10.1126/science.287.5461.2185">fruit flies</a>, <a href="https://doi.org/10.1126/science.274.5287.546">yeasts</a> and <a href="https://doi.org/10.1038/35048692">some plants</a>. The huge effort made to generate these first genomes led to a revolution in the technology required to read genomes. Thanks to these advances, instead of taking years and costing hundreds of millions of dollars to sequence a whole human genome, it now takes <a href="https://www.genome.gov/about-genomics/fact-sheets/Sequencing-Human-Genome-cost">a few days and costs merely a thousand dollars</a>. Genome sequencing is very different from genotyping services like 23 and Me or Ancestry, which look at only a tiny fraction of locations in a person’s genome.</p>
<p>Advances in technology have allowed scientists to sequence the complete genomes of thousands of individuals from around the world. Initiatives such as the <a href="https://gnomad.broadinstitute.org/">Genome Aggregation Consortia</a> are currently making efforts to collect and organize this scattered data. So far, that group has been able to gather nearly <a href="https://doi.org/10.1038/s41586-020-03174-8">150,000 genomes</a> that show an incredible amount of human genetic diversity. Within that set, researchers have found more than 241 million differences in people’s genomes, <a href="https://doi.org/10.1038/nature19057">with an average of one variant for every eight base pairs</a>.</p>
<p>Most of these variations are very rare and will have no effect on a person. However, hidden among them are variants with important physiological and medical consequences. For example, certain variants in the BRCA1 gene predispose some groups of woman, like Ashkenazi Jews, to <a href="https://doi.org/10.1038/s41586-018-0461-z">ovarian and breast cancer</a>. Other variants in that gene lead some <a href="https://doi.org/10.1038/s41467-018-06616-0">Nigerian women to experience higher-than-normal mortality</a> from breast cancer. </p>
<p>The best way researchers can identify these types of population-level variants is through <a href="https://www.ebi.ac.uk/gwas/">genomewide association studies</a> that compare the genomes of large groups of people with a control group. But diseases are complicated. An individual’s lifestyle, symptoms and time of onset can vary greatly, and the effect of genetics on many diseases is hard to distinguish. The predictive power of current genomic research is too low to tease out many of these effects because <a href="https://doi.org/10.1038/s41588-018-0313-7">there isn’t enough genomic data</a>.</p>
<p>Understanding the genetics of complex diseases, especially those related to the genetic differences among ethnic groups, is essentially a big data problem. And researchers need more data.</p>
<h2>1,000,000 genomes</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="The double helix DNA structure." src="https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1038&fit=crop&dpr=1 600w, https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1038&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1038&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1304&fit=crop&dpr=1 754w, https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1304&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1304&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The link between genetics and disease is nuanced, but the more genomes you can study, the easier it is to find those links.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:DNA_animation.gif#/media/File:DNA_animation.gif">brian0918/Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>To address the need for more data, the National Institutes of Health has started a program called <a href="https://allofus.nih.gov/">All of Us</a>. The project aims to collect genetic information, medical records and health habits from surveys and wearables of more than a million people in the U.S. over the course of 10 years. It also has a goal of gathering more data from underrepresented minority groups to facilitate the study of health disparities. The <a href="https://www.fda.gov/regulatory-information/selected-amendments-fdc-act/21st-century-cures-act">All of Us project</a> opened to public enrollment in 2018, and more than 270,000 people have contributed samples since. The project is continuing to recruit participants from all 50 states. Participating in this effort are many academic laboratories and private companies.</p>
<p>This effort could benefit scientists from a wide range of fields. For instance, a neuroscientist could look for genetic variations associated with depression while taking into account exercise levels. An oncologist could search for variants that correlate with reduced risk of skin cancer while exploring the influence of ethnic background.</p>
<p>A million genomes and the accompanying health and lifestyle information will provide an extraordinary wealth of data that should allow researchers to discover the effects of genetic variation on diseases, not only for individuals, but also within different groups of people.</p>
<p>[<em>Understand new developments in science, health and technology, each week.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p>
<h2>The dark matter of the human genome</h2>
<p>Another benefit of this project is that it will allow scientists to learn about parts of the human genome that are currently very hard to study. Most genetic research has been on the parts of the genome that encode for proteins. However, these represent only <a href="https://dx.doi.org/10.1038%2Fnrd.2018.93">1.5% of the human genome</a>.</p>
<p>My research focuses on RNA – a molecule that turns the messages encoded in a person’s DNA into proteins. However, RNAs that come from the 98.5% of the human genome that doesn’t make proteins have a myriad of functions by themselves. Some of these noncoding RNAs are involved in processes such as <a href="https://doi.org/10.1038/nature08975">how cancer spreads</a>, <a href="https://doi.org/10.1242/dev.146613">embryonic development</a> or <a href="https://doi.org/10.1038/35047580">controlling the X chromosome in females</a>. In particular, I study how genetic variations can influence the intricate folding that allows noncoding RNAs to do their jobs. Since the All of Us project includes all coding and noncoding parts of the genome, it is going to be by far the largest dataset relevant to my work and will hopefully shed light on these mysterious RNAs.</p>
<p>The first human genome sparked 20 years of incredible scientific progress. I think it is almost certain that a huge dataset of genomic variations will unlock clues about complex diseases. Thanks to large-scale population studies and big-data projects such as All of Us, researchers are paving the way to answering, in the next decade, how our individual genetics shape our health.</p>
<p><em>A photo in this story was updated to better represent our editorial guidelines.</em></p><img src="https://counter.theconversation.com/content/157210/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Xavier Bofill De Ros receives funding from the National Institutes of Health (NIH). He is affiliated with ECUSA, an association of Spanish scientists in the USA.</span></em></p>The first full human genome was sequenced 20 years ago. Now, a project is underway to sequence 1 million genomes to better understand the complex relationship between genetics, diversity and disease.Xavier Bofill De Ros, Research Fellow in RNA biology, National Institutes of HealthLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1553492021-02-19T18:22:46Z2021-02-19T18:22:46ZThe human genome at 20: how biology’s most-hyped breakthrough led to anticlimax and arrests<figure><img src="https://images.theconversation.com/files/385281/original/file-20210219-21-rkb5rg.jpg?ixlib=rb-1.1.0&rect=40%2C0%2C8946%2C5982&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-illustration-virus-dna-molecule-structure-1371386951">Rost9/Shutterstock</a></span></figcaption></figure><p>When President Bill Clinton took to a White House lectern 20 years ago to announce that the <a href="https://home.bt.com/news/on-this-day/june-26-2000-the-book-of-life-falls-open-as-scientists-crack-the-human-genome-11363988716324">human genome sequence</a> had been completed, he hailed the breakthrough as “the most important, most wondrous map ever produced by humankind”. The scientific achievement was placed on par with the moon landings.</p>
<p>It was hoped that having access to the sequence would transform our understanding of human disease <a href="https://web.ornl.gov/sci/techresources/Human_Genome/project/clinton3.shtml">within 20 years</a>, leading to better treatment, detection and prevention. The famous <a href="https://science.sciencemag.org/content/291/5507/1304.full">journal article</a> that shared our genetic ingredients with the world, published in February 2001, was welcomed as a “Book of Life” that could revolutionise medicine by showing which of our genes led to which illnesses.</p>
<p>But in the two decades since, the sequence has underwhelmed. The potential of our newfound genetic self-knowledge has not been fulfilled. Instead, what has emerged is a new frontier in genetic research: new questions for a new batch of researchers to answer. </p>
<p>Today, the gaps between our genes, and the switches that direct genetic activity, are emerging as powerful determinants behind how we look and how we get ill – perhaps deciding <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877666/">up to 90%</a> of what makes us different from one another. Understanding this “<a href="https://theconversation.com/discovering-how-genetic-dark-matter-plays-a-role-in-mental-illness-is-just-the-tip-of-the-iceberg-for-human-health-142326">genetic dark matter</a>”, using the knowledge provided by the human genome sequence, will help us to push further into our species’ genetic secrets.</p>
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<figcaption><span class="caption">The announcement was first made in a joint press conference between President Bill Clinton and Prime Minister Tony Blair in 2000.</span></figcaption>
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<h2>Unravelled code</h2>
<p>Cracking the human genetic code took 13 years, US$2.7 billion (£1.9 billion) and hundreds of scientists peering through over 3 billion base pairs in our DNA. Once mapped, our genetic data helped projects like the <a href="https://depmap.sanger.ac.uk/">Cancer Dependency Map</a> and the <a href="https://www.genome.gov/about-genomics/fact-sheets/Genome-Wide-Association-Studies-Fact-Sheet">Genome Wide Association Studies</a> better understand the diseases that afflict humans.</p>
<p>But some results were disappointing. Back in 2000, as it was becoming clear the genome sequence was imminent, the genomics community began excitedly placing bets predicting how many genes the human genome would contain. Some bets were as high as 300,000, others as low as 40,000. For context, the onion genome contains 60,000 genes.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-a-gene-12951">Explainer: what is a gene?</a>
</strong>
</em>
</p>
<hr>
<p>Dispiritingly, it turned out that our genome contains roughly the same number of genes as a mouse or a fruit fly (around 21,000), and three times less than <a href="https://www.sciencedirect.com/science/article/abs/pii/S2352407316300166">an onion</a>. Few would argue that humans are three times less complex than an onion. Instead, this discovery suggested that the number of genes in our genome had little to do with our complexity or our difference from other species, as had been previously assumed.</p>
<h2>Great responsibility</h2>
<p>Access to the human genome sequence also presented the scientific community with a huge number of important <a href="https://pubmed.ncbi.nlm.nih.gov/1825074/">ethical questions</a>,
underscored in 2000 by Prime Minister Tony Blair when he cautioned: “With the power of this discovery comes the responsibility to use it wisely.”</p>
<p>Ethicists were particularly concerned about questions of “genetic discrimination”, like whether our genes could be used against us as evidence in a court of law, or as a basis for exclusion: a new kind of twisted hierarchy determined by our biology.</p>
<p>Some of these concerns were addressed by legislation against <a href="https://www.genome.gov/about-genomics/policy-issues/Genetic-Discrimination">genetic discrimination</a>, like the US Genetic Information Nondiscrimination Act of 2008. Other concerns, like those around so-called “designer babies”, are still being put to the test today.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/should-we-edit-the-genomes-of-human-embryos-a-geneticist-and-social-scientist-discuss-100355">Should we edit the genomes of human embryos? A geneticist and social scientist discuss</a>
</strong>
</em>
</p>
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<p>In 2018, human embryos were gene edited by a Chinese scientist, using a method called CRISPR which allows targeted sections of DNA to be snipped off and replaced with others. The scientist involved was subsequently <a href="https://www.nature.com/articles/d41586-020-00001-y">jailed</a>, suggesting that there remains little appetite for <a href="https://www.who.int/ethics/topics/human-genome-editing/WHO-Commissioned-Ethics-paper-March19.pdf">human genetic experimentation</a>. </p>
<p>On the other hand, to <a href="https://www.nature.com/articles/d41586-019-01906-z">deny available genetic treatments</a> to willing patients may one day be considered unethical – just as some countries have chosen to legalise euthanasia on ethical grounds. Questions remain about how humanity should handle its genetic data.</p>
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<figcaption><span class="caption">The Chinese scientist He Jiankui announced in 2018 that he had created gene-edited twins. He was jailed in 2019.</span></figcaption>
</figure>
<h2>Disease diversions</h2>
<p>With human gene editing still highly contentious, researchers have instead looked to find out which genes may be responsible for humanity’s illnesses. Yet when scientists <a href="https://www.genome.gov/about-genomics/fact-sheets/Genome-Wide-Association-Studies-Fact-Sheet">investigated which genes</a> are linked to human diseases, they were met with a surprise. After comparing huge samples of human DNA to find whether certain genes led to certain illnesses, they found that many unexpected sections of the genome were involved in the development of human disease.</p>
<p>The genome contains two sections: the coding genome, and the non-coding genome. The coding genome represents just 1.7% of our DNA, but is responsible for coding the proteins that are the essential building blocks of life. Genes are defined by their ability to code proteins: so 1.7% of our genome consists of genes. </p>
<p>The non-coding genome, which makes up the remaining 98.3% of our DNA, doesn’t code proteins. This largely unknown section of the genome was once dismissed as “junk DNA”, previously thought to be useless. It contained no protein-creating genes, so it was assumed the non-coding genome had little to do with the stuff of life.</p>
<p>Bewilderingly, scientists found that the <a href="https://science.sciencemag.org/content/306/5696/636.abstract">non-coding genome</a> was actually responsible for the majority of information that <a href="https://pubmed.ncbi.nlm.nih.gov/28622505/">impacted disease development</a> in humans. Such findings have made it clear that the non-coding genome is actually far more important than previously thought.</p>
<h2>Enhanced capabilities</h2>
<p>Within this non-coding part of the genome, researchers have subsequently found short regions of DNA called enhancers: gene switches that turn genes on and off in different tissues at different times. They found that enhancers needed to shape the embryo have changed very <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561167/">little during evolution</a>, suggesting that they represent a major and important source of genetic information.</p>
<p>These studies inspired one of us, Alasdair, to explore the possible role of enhancers in behaviours such as alcohol intake, anxiety and fat intake. By comparing the genomes of mice, birds and humans we identified an enhancer that has changed relatively little over 350 million years – suggesting its importance in species’ survival. </p>
<p>When we used CRISPR genome editing to delete this enhancer from the mouse genome, those mice <a href="https://pubmed.ncbi.nlm.nih.gov/31445429/">ate less fat</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/32203157/">drank less alcohol</a>, and displayed reduced anxiety. While these may all sound like positive changes, it’s likely that these enhancers evolved in calorifically poor environments full of predators and threats. At the time, eating high-calorie food sources such as fat and fermented fruit, and being hyper-vigilant of predators, would have been key for survival. However, in modern society these same behaviours may now contribute to obesity, alcohol abuse and chronic anxiety.</p>
<p>Intriguingly, subsequent genetic analysis of a <a href="https://www.ukbiobank.ac.uk/">major human population cohort</a> has shown that changes in the same human enhancer were also associated with <a href="https://pubmed.ncbi.nlm.nih.gov/32203157/">differences in alcohol intake and mood</a>. These studies demonstrate that enhancers are not only important for normal physiology and health, but that changing them could result in changes in behaviour that have major implications for human health.</p>
<p>Given these new avenues of research, we appear to be at a crossroads in genetic biology. The importance of gene enhancers in health and disease sits uncomfortably with our relative inability to identify and understand them. </p>
<p>And so in order to make the most of the sequencing of the human genome two decades ago, it’s clear that research must now look beyond the 1.7% of the genome that encodes proteins. In exploring uncharted genetic territory, like that represented by enhancers, biology may well locate the next swathe of healthcare breakthroughs.</p>
<p><em>This article was updated on February 21, 2021 to clarify that DNA base pairs are not made from proteins.</em></p><img src="https://counter.theconversation.com/content/155349/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alasdair Mackenzie receives funding from the BBSRC, Tenovus (Scotland) and Medical Research Scotland</span></em></p><p class="fine-print"><em><span>Andreas Kolb does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The achievement didn’t live up to the hype, but it has illuminated new areas of ‘genetic dark matter’.Alasdair Mackenzie, Reader, Molecular Genetics, University of AberdeenAndreas Kolb, Senior Research Fellow, The Rowett Institute, University of AberdeenLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1473482020-10-02T05:59:19Z2020-10-02T05:59:19ZWe discovered a missing gene fragment that’s shedding new light on how males develop<figure><img src="https://images.theconversation.com/files/361307/original/file-20201002-14-1d9hcq7.jpg?ixlib=rb-1.1.0&rect=61%2C88%2C5827%2C1677&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>It’s one of the most important genes in biology: “Sry”, the gene that makes males male. Development of the sexes is a crucial step in sexual reproduction and is essential for the survival of almost all animal species.</p>
<p>Today in the journal <a href="https://science.sciencemag.org/content/370/6512/121">Science</a>, my international collaborators and I report the surprise discovery of an entirely new part of the Sry gene in mice — a part we had no idea existed.</p>
<p>I co-discovered Sry <a href="https://pubmed.ncbi.nlm.nih.gov/2374589/">in 1990</a>. It is the gene on the Y (male) chromosome that leads to the development of male characteristics in mice, humans and most other mammals. Since then, Sry has been the subject of intense study worldwide because of its fundamental role in mammalian biology. </p>
<p>We have come to understand, in some detail, how Sry acts to trigger a cascade of gene activity that results in the formation of testes, instead of ovaries, in the embryo. Testes then stimulate the formation of other male characteristics.</p>
<p>But it’s clear we don’t have all the answers just yet. Our results published today take us one step further in the right direction.</p>
<h2>Hidden in plain sight</h2>
<p>For 30 years, we have understood the Sry gene is made up of one “exon”, a segment of a gene used to code for amino acids, the building blocks of proteins. This can be compared to a computer file consisting of one contiguous block of data, on a hard disk.</p>
<p>Our newest research reveals there’s actually a second exon in mouse Sry. This is like finding a whole new separate block of previously hidden data. </p>
<p>The mouse genome, like the human genome, has been extensively characterised due to the availability of advanced <a href="https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Fact-Sheet">DNA sequencing</a> and related technologies. Researchers <a href="https://pubmed.ncbi.nlm.nih.gov/30124169/">commonly assume</a> all the genes and all the parts of the genes have already been discovered.</p>
<p>But earlier this year, scientists in Japan uncovered what looked like a new piece of the Sry gene in mice. New sequencing approaches revealed what appeared to be two versions of Sry: a short, single-exon form and a longer, two-exon form. They called this two-exon version “Sry-T”. </p>
<p>They collaborated with my group at the University of Queensland and removed the new exon using <a href="https://www.sciencealert.com/crispr-gene-editing">CRISPR</a>, a gene editing tool that lets researchers alter DNA precisely. Together we discovered this prevented Sry from functioning: XY mice (which would normally develop as males) developed as females instead. </p>
<p>Conversely, adding Sry-T to fertilised XX mouse eggs (which would normally develop as females) resulted in males. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/361300/original/file-20201002-20-bnwrzk.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Two mice hang from a wooden bar." src="https://images.theconversation.com/files/361300/original/file-20201002-20-bnwrzk.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/361300/original/file-20201002-20-bnwrzk.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=465&fit=crop&dpr=1 600w, https://images.theconversation.com/files/361300/original/file-20201002-20-bnwrzk.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=465&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/361300/original/file-20201002-20-bnwrzk.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=465&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/361300/original/file-20201002-20-bnwrzk.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=585&fit=crop&dpr=1 754w, https://images.theconversation.com/files/361300/original/file-20201002-20-bnwrzk.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=585&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/361300/original/file-20201002-20-bnwrzk.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=585&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">On the left, an XY mouse lacking Sry-T that developed as female. On the right, an XX mouse carrying the Sry-T gene that developed as male.</span>
<span class="attribution"><span class="source">Makoto Tachibana, Osaka University</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<h2>Implications for human sex determination</h2>
<p>Importantly, although human Sry does not have the added exon, our discovery may reveal new functions that might be shared between mouse and human Sry. </p>
<p>The DNA sequence of the new exon in Sry-T may point us towards discovering some of the genes and proteins that interact with Sry, something that has been elusive up till now. </p>
<p>And interactions we find in mice may also occur in humans. Studying what human Sry interacts with may help explain some cases of differences in human sex development, otherwise known as <a href="http://www.dsdgenetics.org/index.php">“intersex” development</a>. This is a common but poorly understood group of <em>mostly</em> genetic conditions that arise in humans. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/361320/original/file-20201002-21-f70nsk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Symbols used to indicate 'male', 'female' and 'intersex'." src="https://images.theconversation.com/files/361320/original/file-20201002-21-f70nsk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/361320/original/file-20201002-21-f70nsk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/361320/original/file-20201002-21-f70nsk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/361320/original/file-20201002-21-f70nsk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/361320/original/file-20201002-21-f70nsk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/361320/original/file-20201002-21-f70nsk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/361320/original/file-20201002-21-f70nsk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Intersex refers to people who are born with genetic, hormonal or physical sex characteristics that are not typically ‘male’ or ‘female’.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Currently, we don’t know the genetics behind a large proportion of intersex conditions. This is partly because we don’t yet know all the genes involved in the human sex development pathway.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/sex-genes-the-y-chromosome-and-the-future-of-men-32893">Sex, genes, the Y chromosome and the future of men</a>
</strong>
</em>
</p>
<hr>
<h2>Towards a better understanding of male sex development</h2>
<p>Scientifically, this discovery is a bit like discovering a new cell type in the body, or a new asteroid in the Kuiper belt. As with many scientific discoveries, it challenges what we thought we knew and raises many questions. </p>
<p>What is the function of the new exon in Sry-T? </p>
<p>Currently, we only have part of the answer. It turns out the first exon of Sry, the one we already knew about, contains “instability sequences” at its end. These are sequences that cause proteins to fray and degrade. </p>
<p>An important function of the newly discovered second exon is to mask the instability sequences, seal the end of the Sry protein and prevent it from degrading. In other words, this second exon is crucial to the development of male babies. </p>
<p>What’s more, this protection mechanism represents an unusual and intriguing evolutionary mechanism that has acted to help stop vulnerable Y-chromosome genes from literally falling apart.</p>
<p>But it’s early days yet. The challenge now is to understand whether there are more functions hidden within the newly discovered exon. </p>
<p>If so, this information may provide some of the missing links that have stood in the way of our full understanding of how Sry works at a molecular level and of how males and females come to be.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-education-about-gender-and-sexuality-does-belong-in-the-classroom-102902">Why education about gender and sexuality does belong in the classroom</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/147348/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Koopman is Emeritus Professor of Developmental Biology at the University of Queensland. He has previously received funding from the Australian Research Council and the National Health and Medical Research Council of Australia.</span></em></p>A new finding in mice rewrites the textbook explanation of the male sex-determining gene, Sry. It might also help us better understand how males and females come to be.Peter Koopman, Professorial Research Fellow, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1305682020-02-11T13:53:48Z2020-02-11T13:53:48ZWhy sequencing the human genome failed to produce big breakthroughs in disease<figure><img src="https://images.theconversation.com/files/314042/original/file-20200206-43089-1b0x437.jpg?ixlib=rb-1.1.0&rect=17%2C8%2C5973%2C3440&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Early proponents of genome sequencing made misleading predictions about its potential in medicine.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/innovative-science-medicine-concept-design-576826981">Natali_ Mis/Shutterstock.com</a></span></figcaption></figure><p>An emergency room physician, initially unable to diagnose a disoriented patient, finds on the patient a wallet-sized card providing access to his genome, or all his DNA. The physician quickly searches the genome, diagnoses the problem and sends the patient off for a gene-therapy cure. That’s what a Pulitzer prize-winning <a href="https://www.latimes.com/archives/la-xpm-1996-03-03-tm-42636-story.htm">journalist imagined</a> 2020 would look like when she reported on the Human Genome Project back in 1996.</p>
<h2>A new era in medicine?</h2>
<p>The Human Genome Project was an international scientific collaboration that successfully mapped, sequenced and made publicly available the genetic content of human chromosomes – or all human DNA. Taking place between 1990 and 2003, the project caused many to speculate about the future of medicine. In 1996, Walter Gilbert, a Nobel laureate, <a href="https://www.latimes.com/archives/la-xpm-1996-03-03-tm-42636-story.html">said</a>, “The results of the Human Genome Project will produce a tremendous shift in the way we can do medicine and attack problems of human disease.” In 2000, Francis Collins, then head of the HGP at the National Institutes of Health, <a href="https://web.ornl.gov/sci/techresources/Human_Genome/project/clinton3.shtml">predicted</a>, “Perhaps in another 15 or 20 years, you will see a complete transformation in therapeutic medicine.” The same year, President Bill Clinton <a href="https://www.cnn.com/2000/HEALTH/06/26/human.genome.05/index.html">stated</a> the Human Genome Project would “revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.”</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/314040/original/file-20200206-43113-hf9gqo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/314040/original/file-20200206-43113-hf9gqo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/314040/original/file-20200206-43113-hf9gqo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=389&fit=crop&dpr=1 600w, https://images.theconversation.com/files/314040/original/file-20200206-43113-hf9gqo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=389&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/314040/original/file-20200206-43113-hf9gqo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=389&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/314040/original/file-20200206-43113-hf9gqo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=488&fit=crop&dpr=1 754w, https://images.theconversation.com/files/314040/original/file-20200206-43113-hf9gqo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=488&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/314040/original/file-20200206-43113-hf9gqo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=488&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">President Clinton, flanked by J. Craig Venter, left, and Francis Collins, right, announces the completion of a rough draft of the human genome on June 26, 2000.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Associated-Press-Domestic-News-Dist-of-Columbi-/570adf5762e5da11af9f0014c2589dfb/17/0">AP Photo/Rick Bowmer</a></span>
</figcaption>
</figure>
<p>It is now 2020 and no one carries a genome card. Physicians typically do not examine your DNA to diagnose or treat you. Why not? As I explain in a recent <a href="https://doi.org/10.1080/01677063.2019.1706093">article in the Journal of Neurogenetics</a>, the causes of common debilitating diseases are complex, so they typically are not amenable to simple genetic treatments, despite the hope and hype to the contrary.</p>
<h2>Causation is complex</h2>
<p>The idea that a single gene can cause common diseases has been around for several decades. In the late 1980s and early 1990s, high-profile scientific journals, including Nature and JAMA, announced single-gene causation of <a href="https://doi.org/10.1038/325783a0">bipolar disorder</a>, <a href="https://doi.org/10.1038/336164a0">schizophrenia</a> and <a href="https://doi.org/10.1001/jama.1990.03440150063027">alcoholism</a>, among other conditions and behaviors. These articles drew <a href="https://www.washingtonpost.com/archive/politics/1987/02/26/manic-depression-gene-found/16b6f549-127c-44ed-8b75-75fcf52f60b9/">massive attention</a> in the <a href="https://www.nytimes.com/1990/04/18/us/scientists-see-a-link-between-alcoholism-and-a-specific-gene.html">popular media</a>, but were <a href="https://doi.org/10.1038/342238a0">soon</a> <a href="https://doi.org/10.1038/ng0193-49">retracted</a> <a href="https://doi.org/10.1038/325806a0">or</a> <a href="https://doi.org/10.1038/336167a0">failed</a> <a href="https://doi.org/10.1001/jama.1991.03470130081033">attempts</a> <a href="https://doi.org/10.1001/jama.1993.03500130087038">at</a> <a href="https://doi.org/10.1002/ajmg.1320540202">replication</a>. These reevaluations completely undermined the initial conclusions, which often had relied on <a href="https://doi.org/10.1016/0166-2236(93)90003-5">misguided statistical tests</a>. Biologists were generally aware of these developments, though the follow-up studies received little attention in popular media.</p>
<p>There are indeed individual gene mutations that cause devastating disorders, such as <a href="https://doi.org/10.1038/306234a0">Huntington’s disease</a>. But most common debilitating diseases are not caused by a mutation of a single gene. This is because people who have a debilitating genetic disease, on average, do not survive long enough to have numerous healthy children. In other words, there is strong evolutionary pressure against such mutations. Huntington’s disease is an exception that endures because it typically does not produce symptoms until a patient is beyond their reproductive years. Although new mutations for many other disabling conditions occur by chance, they don’t become frequent in the population. </p>
<p>Instead, most common debilitating diseases are caused by combinations of mutations in many genes, each having a very small effect. They interact with one another and with environmental factors, modifying the production of proteins from genes. The many kinds of microbes that live within the human body can play a role, too. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/314055/original/file-20200206-43079-1u32hbe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/314055/original/file-20200206-43079-1u32hbe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/314055/original/file-20200206-43079-1u32hbe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/314055/original/file-20200206-43079-1u32hbe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/314055/original/file-20200206-43079-1u32hbe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/314055/original/file-20200206-43079-1u32hbe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/314055/original/file-20200206-43079-1u32hbe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/314055/original/file-20200206-43079-1u32hbe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A silver bullet genetic fix is still elusive for most diseases.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/little-girl-hospital-91838105">drpnncpptak/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Since common serious diseases are rarely caused by single-gene mutations, they cannot be cured by replacing the mutated gene with a normal copy, the premise for gene therapy. <a href="https://doi.org/10.1126/science.aan4672">Gene therapy</a> has gradually progressed in research along a very bumpy path, which has included accidentally causing <a href="https://doi.org/10.1016/j.ymthe.2006.03.001">leukemia</a> and <a href="https://doi.org/10.1093/jnci/92.2.98">at least one death</a>, but doctors recently have been successful treating <a href="https://doi.org/10.1126/science.aan4672">some rare diseases</a> in which a single-gene mutation has had a large effect. Gene therapy for rare single-gene disorders is likely to succeed, but must be tailored to each individual condition. The enormous cost and the relatively small number of patients who can be helped by such a treatment may create insurmountable financial barriers in these cases. For many diseases, gene therapy may never be useful.</p>
<h2>A new era for biologists</h2>
<p>The Human Genome Project has had an enormous impact on almost every field of biological research, by spurring technical advances that facilitate fast, precise and relatively inexpensive sequencing and manipulation of DNA. But these advances in research methods have not led to dramatic improvements in treatment of common debilitating diseases. </p>
<p>Although you cannot bring your genome card to your next doctor’s appointment, perhaps you can bring a more nuanced understanding of the relationship between genes and disease. A more accurate understanding of disease causation may insulate patients against unrealistic stories and false promises.</p>
<p>[ <em>You’re smart and curious about the world. So are The Conversation’s authors and editors.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=youresmart">You can read us daily by subscribing to our newsletter</a>. ]</p><img src="https://counter.theconversation.com/content/130568/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ari Berkowitz receives funding from the National Science Foundation.</span></em></p>Genome sequencing technologies have transformed biological research in many ways, but have had a much smaller effect on the treatment of common diseases.Ari Berkowitz, Presidential Professor of Biology; Director, Cellular & Behavioral Neurobiology Graduate Program, University of OklahomaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1251502019-10-15T12:35:33Z2019-10-15T12:35:33ZMost genetic studies use only white participants – this will lead to greater health inequality<figure><img src="https://images.theconversation.com/files/296897/original/file-20191014-135513-1h0o4lk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Genetic studies need to be more diverse.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/742602847?src=Rar9QUkjLx6LcVOH8Vz7Vg-1-1&size=medium_jpg">Rawpixel/Shutterstock</a></span></figcaption></figure><p>Few areas of science have seen such a dramatic development in the last decade as genomics. It is now possible to read the genomes of millions of people in so-called genome-wide association studies. These studies have identified <a href="https://www.ebi.ac.uk/gwas/diagram">thousands of small differences in our genome</a> that are linked to diseases, such as cancer, heart disease and mental health. </p>
<p>Most of these genetic studies use data from white people – <a href="https://doi.org/10.1016/j.cell.2019.08.051">over 78%</a> of participants are of European descent. This doesn’t mean that they represent Europe. In fact, only <a href="https://doi.org/10.1038/s42003-018-0261-x">three nationalities</a> make up most of the participants: the US, UK, and Iceland. Even though the UK and the US have very diverse populations, their non-white citizens have rarely been included in genetic research. </p>
<p>In recent years, efforts to collect multi-ethnic data have increased. One example is the <a href="https://www.ukbiobank.ac.uk/">UK Biobank</a>, a collection of data from half a million British people accessible to any bona fide researcher. It includes some 35,000 DNA samples from people who are either non-European or “mixed-race”. Yet 92% of research papers on UK Biobank only used the data from the European-descent samples. So collecting data doesn’t automatically solve the problem of non-white representation in research. </p>
<p>The under-representation of non-European groups is problematic for scientific and ethical reasons. The effects of gene variants that are present only in the unstudied groups remain unknown, which means <a href="https://doi.org/10.1038/ng.3620">important clues about the causes of diseases might be missed</a>. Such undiscovered genes would not be included when testing for genetic diseases. So a person carrying one of them could wrongly get a negative genetic test result and might be told that they are not at increased risk of developing the disease. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-the-genomics-health-revolution-is-failing-ethnic-minorities-86385">How the genomics health revolution is failing ethnic minorities</a>
</strong>
</em>
</p>
<hr>
<p><a href="https://doi.org/10.1038/s41467-019-12026-7">Our recent work</a> also shows that existing genetic findings might not apply equally to non-European populations. We found that some gene variants predicting high cholesterol in white populations do not lead to the same heart problems in people from rural Uganda. These findings should serve as a major warning to the field of genetics – one cannot blindly apply findings from ancestrally European groups to everyone else.</p>
<h2>Moral responsibility</h2>
<p>It is important to support the global application of research because scientists have a moral responsibility to develop science for the benefit of the whole of humanity, not restricted by ethnic, cultural, economic or educational boundaries. Some 80% of the world’s population live in low and middle-income countries where healthcare and research are constrained by limited financial and human resources. We should not overlook this part of the world.</p>
<p>Studying different populations has advanced the medical field for everyone’s benefit. For example, the first disease gene mapped in humans was <a href="https://doi.org/10.1038/306234a0">the gene for Huntington’s disease in 1983</a>, identified through examining a large population of patients in villages surrounding Lake Maracaibo in Venezuela. The area was found to have the largest concentration of Huntington’s disease sufferers in the world, which helped them to find the gene. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/297088/original/file-20191015-98670-nprfpc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/297088/original/file-20191015-98670-nprfpc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/297088/original/file-20191015-98670-nprfpc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/297088/original/file-20191015-98670-nprfpc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/297088/original/file-20191015-98670-nprfpc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/297088/original/file-20191015-98670-nprfpc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/297088/original/file-20191015-98670-nprfpc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">People who live around Lake Maracaibo in Venezuela have a much higher risk of developing Huntington’s disease.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/1037548282?src=UYgg0paL1Fgm7C0crUkadQ-1-30&size=medium_jpg">Sunsinger/Shutterstock</a></span>
</figcaption>
</figure>
<p>More recently, a study of <a href="https://www.nature.com/articles/s41380-019-0517-y">schizophrenia</a> found new risk genes by using African and Latino American samples. Genetic risk scores based on results from these groups improved the ability to predict who would develop schizophrenia in all ethnic groups.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/decolonise-science-time-to-end-another-imperial-era-89189">Decolonise science – time to end another imperial era</a>
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</em>
</p>
<hr>
<p>Two things need to happen if we want to avoid increasing health disparities and instead share the medical benefits of genomic science across countries and ethnic groups. First, we need more large diverse studies. First steps in this direction are being taken by the <a href="https://doi.org/10.2147/PGPM.S141546">Human Hereditary and Health in Africa Initiative</a>. <a href="https://doi.org/10.1038/s41586-019-1310-4">PAGE</a> and <a href="https://allofus.nih.gov/about/about-all-us-research-program">All of Us</a> are paving the way to recruit more diverse ethnic groups in the US, and <a href="https://doi.org/10.1093/ije/dyz174">East London Genes and Health</a> focuses on people of South Asian origin in London. </p>
<p>And second, to make sure diverse ethnic data resources are widely used by researchers, the challenges of analysing genetic data from ancestrally diverse samples need to be addressed. While there are <a href="https://doi.org/10.1016/j.cell.2019.08.051">statistical solutions</a>, more work is needed to make them easy to use and give clear guidance about the best approach.</p>
<p>Understanding how genetic risk and social inequality interact to influence disparities in disease risk and outcomes will be critical to improving public health for all.</p><img src="https://counter.theconversation.com/content/125150/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Roseann Peterson receives funding from the National Institutes of Health (grant 1K01MH113848-01A1) and The Brain & Behavior Research Foundation (grant 28632). </span></em></p><p class="fine-print"><em><span>Evangelos Vassos and Karoline Kuchenbaecker do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Genome-wide association studies are more like genome white association studies.Karoline Kuchenbaecker, Associate Professor, Psychiatry, UCLEvangelos Vassos, Senior Clinical Research Fellow, Psychiatry, King's College LondonRoseann Peterson, Assistant Professor, Statistical Geneticist, Virginia Commonwealth UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1134632019-03-13T19:11:18Z2019-03-13T19:11:18ZExperts call for halt to CRISPR editing that allows gene changes to pass on to children<figure><img src="https://images.theconversation.com/files/263553/original/file-20190313-86713-uwtcri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">CRISPR is a gene editing tool that can create permanent changes in the human genome. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/newborn-baby-first-many-small-hospital-1103569475">from www.shutterstock.com</a></span></figcaption></figure><p>Remember the global outrage four months ago at world-first claims a researcher had used the gene editing tool CRISPR to <a href="https://theconversation.com/researcher-claims-crispr-edited-twins-are-born-how-will-science-respond-107693">edit the genomes of twin girls</a>? </p>
<p>The molecular scissors known as CRISPR (<a href="https://theconversation.com/what-is-crispr-gene-editing-and-how-does-it-work-84591">CRISPR/cas9</a> in full) allow scientists to modify DNA with high precision and greater ease than previous technologies.</p>
<p>Now researchers from the USA, Europe, China and New Zealand have published a prominent call for <a href="https://www.nature.com/articles/d41586-019-00726-5">a moratorium</a>, or temporary freeze, on the clinical use of germline gene editing technology in humans. (Germline editing means the genes that are edited are included in eggs and sperm, the “germ” cells, and can be passed on to following generations). </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-crispr-gene-editing-and-how-does-it-work-84591">What is CRISPR gene editing, and how does it work?</a>
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</p>
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<p>The authors on the Nature report include some leaders in the development of CRISPR technologies, as well as bioethicists.</p>
<p>They propose a framework in which nations commit to not approve any clinical use of heritable gene editing unless some conditions are met on technical, societal, medical and ethical grounds. </p>
<p>In that process, they also argue that there should be an initial period during which no clinical use of germline editing is allowed at all. Research would still be allowed, provided embryos are used only in the very early stages in laboratory studies, and not transferred to a woman’s uterus to develop further. They suggest this period could last five years.</p>
<p>After this initial period, any participating country could allow a particular application of germline editing by following three steps: </p>
<ol>
<li>public notice of intent</li>
<li>transparent evaluation and justification of the application (considering not only the scientific and medical aspects, but also the related societal and ethical issues)</li>
<li>achievement of a broad consensus in the nation that this is an acceptable application.</li>
</ol>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/researcher-claims-crispr-edited-twins-are-born-how-will-science-respond-107693">Researcher claims CRISPR-edited twins are born. How will science respond?</a>
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</em>
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<h2>It’s about more than just science</h2>
<p>It is important that the evaluation considers not only the science of germline genetic modifications, but also the broader societal context. The authors mention the risk of discrimination, peer and marketing pressure, and unequal access to the technology if gene editing became available as a tool, for example in IVF clinics.</p>
<p>This moratorium would be limited to human germline editing only. This means modifying human sperm, eggs or embryos to make children whose DNA has been altered. Such changes pass through the generations, which is why germline editing is a particular area of concern. </p>
<p>The moratorium would not apply to changes in human cells not capable of reproduction (called somatic gene editing). <a href="https://www.nature.com/articles/d41587-018-00003-2">Current efforts to treat blindness, sickle cell disease or cancer using CRISPR</a> would not be affected by the moratorium. </p>
<h2>Implications in Australia</h2>
<p>In Australia, germline genetic modification is not allowed, and is illegal.</p>
<p>According to the <a href="https://www.legislation.gov.au/Details/C2017C00306">Prohibition of Human Cloning for Reproduction Act (2002)</a> researchers can face up to 15 years in jail for modifying “the genome of a human cell in such a way that the alteration is heritable by descendants of the human whose cell was altered”. Therefore the implications for Australia will be limited, and applying the initial five-year freeze on any clinical use of germline editing would be seamless. </p>
<p>If Australia wishes to allow any clinical application of germline editing at some point in the future, this act would need to be revised. </p>
<p>The framework proposed in the moratorium call provides a basis for how such a revision could then be discussed: public notice, transparent and comprehensive consideration of the application, and national discussion. </p>
<h2>Voluntary and pragmatic</h2>
<p>The proposed moratorium is voluntary. This is a pragmatic approach. It would be very difficult to get international agreement on a ban. </p>
<p>As the authors note, <a href="https://www.nature.com/articles/palcomms201719">discussions on a legally binding convention to outlaw human cloning are not making much progress</a>. </p>
<p>In the absence of a binding agreement, a voluntary pledge can start to move the main stakeholders towards a workable solution. Other issues such as climate change have shown the limitations of international agreements, but even getting a limited number of countries on board would be a positive first step.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/designer-babies-wont-be-common-anytime-soon-despite-recent-crispr-twins-108342">'Designer' babies won't be common anytime soon – despite recent CRISPR twins</a>
</strong>
</em>
</p>
<hr>
<h2>Change requires commitment</h2>
<p>The authors also call on those who work in fields where CRISPR is used, including the leaders of research institutes as well as individual researchers, to publicly pledge to the principles of the framework they have outlined. </p>
<p>It will be interesting to see how some other stakeholders respond. For instance, will funding agencies and scientific publishers come on board? One objection to moratoriums is that they do not prevent “rogue” entities or individuals from operating outside their framework. </p>
<p>If it was clear that no study would be funded or published unless it adhered to the principles of advance notice, full transparency and national approval, it would remove some of the incentives that sometimes turn scientific research into a race.</p>
<p>Ultimately, in each country, society as a whole will have to decide whether germline editing is acceptable, and under which circumstances. A meaningful consensus will only be achieved if an informed discussion takes place. </p>
<p>To date, issues around gene editing have been <a href="http://www.nationalacademies.org/gene-editing/2nd_summit/">mostly discussed among experts</a>. More than ever, engagement and education that includes diverse members of our society around advanced biotechnologies is crucial.</p><img src="https://counter.theconversation.com/content/113463/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dimitri Perrin has received funding from the Australian Research Council (ARC), the Australian-French Association for Innovation and Research (AFRAN), and the Advance Queensland programme.</span></em></p><p class="fine-print"><em><span>Gaetan Burgio receives funding from the National Health and Medical Research Council (NHMRC), the Australian Research Council (ARC), the National Collaborative Research Infrastructure Strategy (NCRIS) via the Australian Phenomics Network (APN) and the Natural Science Foundation in China (NSFC). </span></em></p>Four months ago a researcher claimed he had used the tool CRISPR to edit the genomes of twin girls. Now prominent researchers and ethicists are calling for a temporary halt to this sort of work.Dimitri Perrin, Senior Lecturer, Queensland University of TechnologyGaetan Burgio, Geneticist and Group Leader, The John Curtin School of Medical Research, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1081682018-12-19T19:09:09Z2018-12-19T19:09:09ZDNA from ancient Aboriginal Australian remains enables their return to Country<figure><img src="https://images.theconversation.com/files/248598/original/file-20181204-23261-d9e96q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Indigenous Australians must be involved in research around provenance and country. Here, representatives of the Willandra Aboriginal Elders visit the Griffith University ancient DNA laboratory. </span> <span class="attribution"><span class="source">Renee Chapman </span>, <span class="license">Author provided</span></span></figcaption></figure><p><em>This article was coauthored by Gimuy Yidniji Traditional Owner Gudju Gudju Fourmile.</em></p>
<hr>
<p>For many decades Aboriginal Australians have campaigned for the return of ancestral remains that continue to be stored in museums worldwide. </p>
<p>But in many instances these remains cannot be repatriated – as their geographic origin, tribal affiliation or language group was never identified. Without this information it is impossible for museums to determine appropriate custodians, which prevents their return.</p>
<p>Our research, published in <a href="http://advances.sciencemag.org/content/4/12/eaau5064">Science Advances today</a>, shows it is possible to determine the origin of Aboriginal Australian remains using DNA-based methods, enabling their return to Country. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/dna-reveals-a-new-history-of-the-first-australians-65344">DNA reveals a new history of the First Australians</a>
</strong>
</em>
</p>
<hr>
<h2>Collaborative beginnings</h2>
<p>Past injustices due to actions and policies implemented in <a href="https://theconversation.com/sorry-isnt-the-hardest-word-so-say-it-for-the-stolen-generations-7079">early colonial history</a> have left gaps in the self-knowledge of many contemporary Aboriginal Australians. </p>
<p>A key term in this context is “Country”: the place in which an Aboriginal Australian, or his or her ancestors, was born and lived. For some communities their Country encompasses large geographical areas; for others it is much smaller. </p>
<p>Aboriginal Australians believe they have a spiritual connection to their Country – and many believe that in order for their ancestor’s spirits to rest, their remains must be returned to Country.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/248597/original/file-20181204-23267-11ayhld.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/248597/original/file-20181204-23267-11ayhld.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=424&fit=crop&dpr=1 600w, https://images.theconversation.com/files/248597/original/file-20181204-23267-11ayhld.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=424&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/248597/original/file-20181204-23267-11ayhld.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=424&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/248597/original/file-20181204-23267-11ayhld.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=533&fit=crop&dpr=1 754w, https://images.theconversation.com/files/248597/original/file-20181204-23267-11ayhld.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=533&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/248597/original/file-20181204-23267-11ayhld.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=533&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The Lake Mungo World Heritage Site has a long history of Aboriginal occupation.</span>
<span class="attribution"><span class="source">Sherene Lambert (St Augustine's College, Ipswich, Australia)</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Many of our traditional owner collaborative partners wanted to learn more about their history through DNA analyses – and to directly test whether DNA might help with the return of <a href="https://theconversation.com/the-violent-collectors-who-gathered-indigenous-artefacts-for-the-queensland-museum-96119">unprovenanced remains</a> from museums worldwide to Country.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-violent-collectors-who-gathered-indigenous-artefacts-for-the-queensland-museum-96119">The violent collectors who gathered Indigenous artefacts for the Queensland Museum</a>
</strong>
</em>
</p>
<hr>
<p>Our research, undertaken in collaboration with Aboriginal Australian traditional owners and communities across Australia, tested whether it is possible to determine the origins of ancient individuals using DNA-based methods. </p>
<p>We successfully recovered ten nuclear genomes (DNA from cell nuclei) and 27 mitogenomes (DNA from cell <a href="https://theconversation.com/explainer-what-are-mitochondria-and-how-did-we-come-to-have-them-83106">mitochondria</a>) from ancient pre-European Aboriginal Australians dating up to 1,540 years before present – and for whom we had records of Country. </p>
<p>These ancient genomic sequences, of known origin, were used as proxies for unprovenanced remains. We compared these against reference datasets of contemporary Aboriginal Australian nuclear and mitochondrial genomes. </p>
<p>Previously the only authentic pre-European DNA ever recovered from Aboriginal Australian remains was the mitochondrial genome of an <a href="https://theconversation.com/new-dna-study-confirms-ancient-aborigines-were-the-first-australians-60616#comment_1264911">ancient man from the Willandra Lakes region</a>. Here we show it is also possible to recover ancient nuclear genomes from Aboriginal Australian remains, despite DNA survival in an Australian context being poor due to harsh climatic conditions.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/250907/original/file-20181217-185255-1nybssg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/250907/original/file-20181217-185255-1nybssg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/250907/original/file-20181217-185255-1nybssg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=529&fit=crop&dpr=1 600w, https://images.theconversation.com/files/250907/original/file-20181217-185255-1nybssg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=529&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/250907/original/file-20181217-185255-1nybssg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=529&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/250907/original/file-20181217-185255-1nybssg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=665&fit=crop&dpr=1 754w, https://images.theconversation.com/files/250907/original/file-20181217-185255-1nybssg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=665&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/250907/original/file-20181217-185255-1nybssg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=665&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Details of the locations and language groups of Aboriginal Australian samples uses in this study. Yellow shading indicates the distribution and location of Pama-Nyungan language families. Orange shading indicates the distribution of non–Pama-Nyungan language families. Dashed lines show the approximate distribution of accepted major language subgroups, with language names in italics. Red symbols indicate previously published mitochondrial or nuclear genomes; blue symbols indicate new unpublished data. Circles indicate contemporary Aboriginal Australian samples, and stars represent ancient individuals. Sample code abbreviations have been included in parentheses.</span>
<span class="attribution"><a class="source" href="http://advances.sciencemag.org/">Joanna Groom/Science Advances</a>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<h2>Mitochondrial vs nuclear DNA</h2>
<p>We found by using maternally inherited DNA (mitochondrial DNA), we could successfully determine the origins of 62.1% of bodily remains of ancient Aboriginal Australians included in this research. </p>
<p>But we could not achieve this for the remaining 37.9% of the remains in the study. For these, the results were either inconclusive (due to a lack of contemporary matches or the matches identified were widespread across large geographic distances), or the results were unreliable. In two instances, the closest contemporary matches were not from the same geographic location, but some 635 kilometres away. </p>
<p>As the return to place and Country of ancestral remains is important to many Aboriginal Australian communities, repatriation to incorrect Country would be extremely problematic. Therefore, we are unable to recommend the use of mitochondrial DNA alone for repatriation.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-dreamtime-science-and-narratives-of-indigenous-australia-95919">The Dreamtime, science and narratives of Indigenous Australia</a>
</strong>
</em>
</p>
<hr>
<p>Nuclear DNA (DNA inherited from both parents) provided the most accurate results, working in 100% of cases and to precise geographic locations. </p>
<p>The results obtained were supported by several different methods, each of which independently showed considerable population structure and local continuity between both the ancient and contemporary populations in each geographic location. </p>
<p>However, when combined, these analyses provide strong evidence that nuclear DNA, as a tool for repatriation, is very effective. If applied to unprovenanced ancestral remains, we believe this will greatly assist with their repatriation. </p>
<h2>A need for national consultation and standards</h2>
<p>Traditional Owner Gudju Gudju Fourmile of the Gimuy Yidniji People of Cairns told us this was an important result, and a solution to a problem that has been a major concern to Aboriginal Australians for more than 50 years. He said: </p>
<blockquote>
<p>Many of our ancestors still remain on foreign land, and in storage of museums and collectors. We need to do the right thing to bring them home so their spirit will rest. </p>
</blockquote>
<p>Despite our success, however, one question remains unanswered: how should this new tool be implemented? We believe that before DNA is used to facilitate repatriation of ancient remains, a detailed set of standards and protocols should be developed as best practice for museums and other institutions to follow. </p>
<p>As this method requires the destruction of unprovenanced ancient bone, albeit in small quantities, it is imperative that these standards be developed in close consultation with Indigenous communities across Australia. It is essential that a consensus be reached and a decision made by Aboriginal Australians at a national level. This requires a national debate, but it should be among our First People.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/new-dna-study-confirms-ancient-aborigines-were-the-first-australians-60616">New DNA study confirms ancient Aborigines were the First Australians</a>
</strong>
</em>
</p>
<hr>
<h2>From subject to researcher</h2>
<p>In addition to developing an effective tool for provenancing ancestral remains for repatriation, this research is significant because it was driven by Aboriginal Australian Traditional Owners and their communities. Their desire to learn more about themselves developed into a major research project in which they were actively involved and equal partners in the direction the research took. </p>
<p>Without their input and knowledge this research would not have been possible. </p>
<p>This is a significant shift from Aboriginal Australians being scientific subjects, as they were in the past, to them becoming researchers in their own right.</p><img src="https://counter.theconversation.com/content/108168/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Lambert receives funding from the Australian Research Council, and Human Frontier Science, and the Marsden Fund (NZ). </span></em></p><p class="fine-print"><em><span>Joanne Wright and Sally Wasef do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Museums around the world hold remains of Aboriginal people that were often taken without permission and in the absence of accurate records. New DNA methods may help return these items to country.Joanne Wright, Research associate, Griffith UniversityDavid Lambert, Professor of Evolutionary Biology, Griffith UniversitySally Wasef, Research Fellow, Griffith UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1078072018-11-28T11:40:40Z2018-11-28T11:40:40ZTension as scientist at centre of CRISPR outrage speaks at genome editing summit<figure><img src="https://images.theconversation.com/files/247685/original/file-20181128-32180-1c4j5ay.png?ixlib=rb-1.1.0&rect=1299%2C0%2C2598%2C1856&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Jiankui He claims he has used CRISPR to edit the genomes of twin girls. </span> <span class="attribution"><span class="source">Merlin Crossley</span>, <span class="license">Author provided</span></span></figcaption></figure><p>I am currently at the <a href="http://www.nationalacademies.org/gene-editing/2nd_summit/index.htm">Second International Summit on Human Genome Editing</a>, where controversial CRISPR scientist Jiankui He presented his research just a few hours ago. He also answered questions from gene experts Robin Lovell-Badge (Crick Institute) and Matt Porteus (Stanford), plus assembled audience members and the media. </p>
<p>It’s just two days since <a href="https://www.technologyreview.com/s/612458/exclusive-chinese-scientists-are-creating-crispr-babies/">reports first aired</a> that Jiankui He had <a href="https://theconversation.com/researcher-claims-crispr-edited-twins-are-born-how-will-science-respond-107693">used CRISPR to edit human embryos</a>, and that twin girls, Lulu and Nana, had been born. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/researcher-claims-crispr-edited-twins-are-born-how-will-science-respond-107693">Researcher claims CRISPR-edited twins are born. How will science respond?</a>
</strong>
</em>
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<hr>
<p>The mood of the meeting is tense. Before these reports, there had been confidence among those in the field that the world was moving as one – cautiously inching forward with CRISPR gene editing technology. </p>
<p>But suddenly the forbidden fruit has been plucked, and some even worry that public confidence may falter.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/247672/original/file-20181128-32230-cy6sjt.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/247672/original/file-20181128-32230-cy6sjt.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247672/original/file-20181128-32230-cy6sjt.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247672/original/file-20181128-32230-cy6sjt.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247672/original/file-20181128-32230-cy6sjt.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247672/original/file-20181128-32230-cy6sjt.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247672/original/file-20181128-32230-cy6sjt.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Jiankui He arrives to speak at the 2nd International Summit on Genome Editing, Hong Kong November 28, 2018.</span>
<span class="attribution"><span class="source">Merlin Crossley</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Jiankui He focused on removing a gene called CCR5, critical for the HIV virus to enter cells. He aimed to mimic a natural mutation which confers resistance to HIV. This work is now on hold and an uncomfortable international discussion has begun. </p>
<p>The stories, and a <a href="https://www.youtube.com/watch?v=th0vnOmFltc&feature=youtu.be">video published by Jiankui He</a> in which he explains the apparent work, have created <a href="https://theconversation.com/worlds-first-gene-edited-babies-premature-dangerous-and-irresponsible-107642">widespread condemnation</a> on <a href="https://theconversation.com/why-we-are-not-ready-for-genetically-designed-babies-107756">scientific and ethical grounds</a>.</p>
<p>If the claims are correct, and they are certainly plausible, this is the first time CRISPR has been used to create permanent changes in human genomes – changes that would be passed on to future generations. </p>
<p>Jiankui He himself is experienced in using CRISPR – he first carried out pilot experiments in mice, monkeys, and then non-viable human embryos. He also says he carried out a genomic analysis on the embryos before implantation, and that he had enrolled and worked with a further six couples in this trial before it was paused. One of the additional women may be in the very early stages of pregnancy. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/worlds-first-gene-edited-babies-premature-dangerous-and-irresponsible-107642">World's first gene-edited babies? Premature, dangerous and irresponsible</a>
</strong>
</em>
</p>
<hr>
<h2>International consensus</h2>
<p>China is a major scientific power. The capability of Chinese researchers is highly respected, but if the international consensus on being transparent and cautious about gene editing does not hold the future is difficult to predict. </p>
<p>Jiankui He’s host institution – the Southern University of Science and Technology – <a href="https://www.sustc.edu.cn/news_events_/5524">published a statement</a> saying he had been on leave at the time of the trial and that it was not conducted at their institution. </p>
<p>Currently other Chinese researchers in attendance at the conference are among the strongest critics of this work. Several have indicated that it breaks the rules governing genetic research in China. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/247675/original/file-20181128-32203-12knrb9.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/247675/original/file-20181128-32203-12knrb9.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247675/original/file-20181128-32203-12knrb9.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247675/original/file-20181128-32203-12knrb9.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247675/original/file-20181128-32203-12knrb9.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247675/original/file-20181128-32203-12knrb9.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247675/original/file-20181128-32203-12knrb9.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Robin Lovell-Badge (Crick Institute), Jiankui He and Matt Porteus (Stanford) prepare to talk on stage.</span>
<span class="attribution"><span class="source">Merlin Crossley</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Be that as it may, the results seem clear. Today’s presentation suggests this was a thoroughly planned and executed project, where Jiankui He carefully communicated his results, first by <a href="https://www.youtube.com/watch?v=th0vnOmFltc&feature=youtu.be">video</a>, and then followed up with his conference talk to share his data. Details on the process, the specific mutations and analysis used to screen for potentially harmful “off-target” genomic changes were also presented today. </p>
<p>On the data shown, it does look like genome editing was achieved. Though the actual mutations did not end up mimicking naturally occurring mutations in CCR5, so we can’t tell – and indeed may never know - whether the twins are resistant to HIV. </p>
<p>He also indicated the work had been submitted for publication in a peer reviewed journal. </p>
<h2>Many questions</h2>
<p>Hosting panel members Robin Lovell-Badge and Matt Porteus asked questions of Jiankui He after he had finished presenting – the whole presentation and the Q&A is available for viewing <a href="https://livestream.com/NASEM/events/8464254/videos/184103056">here</a>. </p>
<p>The Chair of the Summit, Nobel Laureate <a href="https://www.nobelprize.org/prizes/medicine/1975/baltimore/facts/">David Baltimore</a>, spoke from the floor after the panel session. He expressed concerns that the work did not comply with the commitments made at the first Gene Editing Summit held three years ago, whereby:</p>
<blockquote>
<p>it would be irresponsible to proceed with any clinical use of germ line editing unless and until the safety issues had been dealt with. </p>
</blockquote>
<p>He added:</p>
<blockquote>
<p>I don’t think it has been a transparent process. We only found out about it after it’s happened and after the children are born. I personally don’t think that it’s medically necessary. </p>
</blockquote>
<p>And further: </p>
<blockquote>
<p>I think there’s been a failure of self-regulation by the scientific community because of a lack of transparency.</p>
</blockquote>
<p>He emphasised these comments came entirely from himself. </p>
<p>A statement from the organisers of the summit will be released tomorrow, and I expect it will re-iterate the need for caution, openness in planning and full transparency. </p>
<p>And, despite the shock, that’s what I hope we’ll get – ultimately CRISPR technology is slow, expensive and is used at the level of individuals not populations. </p>
<p>There won’t be a tsunami but there will be plenty to discuss. And we will have time, just as we did when other expensive medical landmarks occurred - heart transplants, test tube babies, and somatic gene therapy. This is bigger, but I believe we can still get back to a consensus and find the right path.</p><img src="https://counter.theconversation.com/content/107807/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Merlin Crossley works for UNSW, receives funding from ARC and NHMRC, is on the Trust of the Australian Museum, Chair of the Board of UNSW Press, and Deputy Chair of the Australian Science Media Centre</span></em></p>The world seemed to be inching forward with CRISPR gene editing technology – but suddenly the forbidden fruit has been plucked, and some even worry that the CRISPR tree has been cut down.Merlin Crossley, Deputy Vice-Chancellor Academic and Professor of Molecular Biology, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1003552018-09-24T12:36:30Z2018-09-24T12:36:30ZShould we edit the genomes of human embryos? A geneticist and social scientist discuss<figure><img src="https://images.theconversation.com/files/235664/original/file-20180910-123110-1sjjjpb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/group-multiethnic-babies-crawling-isolated-on-144900358?src=1eUR-dDDVFwjE22c02M5GA-1-22">Sirtravelalot/Shutterstock.com</a></span></figcaption></figure><p><em>This is an article from <a href="https://theconversation.com/uk/topics/head-to-head-62019">Head to Head</a>, a series in which academics from different disciplines chew over current debates. Let us know what else you’d like covered – all questions welcome. Details of how to contact us are at the end of the article.</em></p>
<p><strong>Felicity Boardman</strong>: The birth of a child with genetic disease is generally an unexpected event. The parents of these children typically won’t have a family history with the condition, or even be aware that they are genetic “carriers”: that they can transmit a genetic condition to their offspring, but do not have it themselves. Indeed, there are currently only two carrier screening programmes active in the UK that are implemented during pregnancy (one for for thalassaemia, and the other for sickle cell trait). So for most parents, discovering the condition in their family occurs through their child’s diagnosis, either through the <a href="https://www.nhs.uk/conditions/pregnancy-and-baby/newborn-blood-spot-test/">newborn heel prick test</a>, or following the onset of symptoms. </p>
<p>Even in cases where a genetic condition in the foetus is identified during pregnancy, the options for would-be parents remain extremely limited. Many of the most common genetic conditions still lack effective treatments or cures. This means that, for many parents, the information leads to a decision about whether or not to terminate the pregnancy, or continue in the knowledge that the child will have the condition.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/237127/original/file-20180919-158213-1pdwaq9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/237127/original/file-20180919-158213-1pdwaq9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=390&fit=crop&dpr=1 600w, https://images.theconversation.com/files/237127/original/file-20180919-158213-1pdwaq9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=390&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/237127/original/file-20180919-158213-1pdwaq9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=390&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/237127/original/file-20180919-158213-1pdwaq9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=490&fit=crop&dpr=1 754w, https://images.theconversation.com/files/237127/original/file-20180919-158213-1pdwaq9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=490&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/237127/original/file-20180919-158213-1pdwaq9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=490&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Sickled red blood cells in liver tissue.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/x3e4ekce?query=Sickle+cell+disease">SB Lucas/Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The introduction of <a href="https://theconversation.com/scientists-edit-human-embryos-to-safely-remove-disease-for-the-first-time-heres-how-they-did-it-81925">genome editing</a>, however, signals a dramatic departure from this usual pathway through reproductive care. Although the foundations of genome editing were laid initially in the 1960s when proteins were first used to “cut” DNA, the recent development of new techniques and technologies (such as <a href="https://theconversation.com/uk/topics/crispr-15704">CRISPR-Cas9</a>) has made genome editing more precise, more cost-effective and consequently more accessible than ever before. </p>
<p>By intervening before a child is even born, the use of genome editing in human reproduction has the potential to alleviate some of the complicated and painful decisions around pregnancy termination – by providing a reproductive option that has, up until now, not been possible. That is, the possibility of removing the disease-causing genetic variant, while simultaneously preserving the life of the foetus. </p>
<p><strong>Helen O’Neill</strong>: Genome editing indeed marks a significant shift, and not only in the area of reproduction, but also in the direction of tailored treatments and personalised medicine. It offers hope to those who, before now, have not had any better options than prescriptions and palliative care.</p>
<p>It’s an incredibly exciting time for such research both in terms of discovery and diagnostics. The advent of CRISPR genome editing has catapulted previous efforts in genomics and is being adopted globally. My research, for example, uses CRISPR genome editing to assess the treatment and understanding of sex chromosome disorders and neuromuscular disorders. There are <a href="https://theconversation.com/why-treat-gene-editing-differently-in-two-types-of-human-cells-51843">two ways</a> in which genome editing could be used for both treatment and prevention: somatic cell therapy, which could be used in newborns and adults, and germline genome editing, which would be used in an early embryo to prevent a disorder. In this second type, genome editing would aim to alter every cell of a resulting baby, and therefore these changes would be passed on to future generations, meaning that disease causing variants would be prevented from being passed on.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/237120/original/file-20180919-158213-7115hv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/237120/original/file-20180919-158213-7115hv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/237120/original/file-20180919-158213-7115hv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/237120/original/file-20180919-158213-7115hv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/237120/original/file-20180919-158213-7115hv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/237120/original/file-20180919-158213-7115hv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/237120/original/file-20180919-158213-7115hv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">CRISPR-Cas9 allows scientists to target and activate or silence specific genes.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/dna-molecule-structure-strand-repair-editing-774492757?src=fsLzr20sTEzmuh_eWpHdWg-1-10">Vrx/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>The use of genetic technologies in reproduction is <a href="https://www.theguardian.com/commentisfree/2017/aug/04/editing-human-genome-consumer-eugenics-designer-babies">frequently criticised</a> for harbouring <a href="https://theconversation.com/three-person-ivf-has-nothing-to-do-with-eugenics-but-its-time-for-a-designer-baby-debate-23996">eugenic undertones</a>. But genetic selection occurs with or without these technologies. For example, we make decisions about the genetics of our future offspring when we choose our mate. We make decisions about the health of our future offspring when we take supplements such as <a href="https://theconversation.com/folic-acid-in-pregnancy-mthfr-gene-explains-why-the-benefits-may-differ-95302">folic acid</a> and improve our diet during pregnancy. Decades of research have yielded <a href="https://theconversation.com/complex-guidelines-on-eating-fish-when-pregnant-mean-that-mothers-and-babies-are-missing-out-83587">ever-increasing information</a> about how we can protect and nurture our embryos, not only by including essential macronutrients but also by excluding harmful exposures such as alcohol and tobacco. We don’t ignore these welfare warnings. Nor is it considered elitist to adhere to them by choice to deliver a healthy baby.</p>
<p>But when comparing these genetic prompts to more purposeful permutations of our genetics using gene editing technology, the rationalisation for wanting a healthy baby somehow becomes displaced with irrational ideas about the creation of a “perfect” baby.</p>
<p>It is true that advances in research rarely lend themselves so quickly to clinical adoption. But safety is obviously the number one prerequisite for any research development to become medical practice. Proceeding with such medical advances will always be subject to rigorous oversight. So <a href="https://www.newscientist.com/article/2179920-revealed-what-the-uk-public-really-thinks-about-the-future-of-science/">for many</a>, genome editing – and the era of <a href="https://theconversation.com/personalised-medicine-has-obvious-benefits-but-has-anyone-thought-about-the-issues-59158">personalised medicine</a> – is not something to be feared but embraced.</p>
<h2>Mistrust and myth</h2>
<p><strong>FB</strong>: While caution is a good thing, fear of the technologies can make meaningful and progressive debate quite difficult. The association of genome editing with “<a href="https://theconversation.com/why-the-case-against-designer-babies-falls-apart-45256">designer babies</a>”, for example, although making for catchy headlines, masks the intended uses of the technologies. The connotations of frivolity, commercialism and superficial decision making that comes with the term “designer” does a great disservice to the parents in these difficult situations who are facing complex and often deeply painful decisions.</p>
<p><strong>HON</strong>: Yes: the term “designer” suggests that there is an element of choice and privilege to a baby that may be born with an edited genome. In fact, the opposite is more likely to be true; people will not edit the genomes of their embryos out of choice, but because they have no choice if they are to deliver a healthy, viable baby.</p>
<p>And as it stands, <a href="https://www.nature.com/articles/d41586-018-05462-w">we are still debating</a> the number of genes in the human genome and certainly do not know what all of the genes do. Even if we did, the unpredictability in the mechanism of genetic crossover between parental genomes precludes any realistic control or prediction of the majority of traits. Choosing partners based on what we see on the outside is a far more reliable method for designing our babies’ appearance.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/237728/original/file-20180924-85785-1y6nasc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/237728/original/file-20180924-85785-1y6nasc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=373&fit=crop&dpr=1 600w, https://images.theconversation.com/files/237728/original/file-20180924-85785-1y6nasc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=373&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/237728/original/file-20180924-85785-1y6nasc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=373&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/237728/original/file-20180924-85785-1y6nasc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=469&fit=crop&dpr=1 754w, https://images.theconversation.com/files/237728/original/file-20180924-85785-1y6nasc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=469&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/237728/original/file-20180924-85785-1y6nasc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=469&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">All babies are ‘designed’ to some extent when we choose a partner.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/parents-their-newborn-baby-boy-on-729856267?src=XHAK_BLe7vsMGnO_t72a9w-1-0">Jacob Lund/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>There is no doubt that a subject like this needs widespread discussion and debate and in fact <a href="https://www.newscientist.com/article/2179920-revealed-what-the-uk-public-really-thinks-about-the-future-of-science/">recent surveys</a> show that the public are optimistic about genome editing for curing diseases, but there can also be a lack of trust about the intended use of this technology. The distraction from the good that this technology can do is frustrating as a researcher. We should not extrapolate the worst possible outcome which encourages unrealistic and disingenuous ideas focusing on dystopian scenarios.</p>
<p><strong>FB</strong>: I think some of this mistrust stems from fear of the unknown and a concern that this technology stands to alter not only our biology, but also our society. People with genetic disabilities, for example, those with spinal muscular atrophy, haemophilia and <a href="https://theconversation.com/discovering-the-ancient-origin-of-cystic-fibrosis-the-most-common-genetic-disease-in-caucasians-100499">cystic fibrosis</a> (who I work with during my research), are set to be impacted by the consequences of genome editing, yet they are not always included in stakeholder debates as much as they could be. This is in spite of the fact that people with disabilities have much to contribute to our understanding of what life with genetic disease is really like. Insights that are highly relevant to decisions about which conditions are suitable candidates for genome editing.</p>
<p><strong>HON</strong>: But the use of genome editing can also be seen as addressing some of the objections to prenatal testing and pregnancy termination raised by disability rights supporters. By treating the foetus’ or embyro’s condition, rather than terminating them, genome editing may be an attractive alternative for those who disagree with pregnancy termination or embryo disposal on the grounds of disability or otherwise. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/237114/original/file-20180919-158219-1ogp1mi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/237114/original/file-20180919-158219-1ogp1mi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=661&fit=crop&dpr=1 600w, https://images.theconversation.com/files/237114/original/file-20180919-158219-1ogp1mi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=661&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/237114/original/file-20180919-158219-1ogp1mi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=661&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/237114/original/file-20180919-158219-1ogp1mi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=830&fit=crop&dpr=1 754w, https://images.theconversation.com/files/237114/original/file-20180919-158219-1ogp1mi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=830&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/237114/original/file-20180919-158219-1ogp1mi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=830&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Separation of DNA fragments.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/gkhb2nrc?page=3&query=DNA">Guy Tear/Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>What’s at stake?</h2>
<p><strong>FB</strong>: That’s of course true, but for some, this development is regarded as coming at a cost. Genome editing not only changes the genome of the embryo it treats, but also that of every generation that comes after it, and so critical questions still remain about how and when it would be ethically and socially appropriate to implement it. Indeed, it <a href="http://nuffieldbioethics.org/project/genome-editing-human-reproduction">has been suggested</a> that over time, genome editing could effectively remove particular disease-causing traits from the human gene pool.</p>
<p>While this may seem a positive development to many people, the question of which conditions and traits genome editing should be used to treat, and which it should not, is far from straightforward. <a href="https://www.ncbi.nlm.nih.gov/pubmed/30196552">Research I have conducted</a> with families living with a range of conditions that could all one day be candidate conditions for genome editing, for example, has revealed that a person’s relationship to their genetic condition is often complex. For some, their disability is an integral and valued part of their identity, while for others, an unwelcome burden. As such, ascertaining the quality of life of a person with a genetic disorder (particularly before birth) is a near impossible task.</p>
<p>As genome editing technologies move into mainstream healthcare and become widely adopted, it is possible that would-be parents will feel under pressure to use them. This is a concern that has long been raised in relation to informed consent and antenatal screening <a href="https://www.ncbi.nlm.nih.gov/pubmed/20947230">for Down’s Syndrome</a>. The potential stigmatisation and branding of parents who forgo the technologies as “selfish” or “irresponsible” needs to be seriously considered, as well as the possibility that this stigma could extend to the disabled people already living with “editable” conditions (the numbers of whom are likely to reduce over time).</p>
<p>Indeed, the public profile of these (often rare) genetic conditions will shift and alter through the use of genome editing – from conditions once considered “chance” occurrences, to preventable diseases. This change is likely to have social consequences, as well as biological ones.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/237284/original/file-20180920-129877-1b14sjq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/237284/original/file-20180920-129877-1b14sjq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=375&fit=crop&dpr=1 600w, https://images.theconversation.com/files/237284/original/file-20180920-129877-1b14sjq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=375&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/237284/original/file-20180920-129877-1b14sjq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=375&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/237284/original/file-20180920-129877-1b14sjq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=472&fit=crop&dpr=1 754w, https://images.theconversation.com/files/237284/original/file-20180920-129877-1b14sjq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=472&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/237284/original/file-20180920-129877-1b14sjq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=472&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Fibrous deposits in pancreas due to cystic fibrosis.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/sbbr52xk?query=cystic+fibrosis">Anne Clark, University of Oxford/Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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</figure>
<p><strong>HON</strong>: It is essential to put genome editing in context with what is already available in terms of screening and pre-implantation genetic diagnosis – which has been available for 30 years. With this, every single condition needs to be appraised and legally approved before it can be tested for. And ultimately, the decision comes from the parents.</p>
<p>It is also important to remember that we cannot predict the pattern of genetics or the heritability of disorders. So suggesting that conditions would be “eliminated” is certainly not the goal of researchers, nor is it realistic. Not all genetic disorders are inherited from the family line, many are sporadic or “<a href="https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/de-novo-mutation"><em>de novo</em></a>” mutations which occur through chance. While germline genome editing certainly has consequences for future generations, many current standard treatments are not ideal and have unwanted side effects, but they are the best we currently have. Take for example cancer radiation therapy, which not only alters, but destroys, the germline.</p>
<p>More research is critical. We know less about the early developmental stages of a human embryo than we do of mice, worms, flies and fish. Knowledge is the most powerful prescription you can give, but it comes with a burden. It is important that with each new discovery we are able to fully consolidate our knowledge before advancing to the next level in research.</p>
<p><strong>FB</strong>: I agree – and also think it’s important to note that we need more research that explores the technologies from a range of vantage points. Currently, there is a lack of dialogue between the various disciplines working in this area, including geneticists, scientists, bioethicists, sociologists and disability studies scholars. By removing some of the disciplinary divisions, we may better be able to see the full consequences of the technologies for everyone whose lives will be affected by them, the list of which seems to be ever-expanding.</p>
<hr>
<p><em>If there’s a specific topic or question you’d like experts from different disciplines <a href="https://theconversation.com/uk/topics/head-to-head-62019">to discuss</a>, you can:</em></p>
<p><em>* Email your question to josephine.lethbridge@theconversation.com
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<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Academics from different disciplines come Head to Head in this series to tackle topical debates.Felicity Boardman, Assistant Professor in Social Science and Systems in Health, University of WarwickHelen O'Neill, Lecturer in Reproductive and Molecular Genetics, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1000072018-07-16T20:10:25Z2018-07-16T20:10:25ZCRISPR/Cas9 gene editing scissors are less accurate than we thought, but there are fixes<figure><img src="https://images.theconversation.com/files/227712/original/file-20180716-27018-7adbus.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">We need to know gene editing technology is precise before we try to use it to cure diseases.</span> <span class="attribution"><span class="source">from www.shutterstock.com</span></span></figcaption></figure><p><a href="https://theconversation.com/what-is-crispr-gene-editing-and-how-does-it-work-84591">CRISPR</a> gene editing technology is revolutionising medicine and biology. This technique allows scientists to edit DNA with more precision and greater ease than previous gene editing technology.</p>
<p>But a <a href="https://www.nature.com/articles/Nbt.4192">new study</a> has called into question the precision of the technique.</p>
<p>The hope for gene editing is that it will be able to cure and correct diseases. To date, many successes have been reported, including curing <a href="https://www.nature.com/articles/nature25164">deafness in mice</a>, and in altering cells to <a href="http://stm.sciencemag.org/content/10/449/eaao3240">cure cancer</a>.</p>
<p>Some <a href="https://clinicaltrials.gov/ct2/results?cond=&term=crispr&cntry=&state=&city=&dist=">17 clinical trials</a> in human patients are registered testing gene editing on leukaemias, brain cancers and sickle cell anaemia (where red blood cells are misshaped, causing them to die). Before implementing CRISPR technology in clinics to treat cancer or congenital disorders, we must address whether the technique is safe and accurate.</p>
<h2>How does CRISPR work again?</h2>
<p>CRISPR technology utilises molecular scissors (a bacteria enzyme called “Cas9”) to cut the DNA we want to target, and then we can paste DNA in to replace what we have removed. Cas9 recognises a specific segment of DNA among the entire human genome by utilising a guide, something like a map, that is linked to Cas9. </p>
<p><iframe id="tc-infographic-229" class="tc-infographic" height="560px" src="https://cdn.theconversation.com/infographics/229/1e1ccd9abbd9a92604e144561050c08a9c49d8b3/site/index.html" width="100%" style="border: none" frameborder="0"></iframe></p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-crispr-gene-editing-and-how-does-it-work-84591">What is CRISPR gene editing, and how does it work?</a>
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<p>Cas9 can persist in the body for several hours to several weeks. While it remains in the body, Cas9 can cut and paste other segments of DNA (“off targets”) or the targeted segment of DNA over and over (“on target”).</p>
<h2>What the new study found</h2>
<p>A study published today in <a href="https://www.nature.com/articles/Nbt.4192">Nature Biotechnology</a> explores the accuracy of the Cas9 scissors. Scientists at the Sanger Institute at Cambridge, UK sought to determine whether Cas9’s cut and paste process is accurate enough to be safely used in humans for treating disease.</p>
<p>To answer this important question, they examined in detail the DNA segments in mouse embryonic stem cells and human cells near the segment that was cut to see if they were affected.</p>
<p>They found that after the DNA was repaired (new DNA pasted into the “cut” segment), the scissors continued to cut the DNA over and over again. They found significant areas near the cut site where DNA had been removed, rearranged or inverted.</p>
<p>If a fragment of DNA is removed or inverted (the genes switched around), the gene modification could be dangerous, and even lead to disease. While this seems scary, this could potentially be overcome using new sequencing technologies. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/human-embryo-crispr-advances-science-but-lets-focus-on-ethics-not-world-firsts-81956">Human embryo CRISPR advances science but let's focus on ethics, not world firsts</a>
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<h2>Can we use different scissors?</h2>
<p>There are a few options for getting around this problem. One option is to isolate the cells we wish to edit from the body and reinject only the ones we know have been correctly edited.</p>
<p>For example, lymphocytes (white blood cells) that are crucial to killing cancer cells could be taken out of the body, then modified using CRISPR to heighten their cancer-killing properties. The DNA of these cells could be sequenced in detail, and only the cells accurately and specifically gene-modified would be selected and delivered back into the body to kill the cancer cells.</p>
<p>While this strategy is valid for cells we can isolate from the body, some cells, such as neurons and muscles, cannot be removed from the body. These types of cells might not be suitable for gene editing using Cas9 scissors.</p>
<p>Fortunately, researchers have discovered other forms of CRISPR systems that don’t require the DNA to be cut. Some CRISPR systems only cut the RNA, not the DNA (DNA contains genetic instructions, RNA convey the instructions on how to synthesise proteins).</p>
<p>As RNA remains in our cells only for a specific period of time before being degraded, this would allow us to control the timing and duration of the CRISPR system delivery and reverse it (so the scissors are only functional for a short period of time). </p>
<p>This was found to be successful for <a href="https://www.sciencedaily.com/releases/2018/03/180315122940.htm">dementia in mice</a>. Similarly, some CRISPR systems simply change the letters of the DNA, rather than cutting them. This was successful for specific mutations causing diseases such as <a href="https://www.nature.com/articles/d41586-017-08722-3">hereditary deafness in mice</a>.</p>
<p>In short, before using CRISPR clinically, we still have a lot to learn about the effects of Cas9 scissors in the cells. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/debate-on-whether-we-should-use-gene-editing-technology-is-far-from-black-and-white-51483">Debate on whether we should use gene-editing technology is far from black and white</a>
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<img src="https://counter.theconversation.com/content/100007/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gaetan Burgio receives funding from the National Health and Medical Research Council (NHMRC), the Australian Research Council (ARC), the National Collaborative Research Infrastructure Strategy (NCRIS) via the Australian Phenomics Network (APN) and the Natural Science Foundation in China (NSFC). </span></em></p>A new study found the Cas9 gene editing scissors don’t stop cutting after we tell them to.Gaetan Burgio, Geneticist and Group Leader, The John Curtin School of Medical Research, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/964162018-05-11T03:46:04Z2018-05-11T03:46:04ZCriminals can’t easily edit their DNA out of forensic databases<figure><img src="https://images.theconversation.com/files/218540/original/file-20180511-34021-smzq3t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">You're knicked - and so is your DNA. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/home">from www.shutterstock.com </a></span></figcaption></figure><p>There have been a number of <a href="http://www.dailymail.co.uk/news/article-5696383/Criminals-manipulate-DNA-avoid-detection-police-databases.html">news articles</a> over the last week or so reporting that to avoid being matched to criminal forensic databases, criminals could <a href="https://www.telegraph.co.uk/science/2018/05/05/criminals-could-alter-dna-evade-justice-new-genetic-editing/">edit their genomes</a> using cheap, online kits. </p>
<p>What seems to be at the centre of these articles, and giving them a sense of credibility, are some quotes from <a href="http://arep.med.harvard.edu/gmc/">George Church</a> – a highly respected geneticist from Harvard.</p>
<p>Asked if CRISPR could alter DNA to the extent it would make forensic evidence unusable, Church reportedly <a href="https://www.telegraph.co.uk/science/2018/05/05/criminals-could-alter-dna-evade-justice-new-genetic-editing/">told The Telegraph</a>: </p>
<blockquote>
<p>We could do that today, easily. A lot of it is done by blood and even if you just get a stem cell transplant you have a new identity.</p>
<p>I could imagine there being an industry.</p>
</blockquote>
<p>But is it really so easy? From our perspective there may be some confusion around what is feasible, and what is actually happening now. Let’s unpack some of the issues and think about what would be required to pull off such a feat.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/from-the-crime-scene-to-the-courtroom-the-journey-of-a-dna-sample-82250">From the crime scene to the courtroom: the journey of a DNA sample</a>
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<h2>Evading forensic databases</h2>
<p>The <a href="https://theconversation.com/from-the-crime-scene-to-the-courtroom-the-journey-of-a-dna-sample-82250">mainstay of modern DNA identification</a> is short tandem repeat (STR) markers, which are small sections of DNA that vary by length (the number of repeats). Multiple STR markers are used to create a DNA profile. </p>
<p>Most systems now use a panel of 24 DNA markers, but some will allow partial matches of as few as eight or nine markers. It might be possible, in theory, to cheat the system by changing only one of these markers, but in practice a hypothetical DNA-edited criminal would probably want to change several of them. </p>
<p>STR markers are located in the more variable parts of our genome and this may make them more difficult to accurately target with gene editing tools. The easiest way to change your STR profile would probably be to delete some DNA and make the length of that marker shorter.</p>
<p>Technology for reading DNA is getting better, and DNA forensics is currently moving from STR markers to systems that look at more of our DNA and can tell us <a href="https://theconversation.com/dna-facial-prediction-could-make-protecting-your-privacy-more-difficult-94740">much more about someone</a>. </p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/dna-facial-prediction-could-make-protecting-your-privacy-more-difficult-94740">DNA facial prediction could make protecting your privacy more difficult</a>
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<p>In the recent <a href="https://theconversation.com/how-cops-used-a-public-genealogy-database-in-the-golden-state-killer-case-95842">Golden State killer case</a>, so-called “SNP chips” – that measure around 600,000 sites in our genome – were used to make matches to genealogy databases. DNA forensics is a moving field and a future criminal may have to edit much more of their DNA to evade this sort of matching. </p>
<p>But how much of your body would you need to change to avoid detection? Is it just the cells that are used for sampling – for example your cheek cells, your blood cells – or every cell in your body?</p>
<p>As George Church seems to point out, in theory a genetic manipulation to your blood (or another targeted area) could allow a criminal to be excluded as a suspect. In the Golden State killer case, police used “discarded” DNA from the suspect’s trash. To fully <a href="http://www.frontlinegenomics.com/news/22616/how-close-criminals-evading-justice-using-crispr/">evade DNA forensics</a> you would therefore likely have to make much more extensive changes (i.e. skin, semen, hair, blood, cheek cells).</p>
<p>Let’s look at the techniques that might be used by someone wanting to alter their DNA. </p>
<h2>Editing genes with CRISPR</h2>
<p><a href="https://theconversation.com/what-is-crispr-gene-editing-and-how-does-it-work-84591">CRISPR</a> or CRISPR/Cas9, is a method for making precise edits to a genome.</p>
<p><iframe id="tc-infographic-229" class="tc-infographic" height="560px" src="https://cdn.theconversation.com/infographics/229/1e1ccd9abbd9a92604e144561050c08a9c49d8b3/site/index.html" width="100%" style="border: none" frameborder="0"></iframe></p>
<p>For CRISPR to work it has to be delivered into cells. There are a number of ways to do this, but no one has published an effective way to change all of the cells in your body. Doing so is currently a formidable challenge.</p>
<p>It’s difficult to know exactly where we are with CRISPR in humans. There have been reports that the <a href="https://www.nature.com/articles/d41586-018-00335-8">human immune system</a> may attack the Cas9 enzyme required for CRISPR to work. </p>
<p>Human trials involving CRISPR are only just starting in western countries. <a href="https://www.wsj.com/articles/china-unhampered-by-rules-races-ahead-in-gene-editing-trials-1516562360">China</a> has conducted tests, but most of these involve removing immune cells, <a href="https://www.gizmodo.com.au/2018/01/china-has-already-gene-edited-86-people-with-crispr/">editing them</a> and putting them back.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-crispr-gene-editing-and-how-does-it-work-84591">What is CRISPR gene editing, and how does it work?</a>
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<p>There are reports that CRISPR doesn’t always modify all cells, and if criminals actually start using these kinds of techniques then law enforcement is going to be more alert to “mixed signal” samples.</p>
<h2>Dangers of biohacking</h2>
<p>The <a href="http://www.the-odin.com/diy-crispr-kit/">CRISPR Kit</a> linked to in a Daily Mail article is from ODIN, a company that is part of the “DIY Bio” movement. The specific kit mentioned is designed to let someone edit bacteria. </p>
<p>The CEO of ODIN – <a href="http://www.the-odin.com/about-us/">Josiah Zayner</a> – has, however, previously <a href="https://www.theatlantic.com/science/archive/2018/02/biohacking-stunts-crispr/553511/">injected himself with CRISPR DNA</a> that would enhance his muscles. At best this stunt is unlikely to work, and at worst could be quite damaging.</p>
<p>Community involvement in biology isn’t a bad thing, but modifying your own genome using CRISPR really isn’t something you should be doing at home on yourself. We don’t yet fully understand how this gene editing technology might affect other parts of our genome. </p>
<p>The US Food and Drug administration has highlighted that <a href="https://www.technologyreview.com/s/609568/biohackers-disregard-fda-warning-on-diy-gene-therapy/">DIY gene therapy is illegal and risky</a>. The legality may not concern a criminal, but the potential for off-target effects should.</p>
<h2>Stem cell replacement</h2>
<p>Another way to change your genetic code is stem cell replacement. This has a precedent with some people that have had stem cell or bone marrow transplants. </p>
<p><a href="https://www.elynsgroup.com/journal/j-for-med-leg-aff/article/chimerism-in-humans-after-bone-marrow-transplantation-a-new-challenge-for-forensic-dna-experts">Studies</a> have looked at the DNA in cells of people who have received donor stem cells. </p>
<p>They report both donor and recipient DNA – this is known as “chimerism”, two different genomes – from many types of tissue and fluid, including mouthwash, oral swabs, and fingernails, sometimes years after stem cell transplants have taken place. </p>
<p>Hair follicles were thought to be unaffected by chimerism, but the genetic material from the Y chromosome of male donors has been <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578715/">detected in hair follicles</a> of female recipients in <a href="https://www.nature.com/articles/bmt201027">at least two studies</a>, suggesting that bone marrow replacement could affect much more of your body than originally thought.</p>
<p>So varying your DNA through stem cells is feasible, but as noted by Church: </p>
<blockquote>
<p>CRISPR actually would be easier than a stem cell transplant because (a transplant) would have to be done sterilely and you would need to irradiate yourself to get rid of the old ones. </p>
</blockquote>
<p>Changing out all of your bone marrow would be an extreme medical procedure.</p>
<h2>What can we learn from this?</h2>
<p>Changing your DNA profile to evade criminal databases is technically possible but it seems highly unlikely that criminals are actually doing this now. It probably wouldn’t even be effective with a DIY-bio kit. If any criminals are inspired to try and CRISPR themselves we would strongly recommend that they don’t.</p>
<p>George Church may have been speaking about what is possible in a somewhat hypothetical sense, and his quotes may have been taken out of context in some media coverage. </p>
<p>Sensationalised or not, this story is a useful thought exercise that reminds us how the world as we know it could change as the code of life starts to become re-writable.</p><img src="https://counter.theconversation.com/content/96416/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A bit of advice for any criminals inspired to try and edit their own genes – it’s unlikely to work, and it may present health risks.Caitlin Curtis, Research fellow, Centre for Policy Futures (Genomics), The University of QueenslandJames Hereward, Research fellow, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/957852018-05-03T03:15:05Z2018-05-03T03:15:05ZA DNA test says you’ve got Indigenous Australian ancestry. Now what?<figure><img src="https://images.theconversation.com/files/216969/original/file-20180501-135837-1ocfg5o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Families have secrets - and sometimes we don't know our complete genetic histories. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/vintage-photos-family-archive-shot-beginning-46788088?src=NrskIcPo5iSekbL9okj_cw-1-33">from www.shutterstock.com </a></span></figcaption></figure><p><em>Technologies for amplifying, sequencing and matching DNA have created new opportunities in genomic science. In this series <a href="https://theconversation.com/au/topics/when-dna-talks-53134">When DNA Talks</a> we look at the ethical and social implications.</em> </p>
<hr>
<p>Getting your “DNA done” is all the rage in the United States.</p>
<p>The sensationalism started with celebrities such as <a href="https://www.youtube.com/watch?v=MsEZBSTc3a0">Jessica Alba</a> and <a href="https://www.youtube.com/watch?v=Exz0yNdvksg">Snoop Dog</a> – and has now spread to hundreds of video bloggers disclosing their ancestry to <a href="https://www.youtube.com/watch?v=_5-GwlAVS3w">drum rolls</a>, <a href="https://www.youtube.com/watch?v=pK7bLFfzLwo">exclamations</a>, <a href="https://www.youtube.com/watch?v=b0EDNX47S20">cheers</a> and <a href="https://www.youtube.com/watch?v=MdpuGIZfR90">tears</a>. </p>
<p>These tests claim to reveal deep ancestral origins, and many public users of this technology are black Americans seeking information about their African roots. </p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/Exz0yNdvksg?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Snoop Dog sent his DNA to be tested – and did the maths faster than this TV host.</span></figcaption>
</figure>
<p>The uptake of direct-to-consumer genetic testing has been slower in Australia. Here it is <a href="https://theconversation.com/dna-nation-raises-tough-questions-for-indigenous-australians-59877">complicated by debates</a> both beyond and within the Indigenous community – with some leaders calling for greater scrutiny to prevent “<a href="http://www.theaustralian.com.au/national-affairs/indigenous/push-for-aboriginal-id-tests-by-indigenous-leaders/news-story/a0bd39a868ad44a22dab85cf76cb9dc7">fakes</a>” or “<a href="http://www.theaustralian.com.au/national-affairs/indigenous/brawl-over-wannabe-and-tickabox-aborigines/news-story/d4a8a3a47cf478d08a17b7c466d09e66">wannabes</a>” calling themselves Indigenous.</p>
<p>One of the authors of this article – Shaun Lehmann – was dropped into this debate inadvertently, after receiving the result of his own DNA test a few years ago. </p>
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Read more:
<a href="https://theconversation.com/dna-nation-raises-tough-questions-for-indigenous-australians-59877">DNA Nation raises tough questions for Indigenous Australians</a>
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<h2>Professional and personal</h2>
<p>Shaun had more professional reasons for doing the test than most: at the time he was lecturing in human genetic diversity at the Australian National University and wanted to use his own genetic data as teaching tool.</p>
<p>He also had personal questions about his maternal grandmother, who had died when he was a small child. She had grown up without her mother and said little about her background.</p>
<p>Because they are related through a direct maternal line, Shaun knew that it was his grandmother, and by extension mysterious great-grandmother, who gave him his <a href="https://www.sciencedirect.com/science/article/pii/S0005272898001613">mitochondrial genome</a>.</p>
<p>Mitochondria are the tiny organelles that make energy in our cells. While the genome in the nucleus of our cells – our 23 pairs of chromosomes – is made up of a mix of our biological mother’s and father’s DNA, the relatively small mitochondrial genome is passed down through the egg and so reflects a single line of maternal ancestors.</p>
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Read more:
<a href="https://theconversation.com/explainer-what-are-mitochondria-and-how-did-we-come-to-have-them-83106">Explainer: what are mitochondria and how did we come to have them?</a>
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<p>What Shaun didn’t know at the time, and what the test revealed, was that his particular mitochondrial genome fell into a haplogroup (a grouping of similar mitochondrial genomes) called “S2”, which has <a href="https://onlinelibrary.wiley.com/doi/full/10.1002/9780470015902.a0020815.pub2">only been observed in Aboriginal Australians</a>.</p>
<h2>Interpreting genetic results</h2>
<p>Being mitochondrial DNA, Shaun knew exactly where to look in his genealogy to find out more. Sure enough, he soon found records that his grandmother’s maternal family were Aboriginal people originally from the Albany area of Western Australia. With this information in hand, Shaun was able to trace his family tree to living <a href="https://www.noongarculture.org.au/">Noongar</a> relatives.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/217371/original/file-20180502-153873-lchl0i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/217371/original/file-20180502-153873-lchl0i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/217371/original/file-20180502-153873-lchl0i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=511&fit=crop&dpr=1 600w, https://images.theconversation.com/files/217371/original/file-20180502-153873-lchl0i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=511&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/217371/original/file-20180502-153873-lchl0i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=511&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/217371/original/file-20180502-153873-lchl0i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=642&fit=crop&dpr=1 754w, https://images.theconversation.com/files/217371/original/file-20180502-153873-lchl0i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=642&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/217371/original/file-20180502-153873-lchl0i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=642&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">How mitochondrial DNA and nuclear DNA are passed on.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Mitochondrial_DNA_versus_Nuclear_DNA.gif">Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Shaun’s discovery was certainly aided by the fact that he is a geneticist and could interpret his DNA test results. Most important, though, was that his Aboriginal ancestry happened to be in the direct maternal line. </p>
<p>Mitochondrial DNA is a reliable source of genetic information about Aboriginal ancestry, but it can’t help at all if your Aboriginal ancestors sit anywhere else in your family tree. That is, it’s only useful to track direct from mother to grandmother to great grandmother and so on.</p>
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Read more:
<a href="https://theconversation.com/friday-essay-when-did-australias-human-history-begin-87251">Friday essay: when did Australia’s human history begin?</a>
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<h2>Different kinds of DNA tests</h2>
<p>Most of the “ethnic breakdown” DNA results being shared publicly by bloggers come from testing companies that compare their nuclear DNA with material from various ethnic groups. The tests focus on variations in specific regions of genes – known as single nucleotide polymorphisms, or SNPs. </p>
<p>To our knowledge, DNA testing companies do not currently have reliable reference SNP data from Indigenous Australians. </p>
<p><a href="http://www.dnatribes.com/">One company</a> offering tests claiming to identify Indigenous Australians uses an approach that compares sequences in genes known as <a href="https://www.nature.com/scitable/topicpage/forensics-dna-fingerprinting-and-codis-736">Short Tandem Repeats, or STRs</a>. STR data from around the world are widely available in the forensic science literature because these are widely used in <a href="https://www.sciencedirect.com/science/article/pii/S1687157X12000194">criminal investigations and paternity testing</a>. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/is-your-genome-really-your-own-the-public-and-forensic-value-of-dna-95786">Is your genome really your own? The public and forensic value of DNA</a>
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<p>Ethical and scientific concerns have been raised about the use of STR data for commercial ancestry testing. For example, it is difficult to know how companies get their <a href="https://theconversation.com/dna-nation-raises-tough-questions-for-indigenous-australians-59877">reference samples</a>. </p>
<p>The case of American blogger <a href="http://lisagarrigues.blogspot.com.au/2011/01/dna-tribes-and-all-my-relations.html">Lisa Garrigues</a> is illustrative. Garrigues did a test back in 2010 – it reportedly gave her second “Highest Resolution Global Population Match” as “European-Aboriginal”.</p>
<p>She was excited by this discovery, but also sceptical – her family has no known connections to the Southern Hemisphere. Lisa and her father subsequently did <a href="http://lisagarrigues.blogspot.com.au/2011/05/">more thorough DNA testing</a>, and it didn’t suggest Aboriginal ancestry. </p>
<p>In our personal correspondence with one of the genetic genealogists who assisted Lisa, <a href="http://isogg.org/wiki/McDonald's_BGA_project">Doug McDonald</a> suggests these kind of inconsistencies are extremely common – STR markers are not designed for ancestry tests, but for matching individual people.</p>
<h2>After the test: now what?</h2>
<p>We need to be on the lookout for misinformation and unethical practices around genealogy testing. But even where the science is reliable, such as Shaun’s mitochondrial DNA test, the implications of identifying genetic Indigenous ancestry are far from clear.</p>
<p>Shaun was proud to learn about his ancestry and has since got in contact with his relatives. He is also looking into his grandmother’s past to find out whether her separation from her mother was influenced by the policies that led to the Stolen Generations. </p>
<p>Existing research suggests there are many possible endings for journeys like Shaun’s. <a href="http://www.podsocs.com/podcast/finding-aboriginal-identity/">Bindi Bennett’s work</a> highlights how young, light-skinned people who had no previous ties to the Aboriginal community can develop a strong Indigenous identity, even in the face of resistance from that community. </p>
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Read more:
<a href="https://theconversation.com/culture-not-colour-is-the-heart-of-aboriginal-identity-30102">Culture, not colour, is the heart of Aboriginal identity</a>
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<p>But <a href="http://librarycatalogue.griffith.edu.au/record=b1357619">Fiona Noble’s 1996 research</a> with Queenslanders who discovered their Aboriginal ancestry late in life suggests many of this demographic see their heritage as extremely important, but not all-defining. </p>
<p>They are more comfortable describing themselves as being “of Aboriginal descent” rather than “Aboriginal”. </p>
<p>As <a href="http://www.borderlands.net.au/vol7no2_2008/ganter_turning.pdf">Regina Ganter notes</a>, the “in-between” status of these “half-steps” is not well-recognised contemporary policy and discourse – which tends to frame Aboriginality as an either/or identity.</p>
<p>Although Noble and Bennett’s research participants discovered their heritage through documents or family stories, not genetics, their work offers a window onto a future where more Australians discover Aboriginal ancestry through DNA tests.</p>
<p>Without a doubt, the inevitable collision of Aboriginal and Torres Strait Islander Australia with direct-to-consumer genetic testing will continue to raise challenging questions about ancestry and identity in the 21st century. </p>
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Read more:
<a href="https://theconversation.com/dna-facial-prediction-could-make-protecting-your-privacy-more-difficult-94740">DNA facial prediction could make protecting your privacy more difficult</a>
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<img src="https://counter.theconversation.com/content/95785/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Emma Kowal receives funding from the Australian Research Council and the National Health and Medical Research Council.</span></em></p><p class="fine-print"><em><span>Elizabeth Watt and Shaun Lehmann do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Ancestry and identity are not the same thing. A scientist tells the story of what happened when he sent his DNA to an ancestry company.Elizabeth Watt, Research Fellow, Deakin UniversityEmma Kowal, Professor of Anthropology, Deakin UniversityShaun Lehmann, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/957862018-05-01T20:17:35Z2018-05-01T20:17:35ZIs your genome really your own? The public and forensic value of DNA<figure><img src="https://images.theconversation.com/files/216973/original/file-20180501-135803-1tfhk4c.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Females who remain unidentified at the time of burial are named 'Jane Doe'. </span> <span class="attribution"><a class="source" href="https://www.findagrave.com/">Findagrave </a></span></figcaption></figure><p><em>Technologies for amplifying, sequencing and matching DNA have created new opportunities in genomic science. In this series <a href="https://theconversation.com/au/topics/when-dna-talks-53134">When DNA Talks</a> we look at the ethical and social implications.</em> </p>
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<p>When Joseph DeAngelo was <a href="https://www.nytimes.com/2018/04/27/us/golden-state-killer-case-joseph-deangelo.html">arrested</a> in the United States last month over a series of 30-year-old murders and assaults, attention quickly focused on how the suspect was found. </p>
<p>In their search for the so-called “Golden State Killer”, police looked for DNA matches on a public genealogy database that people use to build family trees. This approach led police first to a close relative, and then to the suspect.</p>
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<strong>
Read more:
<a href="https://theconversation.com/how-cops-used-a-public-genealogy-database-in-the-golden-state-killer-case-95842">How cops used a public genealogy database in the Golden State Killer case</a>
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<p>Applying genealogical research techniques to forensic DNA analysis is a useful tool in solving cold cases. </p>
<p>However – as many who have traced their family tree would know – genealogy is not for the fainthearted. It is a complex and difficult process, prone to error and misinterpretation. Family trees have been described as “<a href="http://nautil.us/issue/56/perspective/youre-descended-from-royalty-and-so-is-everybody-else">entangled meshes</a>”. </p>
<p>Without expert knowledge, false assumptions can be made and investigative resources wasted. The technique also raises legal, ethical and policy challenges.</p>
<h2>Identifying human remains</h2>
<p><a href="https://www.forensicmag.com/news/2018/04/buck-skin-girl-case-break-success-new-dna-doe-project">In 1981</a>, a woman wearing a buckskin jacket was found murdered on a roadside in Ohio. The unidentified “Buckskin Girl” was buried in a “Jane Doe” grave. While investigators pursued various leads, DNA obtained from retained blood yielded no matches.</p>
<p>In 2018, the <a href="https://dnadoeproject.org/">DNA Doe Project</a> – a new charity applying a technique called “forensic genealogy” to unsolved missing person cases – agreed to work on the case. </p>
<p>Using crowdfunding, the volunteers collected donations to undertake “whole genome” sequencing. This generated <a href="https://www.forensicmag.com/news/2018/04/buck-skin-girl-case-break-success-new-dna-doe-project">enough genetic data</a>, consistent with the markers used by online DNA providers, to allow upload to a public genealogy site.</p>
<p>The search returned a possible first cousin, once removed. By searching that individual’s shared family tree, a presumptive identification was made. The family tree included a comment about a relative: “Death - Unknown Missing - Presumed Dead”. </p>
<p>In a matter of hours, genealogists had provided a solid lead in a 37-year-old case, leading to the identification of the victim as Marcia King.</p>
<p>There are about <a href="https://theconversation.com/australia-has-2-000-missing-persons-and-500-unidentified-human-remains-a-dedicated-lab-could-find-matches-90620">500 sets of unidentified human remains</a> in Australia. Given the success of genealogists at the <a href="https://dnadoeproject.org/">DNA Doe Project</a>, applying this approach could help bring closure to families.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/australia-has-2-000-missing-persons-and-500-unidentified-human-remains-a-dedicated-lab-could-find-matches-90620">Australia has 2,000 missing persons and 500 unidentified human remains – a dedicated lab could find matches</a>
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<h2>Where things can go wrong</h2>
<p>Law enforcement use of forensic genealogical data has not always yielded such results. </p>
<p>In 1996, <a href="http://www.postregister.com/articles/chris-tapp-coverage-featured-news-daily-email/2017/07/29/contradictory-dna-results-put">Angie Dodge was murdered in Idaho</a>. DNA was recovered from the crime scene and, nearly 20 years later, the profile was searched against a genealogy database. A close match was returned and investigators identified that individual’s son, Michael Usry Jr., as a suspect. </p>
<p>However, Usry, who was coincidentally on vacation in Idaho around the time of the murder, later provided a DNA sample and was ruled out as the culprit. <a href="http://www.postregister.com/articles/chris-tapp-coverage-featured-news-daily-email/2017/07/29/contradictory-dna-results-put">Usry says</a> that it took a month to clear his name through DNA. </p>
<p>Search engines still return results linking him to the investigation. While almost all hits make clear that he was eliminated as a suspect, one asks: “Do you think Michael Usry Jr. could be involved in Angie’s murder?”</p>
<h2>Will people be put off genetic testing?</h2>
<p>The potential for online genetic databases to be used to help law enforcement is increasing – the DNA testing market is expected to <a href="https://www.gizmodo.com.au/2018/01/the-consumer-dna-testing-market-is-already-booming-but-its-about-to-explode/">more than triple by 2022</a>, to A$388 million. In 2017, AncestryDNA – the largest provider – reportedly sold 1.5 million test kits in a <a href="https://www.gizmodo.com.au/2018/01/the-consumer-dna-testing-market-is-already-booming-but-its-about-to-explode/">single sales weekend alone</a>.</p>
<p>But use of forensic genealogy also has the potential to undermine consumer trust in genetic testing and online genealogy. </p>
<p>Genetic providers may be more susceptible to consumer backlash about privacy concerns than social media companies such as Facebook, which <a href="http://variety.com/2018/digital/news/deletefacebook-didnt-happen-facebook-grows-users-in-q1-despite-privacy-backlash-beats-earnings-estimates-1202786867/">has continued to grow</a> in spite of recent concerns about its data storage practices. Many users do not find the need to engage with genetic providers on an ongoing basis, like they do with Facebook. After initial testing, users wishing to minimise privacy risks could potentially download their data and then delete their accounts, preventing the company from further using their data.</p>
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<strong>
Read more:
<a href="https://theconversation.com/new-cryptocurrencies-could-let-you-control-and-sell-access-to-your-dna-data-89499">New cryptocurrencies could let you control and sell access to your DNA data</a>
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<p>Genetic providers are also limited in their ability to implement privacy safeguards, such as identity verification, due to the very nature of their products. Individuals may legitimately use the tool without knowing their true birth name or names of family members.</p>
<p>In each of these cases, investigators uploaded of some form of genetic data, of unknown origin, to a public database. This could amount to a breach of a provider’s terms and conditions, but there may be little the company can do to prevent such use.</p>
<h2>We should proceed with caution</h2>
<p>Forensic genealogy is just one example of the growing intelligence value of publicly accessible data. Police have also used social media to track suspects. <a href="https://www.kivitv.com/news/social-media-forensics-coroner-uses-facebook-to-find-victims-next-of-kin">A coroner in Idaho</a> noted that: </p>
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<p>Facebook is not something we thought we’d be using to find next of kin. We use it every single week.</p>
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<p>This kind of law enforcement activity online has been litigated in the past.</p>
<p>In a <a href="https://www.leagle.com/decision/infdco20141217d27">2014 US case</a>, evidence was admitted despite police obtaining access to a social media account by inviting the defendant to accept a fake friend request. Here the defendant explicitly consented, but genealogical websites often promote the sharing of family tree and genetic information, without requiring consent to share with each new connection.</p>
<p>This followed a <a href="https://dockets.justia.com/docket/new-york/nyndce/7:2013cv00752/94686">2013 example</a> where the US Drug Enforcement Administration allegedly created a fake social media account in the name of the owner of a seized mobile phone. In that case, the social media provider wrote demanding <a href="http://money.cnn.com/2014/10/20/technology/security/facebook-dea/">no other fake accounts be created on its platform</a>.</p>
<p>Similar arguments may arise with forensic genealogy. Courts may need to balance the benefits to society of solving crime with whether the user has given implied consent, both for themselves and their relatives.</p>
<p>Privacy legislation may also kick in at the point where a profile is identified, or is reasonably identifiable. When that occurs, the forensic genealogist has created an online genetic profile for a third party, without their consent.</p>
<p>The use of forensic genealogy brings us closer to a point where it may be possible – given enough data and resources – to identify any genetic sample. Crowdsourcing and crowdfunding means this technique is available to all. </p>
<p>Achieving an approach that is privacy compliant, balanced and cautious is essential to maintaining public trust and minimising potential harm. Otherwise individuals who, having parted with $99 and a small vial of saliva, may suddenly find themselves part of a criminal investigation.</p><img src="https://counter.theconversation.com/content/95786/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Research for this article was supported by an Australian Government Research Training Program Scholarship. This article also draws on research funded by the Endeavour Fellowships and Awards, a Department of Education and Training initiative.</span></em></p><p class="fine-print"><em><span>Dennis McNevin has received funding from the Australian Research Council, the Discovery Translation Fund (ANU Connect Ventures), US Army International Technology Center - Pacific and the Australian Institute of Nuclear Science and Engineering.</span></em></p>We’re at the point in DNA technology where individuals who – having parted with $99 and a small vial of saliva – may suddenly find themselves in a criminal investigation.Nathan Scudder, PhD Researcher, University of CanberraDennis McNevin, Professor, University of Technology SydneyLicensed as Creative Commons – attribution, no derivatives.