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Mothers' genes may be why autism is more common in boys

Boys are more likely to be diagnosed with neurodevelopmental disorders, such as autism, because girls need more extreme genetic…

Mothers with genetic mutations not harmful to females may be passing them onto their sons. Vincent van der Pas/Flickr (resized), CC BY-SA

Boys are more likely to be diagnosed with neurodevelopmental disorders, such as autism, because girls need more extreme genetic mutations to develop them, according to a study published in the American Journal of Human Genetics today.

“One of the greatest mysteries in child development, is why so many more males are diagnosed with developmental disorders compared to females,“ said Andrew Whitehouse, head of the autism research team at the Telethon Institute for Child Health Research at the University of Western Australia.

Boys are more likely to develop autism spectrum disorders, intellectual disability and attention deficit hyperactivity disorder. The study authors highlight that one girl is diagnosed with autism for every four boys, while 30% more boys have intellectual disability than girls.

Genetics as well as a possible social bias that increases the chances of diagnosis in boys have both been suggested as reasons for the difference. Boys may simply be tested more frequently for such disorders, leading to higher rates of diagnoses.

Jozef Gecz, professor of human genetics at the University of Adelaide, who has previously worked with one of the researchers but was not involved in this study, said although this research doesn’t identify a social explanation for the gender difference in the diagnoses of neurodevelopmental disorders, the social bias might still be a real effect.

“There are historical, religious and social reasons that, to some extent, would lead to more men being identified with such problems,” he said. “While we don’t see as much of this in modern western societies, there are still glimpses of it.”

But the study authors, Sébastien Jacquemont of the University Hospital of Lausanne and with Evan Eichler of the University of Washington School of Medicine, suggest the size of the difference may be attributable to genes.

They analysed DNA samples and sequencing data sets of one group consisting of nearly 16,000 individuals with neurodevelopmental disorders and another with about 800 families affected by autism spectrum disorder. They studied the individual variations in the number of copies of a particular gene as well as sequence variations affecting single genes.

They found females diagnosed with autism or another neurodevelopmental disorder had both a larger number of harmful individual variations and sequence variations than similarly diagnosed males.

“The data indicate that females require greater ‘aetiological burden’ than males – that is, more genetic mutations – for brain development to be knocked off the typical course (as is the case for autism),” said Andrew Whitehouse.

The authors suggest this is because women are more developmentally robust and require more extreme genetic mutations to push them over the diagnostic threshold. Women can accumulate more genetic damage before they present with neurodevelopmental disorders.

“There are good evolutionary reasons to protect women because they’re the ones who carry the species,” said Gecz. “But these females who survive and have children who may then inherit the mutations.”

“Our findings may lead to the development of more sensitive, gender-specific approaches for the diagnostic screening of neurodevelopmental disorders,” Jacquemont told Cell Press, the publisher of American Journal of Human Genetics.

But Gecz said the question of what proportion of the mutations leading to neurodevelopmental disorders coming from mothers remained. He said working out the significance of the mechanism would also have huge ramifications on diagnostic testing.

Whitehouse noted that the next great mystery was to understand why males were more genetically fragile than females.

“Do females have some form of biological ‘shield’ that males do not, which protects against a certain number of genetic mutations during brain development? Or is that males have an additional biological mechanism that females do not, which may increase fragility to genetic mutations?” he asked.

Understanding these questions, may very well get to the very heart of what causes various types of autism and other neurodevelopmental disorders, he said.

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17 Comments sorted by

  1. Bruce Shaw

    Retired Hurt

    No where in this article is there reference to a particular chromosome or gene.

    Is there any relationship between allele variation on the X chromosome?

    1. Reema Rattan

      Health + Medicine Editor at The Conversation

      In reply to Bruce Shaw

      Hi Bruce,

      My understanding is that basically the double X may be giving females an advantage, but the mechanism is not understood as one of the Xs is silent and there are caveats to this inactivation.

      Gene is expression is also influenced by hormones and that may also have a role. All these are still not known as constitute the next step in this field of research as Professor Whitehouse mentions.


    2. Bruce Shaw

      Retired Hurt

      In reply to Reema Rattan

      Thanks for the reply Reema although I was leaning more toward what possible role dominant and recessive alleles may play given females are XX and if mobile genetic elements may have a role.

      In particular are there any instances of transposons, pathogenicity islands etc from mitochondrial DNA inserting into a chromosomal ORF and influencing protein production or as you mention hormones, via gene regulation.

      It would seem obvious to me that if there is more of a genetic link specific to females as opposed to environmental factors than analysis at the molecular level focusing on X, Y or mitochondrial DNA is more likely to provide answers.

  2. Comment removed by moderator.

    1. Bruce Shaw

      Retired Hurt

      In reply to John Crest

      I'm not sure if you have an extra chromosome 21 but I suggest some EST may solve the problem.

  3. Meg Thornton


    To be honest, I suspect the real problem when it comes to things like autism spectrum disorders is that they're strongly gender-identified, both in diagnosis and in definition. It's a "male brain" thing - something boys are more likely to be diagnosed with and allowed to take steps to accommodate. Whereas the same problems in girls are likely to be read as "laziness" or "shyness" or even just bad behaviour, and are more likely to be dealt with via disciplinary means. Basically, our society is…

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    1. Bruce Shaw

      Retired Hurt

      In reply to Meg Thornton

      That's an interesting take on things Meg.

      What do you think about the recent research proposing the possibility of a "Gay" gene?

    2. Bruce Shaw

      Retired Hurt

      In reply to Cory Zanoni

      Thanks Cory,

      Personally from a moral perspective I do not see what all the fuss is about in 2014 and cannot see any reason why there should not be more acceptance of the mantra "live and let live".

      That said, I am interested in the possible genetic link to what has traditionally been thought of as a lifestyle choice.

      I am thankful for the link you provided and will certainly read the research contained within and I trust your provision of this link is not predicated by a perceived notion of irrational fear.

      I am perhaps being a little precious and as such apologize if I may have miss read your assistance.

      Kind Regards

    3. Bruce Shaw

      Retired Hurt

      In reply to Bruce Shaw

      Cory, having read the article only confirms my own thoughts that finding a single gene responsible for behavior is as unlikely as to find a single gene responsible for our preference in music.

      The point of the original question to Meg was to compare her analysis of a genetic link or lack thereof to autism and the analogous situation as it relates to homosexuality.

    4. Sue Ieraci

      Public hospital clinician

      In reply to Meg Thornton

      Meg Thornton - I suspect your thoughts are not mutually exclusive with the findings discussed in the article. Certainly the way we deal with ''outliers'' in behaviour differs between societies and between families. Having tight family structures, strong rules and regimented lives suits some and disadvantages others.

      I suspect you are also spot on about the influence of intelligence and language. A child who ''acts out'' frustration is more likely to be disciplined than a child who is able to verbalise it.

      Having said that, there is no reason why all these family and societal influences wouldn't be occurring on top of the biological ones discussed.

  4. Dale Bloom


    The diagnosis of autism has become important.

    If there has been a marked increase in autism spectrum disorders in recent times, then it is much more likely autism has environmental factors, such as types of nutrients or possible toxins in the diet of the mother when pregnant, or in the diet of new born infants.

    1. Brian McNair

      Professor of Journalism, Media and Communication at Queensland University of Technology

      In reply to Dale Bloom

      the rise in diagnosis of autism does not imply an increase in incidence. Increased public and medical awareness of the condition has heightened sensitivity and improved recognition. In the past autistic people were seen as 'a bit different', or 'eccentric', or 'quirky', etc. Now that the characteristics of the condition (or its many variants) are better understood, diagnosis is 'easier', thus rates are higher. As for maleness of autism - since the diagnosis can be made from age 3 onwards, not sure how social conditioning on gender is relevant. Autism is not 'caused' by environment, conditioning, MMR or other vaccines, or diet. It is present at birth, manifest by early childhood, and can be managed with appropriate educational support and care. It can never be 'cured', because it is not a disease.

    2. Dale Bloom


      In reply to Brian McNair

      I think the jury is still out regards toxins and a possible link to neurological diseases in children.

      “Toxic chemicals may be triggering the recent increases in neurodevelopmental disabilities among children -- such as autism, attention-deficit hyperactivity disorder, and dyslexia -- according to a new study from Harvard School of Public Health (HSPH) and Icahn School of Medicine at Mount Sinai.”

      There is the “male brain” theory of autism suggesting that autism is an extreme form of maleness, but I think that theory was designed to denigrate men, or designed to be popular by denigrating men.

      There is another possibility that “Autism affects different parts of the brain in females with autism than males with autism”

  5. Donald Newgreen

    Research Group Leader

    The X-chromosome is a large gene rich chromosome. Some have suggested it hold more than its share of genes affecting brainfunction (though you always have to be sceptical about 'loaded' information like that). Males have one copy and that's what they must use. Females have two copies, with one randomly inactivated in each cell (more or less). Their X-chromosome- influenced functions may be an average of the two particular variants they have for each gene on the X. Hence 'two copy persons' are less likely to express extremes than 'one copy persons', fewer (not none) will be near the edge in any function influenced by genes on the X. Having two copies of a large chromosome may confer to females a greater genetic resilience, but the net effect may not be huge because X-genes are acting along with all the genes on all the rest of the chromosomes where both sexes have two copies.