PNAS has an open-access article describing the current state of knowledge of the genetics of autism. The authors looked at information from the Autism Genetic Resource Exchange and two other databases; one from the University of Michigan, the other from the Interactive Autism Network (IAN) Research Database. Their findings indicated that most cases of autism can be explained by one of two mechanisms. The concluded that most cases arise from spontaneous mutations, with a minority occurring due to a dominant gene.
A unified genetic theory for sporadic and inherited autism
Published online before print July 25, 2007, 10.1073/pnas.0705803104
PNAS | July 31, 2007 | vol. 104 | no. 31 | 12831-12836
Xiaoyue Zhao*, Anthony Leotta*, Vlad Kustanovich{dagger}, Clara Lajonchere{dagger}, Daniel H. Geschwind{ddagger}, Kiely Law§, Paul Law§, Shanping Qiu¶, Catherine Lord¶, Jonathan Sebat*, Kenny Ye||,**, and Michael Wigler*,**
Autism is among the most clearly genetically determined of all cognitive-developmental disorders, with males affected more often than females. We have analyzed autism risk in multiplex families from the Autism Genetic Resource Exchange (AGRE) and find strong evidence for dominant transmission to male offspring. By incorporating generally accepted rates of autism and sibling recurrence, we find good fit for a simple genetic model in which most families fall into two types: a small minority for whom the risk of autism in male offspring is near 50%, and the vast majority for whom male offspring have a low risk. We propose an explanation that links these two types of families: sporadic autism in the low-risk families is mainly caused by spontaneous mutation with high penetrance in males and relatively poor penetrance in females; and high-risk families are from those offspring, most often females, who carry a new causative mutation but are unaffected and in turn transmit the mutation in dominant fashion to their offspring.
At first it might seem counterintuitive that most cases would occur in low-risk families. The explanation is that there are a lot more low-risk families than there are high-risk families.
They note that the mutations occur first in germ-line cells (ova and sperm). This is consistent with the observation that older parents are at higher risk for having children with autism.
In contrast to the highly technical discussion in the PNAS, there is a nice plain-language account of some of the same ideas. It will be published in the New York Times Magazine this coming weekend. It is available now to Times Select members; others have to wait for the weekend, for full text.
What are Austistic Girls Made Of
By EMILY BAZELON
Published: August 5, 2007
The Times article focuses on differences between girls with autism and boys with autism.
...But he agrees with Lainhart that it is easier for Asperger's boys to find other boys -- either on or off the autistic spectrum -- who want to spend hours on their Game Boys or in a realm of Internet fantasy. Klin and Lainhart also say they think that the world is a more forgiving place for boys with the quirks of Asperger's because, like it or not, awkwardness is a more acceptable male trait.
This gender dynamic doesn't necessarily affect girls with Asperger's when they are very young; if anything, they often fare better than boys at an early age because they tend to be less disruptive. In 1993, Catherine Lord, a veteran autism researcher, published a study of 21 boys and 21 girls. She found that when the children were between the ages of 3 and 5, parents more frequently described the girls as imitating typical kids and seeking out social contacts. Yet by age 10, none of the girls had reciprocal friendships while some of the boys did...
...And so girls with autism and normal intelligence may end up at a particular disadvantage...
Bazelon also learned that it is possible that some females with high-functioning autism spectrum disorders have better social skills, thus they may not be recognized as readily:
...But based on their clinical experience, Lainhart and also Skuse see autism as a heterogeneous disorder. Its profile may change and expand as more is understood about girls, whose autism, they worry, often goes undiagnosed. That is partly, Skuse posits, because girls' general aptitude for communication and their social competence helps some Asperger's girls "pass" -- they pick up on their difference and carefully mask it by mimicking other girls' speech and manner and dress. In a sense, their femaleness allows some girls to seem less autistic. It is as if they start off with a social advantage -- Skuse sees this as a 20-point bonus on a scale of 100 -- that helps counter the disorder. This idea isn't necessarily at odds with the findings that show girls to be more seriously affected by autism, Skuse says, because the girls who succeed in masking their deficit wouldn't be included in studies. And so they are missing from the picture. "There is no doubt in my mind that the way we have defined autism currently biases our assessments strongly in the direction of identifying a male stereotype," he says. The C.D.C. agrees and says that as a result the estimate for the number of girls with autism and normal intelligence may be low.
One of the main points in the Times article is that there is a relative lack of research on autism in girls. This is changing, with positive results:
By isolating sex as a variable, scientists are seeing potential genetic hot spots for autism. "By comparing males and females, we will have a much better chance of discovering the causes of autism," says Geraldine Dawson, a psychology professor and director of the University of Washington Autism Center, who was a co-author of one of the studies.
The Times article has some inspiring stories about kids with autism. This is a nice touch. It is something that tends to be lacking in modern academic articles.
UPDATE: the New York Times magazine article now has a permanent link, here.
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