Evidence for gene-autism link just published

The new study identifies 27 loci that have rare copy number variations, where there are more or fewer repeated DNA segments than expected, common to the genomes of several children with autism spectrum disorder. These variations are not present in controls without autism spectrum disorder.

The peer reviewed paper is available in the Open Access journal PLoS Genetics.

ResearchBlogging.orgThe sample included 2,832 individuals distributed among 912 families that had multiple autistic children. The control group consisted of 1,070 samples of disease-free children who presumably are not clustered from a smaller number of family groups.

Note the apparent imbalance in sample size. Actually, it is not as big of a difference as one might think, as the 2,832 individuals samples do not represent 2,832 cases because they come from a set of under 1,000 families. In effect, the sample size of autism-related individuals in 912.

Aside from the variable regions, the study also discovered two novel genetic alleles that may be related to autism, BZRAP1 and MDGA2, which are related to synaptic function and neurological development, respectively. It is important to note that suspect alleles of these genes were passed down in some, but not all, of the affected individuals in families.

From the author's summary:

Autism spectrum disorders (ASDs) are common neurodevelopmental syndromes with a strong genetic component. ASDs are characterized by disturbances in social behavior, impaired verbal and nonverbal communication, as well as repetitive behaviors and/or a restricted range of interests. To identify genes likely to contribute to ASD etiology, we performed high density genotyping in 912 multiplex families from the Autism Genetics Resource Exchange (AGRE) collection and contrasted results to those obtained for 1,488 healthy controls. To enrich for variants most likely to interfere with gene function, we restricted our analyses to deletions and gains encompassing exons. Of the many genomic regions highlighted, 27 were seen to harbor rare variants in cases and not controls, both in the first phase of our analysis, and also in an independent replication cohort comprised of 859 cases and 1,051 controls. More work in a larger number of individuals will be required to determine which of the rare alleles highlighted here are indeed related to the ASDs and how they act to shape risk.

According to the research team's leader, Hakon Hakonarson, "We focused on changes in the exons of DNA--protein-coding areas in which deletions or duplications are more likely to directly disrupt biological functions. We identified additional autism susceptibility genes, many of which belong to the neuronal cell adhesion molecule family involved in the development of brain circuitry in early childhood."

This research, if confirmed, supports the notion that autism spectrum disorder is a heterogeneous group of disorders, with a heterogeneous set of causes some (or most?) of which may be genetic.

Bucan, M., Abrahams, B., Wang, K., Glessner, J., Herman, E., Sonnenblick, L., Alvarez Retuerto, A., Imielinski, M., Hadley, D., Bradfield, J., Kim, C., Gidaya, N., Lindquist, I., Hutman, T., Sigman, M., Kustanovich, V., Lajonchere, C., Singleton, A., Kim, J., Wassink, T., McMahon, W., Owley, T., Sweeney, J., Coon, H., Nurnberger, J., Li, M., Cantor, R., Minshew, N., Sutcliffe, J., Cook, E., Dawson, G., Buxbaum, J., Grant, S., Schellenberg, G., Geschwind, D., & Hakonarson, H. (2009). Genome-Wide Analyses of Exonic Copy Number Variants in a Family-Based Study Point to Novel Autism Susceptibility Genes PLoS Genetics, 5 (6) DOI: 10.1371/journal.pgen.1000536


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An incredible study with massive implications for the future of autism. Too bad it is overshadowed by the death of a washed up pop star.

By Jay Kanta (not verified) on 26 Jun 2009 #permalink

Did they really have to refer to the controls as 'disease-free'?

By Lucas McCarty (not verified) on 26 Jun 2009 #permalink

I've been waiting for this for a while! Not that this will shut up Jim and Jenny but still. Evidence-based science for the win!

Lucas: agreed, I thought autism was considered a "condition", not a "disease". But I've also been told I'm too much a stickler for word meanings.

Sorry to be down on this study, but most of the individuals with the copy number variants didnât have autism. If you look at supplement table 2, among the deletions and duplications there were more unaffected family members with the CNVs than people with autism.

There were only 5 CNVs (out of 361) that had zero unaffected carriers.

A smoking gun for autism, this isnât.

Did they really have to refer to the controls as 'disease-free'?

Of course they did. There was a recent study that indicated that people with ASDs are less prone to having their decisions affected by manipulative emotional appeals; the mental gymnastics that many of those reporting on the study went through in order to characterize this as a "deficiency" were practically olympic material.

Luna the cat: Thanks for the linked article! This looks very, very significant. If it's (eventually) possible to use their findings as a basis for a treatment--rather than just a marker for genetic screening--this could be a huge breakthrough in improving the lives of children with autism. High-functioning autism can be viewed as a difference rather than a disorder, but the kids with severe autism don't seem to enjoy their lives.