For their initial studies, the researchers examined roughly half a million genetic markers in more than 1,000 families from the Autism Genetic Resource Exchange (AGRE) and the US National Institute of Mental Health (NIMH) repositories. Follow-up analyses were conducted in collaboration with the Autism Genome Project as well as other international groups. "We are deeply grateful to all of the patients and their families who made this work possible," said Daly.

The researchers' results highlight three regions of the human genome. These include parts of chromosomes 6 and 20, the top-scoring regions to emerge from the family-based linkage studies. Although further research is needed localize the exact causal changes and genes within these regions that contribute to autism, these findings can help guide future work.

The other major result, this one flowing from the population-based analyses, is a single-letter change in the genetic code known as a single nucleotide polymorphism, or SNP (pronounced "snip"). This common variant lies on chromosome 5 near a gene known as semaphorin 5A, which is thought to help guide the growth of neurons and their long projections called axons. Notably, the activity or "expression" of this gene appears to be reduced in the brains of autism patients compared to those without the disorder.

"These genetic findings give us important new leads to understand what's different in the developing autistic brain compared with typical neurodevelopment. We can now begin to explore the pathways in which this novel gene acts, expanding our knowledge of autism's biology," said co-lead author Lauren Weiss, a former postdoctoral fellow who collaborated with Daly and his colleagues at MGH and the Broad Institute. Weiss is now an assistant professor of psychiatry and human genetics at University of California, San Francisco (UCSF).

Although the Nature paper identifies a handful of new genes and genomic regions, the researchers emphasize that the findings are just one piece of a very large - and mostly unfinished - puzzle. Future studies involving larger patient cohorts and higher resolution genomic technologies, such as next-generation DNA sequencing, promise to yield a deeper understanding of autism and its complex genetic roots.

Source: Broad Institute of MIT and Harvard