Researchers at Hopkins who are leading an international team have identified genes that may contribute to autism. Prior to these findings, attempts at linking specific genes with autism have had limited success, even though some studies suggest that the disorder may be inheritable.
The findings were made through a collaboration called the Gene Discovery Project between Hopkins and the Autism Consortium, and involved Aravinda Chakravarti and Dan Arking of Hopkins's McKusick-Nathans Institute of Genetic Medecine, Mark Daly and Lauren Weiss of the Center for Human Genetic Research at Massachusetts General Hospital and the Broad Institute of MIT and Harvard.
The study analyzed samples of half a million genome markers, or single nucleotide polymorphisms (SNPs) from the Autism Genetic Resource Exchange, the Autism Consortium in Montreal, the Autism Genome Project and the U.S. National Institute of Mental Health.
"We were greatly helped in our research by having family samples from numerous autism support organizations," Chakravarti said. Chakravarti is a professor of medicine, pediatrics, molecular biology and genetics at the NcKusick-Nathans Institute of Genetic Medicine at Hopkins. Samples also came from Finland and Iran.
Although the technology available to analyze large amounts of data from thousands of human genomes has improved significantly, even compared to five years ago, there are still limits.
"[The] powerful technologies that we, as a member of the human genetics community, developed are now finding routine use, but it is frustrating that these technologies have not yet higher resolution," Chakravarti said.
The team read the genomes of family members of individuals diagnosed with a form of autism and studied 1,031 nuclear families and 1,553 autistic children in all. Through meta-analysis, it was found that the semaphorin 5A protein is significantly less present in autism brains than in non-autism brains.
The study also found evidence to suggest that genetic variants are linked to autism. This finding was achieved through two types of analysis. Firstly, examining areas of the human genome of siblings with autism revealed that four chromosomes ?- 6, 15, 17 and 20 - had rare variants from non-autism samples.
Moreover, when this analysis was combined with samples of unrelated people with autism, the researchers found that semaphorin 5A, which controls nervous system connections made in the brain through its protein product, was where the only common variation occurred.
Dan Arking, assistant professor of medicine at Hopkins' McKusick-Nathans Institute of Genetic Medicine, acknowledges that other genes affect the condition. "There probably are many more [genes] that contribute to autism, but none have large effects," Arking said.
Arking added that another possibility is that there are numerous rare gene-variant containing genes, studies of which are ongoing. There are seven additional candidates of genes likely to be similarly involved in the development of the nervous system, but their influence has not yet been proven.
"[The study] contributes to our fundamental understanding of autism and as of yet, not to questions of diagnosis or therapy," Chakravati said.
Mark Daly, a senior associate member of the Broad Institute of Harvard and MIT and an associate professor at the Center for Human Genetic Research at Massachusetts, believes that areas of further research have been opened up by the results of this study.
"The genomic regions we've identified help shed additional light on the biology of autism and point to areas that should be prioritized for further study," Daly said. Their research was made possible by the National Institute of Mental Health and the Simons Foundation.
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