Project Summary

Louis Kunkel, Ph.D. (Distinguished Investigator 2007) of the Children’s Hospital of Boston, plans with NARSAD support to leverage work from his involvement in an Autism Collaborative, a multidisciplinary research team at his institution that is part of the multi-institutional Boston-based Autism Consortium, to study gene expression in autistic children. Dr. Kunkel has had a long interest in the genetics of human disease, with early work concentrating on the genetics of muscular dystrophy, positional cloning of the dystrophin gene and the documentation of causative mutations in patients with Duchene Muscular Dystrophy. This research led to improved diagnosis of the muscular dystrophies and the design of rational therapies. He has now studying autism spectrum disorders. Working with the director of the Bioinformatics Program at Children's Hospital, he has initiated a large-scale study of gene expression in autistic children, their surrounding family members and unrelated controls. They have found large numbers of genes expressed in tissues in which they were not thought to function, including many expressed in the brain. Dr. Kunkel hypothesizes there is a strong possibility that autism may not be caused by a common genetic polymorphism/variation in each of a group of genes which leads to the autistic phenotype, but more likely by multiple, different rare variants in these same genes. These rare variants would not be detected by case control studies with tagging single nucleotide polymorphisms. They can only be found by deep re-sequencing of multiple candidate genes in hundreds of autism patients and controls. They have developed several techniques to prioritize and focus those areas of the genome that are most likely to be revealing in their re-sequencing efforts.

Program Area: PERVASIVE DEVELOPMENTAL DISORDERS\Autism

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