A Firm Foothold in the Genetics of Autism

Matthew State had never seriously considered a career in genetic research until 1995, when he spent a few months in a child psychiatry ward during his residency at the University of California, Los Angeles. There he cared for a few children with Prader-Willi syndrome, a rare genetic disorder caused when all or part of a seven-gene stretch of chromosome 15 is missing. Children with Prader-Willi tend to be intellectually delayed and prone to compulsive behaviors such as skin-picking and uncontrollable eating.“These kids just had one region lost, but it led to a variety of psychiatric manifestations,” State recalls. “It made me start thinking, quite naively, about studying rare mutations as a way of understanding disorders that are much more common in the population.” The notion led State, at age 35, to enroll in the graduate program in genetics at Yale, where others were thinking along the same lines. Most famously, faculty member Richard Lifton, now chair and Sterling Professor of Genetics, had discovered a trove of new genes involved in hypertension by screening families with rare, extreme blood pressure disorders.In recent years, State, now co-director of the Yale Program on Neurogenetics at the School of Medicine, has been employing the latest genomic technologies to take the same general approach to the notoriously diverse autism spectrum disorders. Studies have found dozens of genetic blips in people with autism, which is characterized by repetitive behaviors and problems in communication and social interactions, but researchers have struggled to sort out which of these gene variants are harmful and which benign.State and several other groups around the country have attacked this problem by focusing on an unusual group of study participants known as the Simons Simplex Collection (SSC). Assembled and maintained with funding from the New York City-based Simons Foundation, the SSC includes blood samples and extensive medical information from 2,700 families in which one child has been diagnosed with autism. The families are recruited from 13 clinics across the country, each using the same precise measures to confirm autism diagnoses. Researchers collect blood samples from not only the children with autism, but from parents and unaffected siblings. The term “simplex” in the SSC’s name refers to the fact that the collection includes only families with a single child with autism and at least one unaffected child, making it easier to draw precise genetic comparisons between affected and unaffected family members.Read more at...Medicine@Yale, May 2012.