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Stimulus grant to fund whole-genome sequencing in children with autism
Date:9/30/2009

hnology and informatics techniques that should help to understand many kids with autism," Walsh says.

The team will begin by analyzing the "exome" the 2 percent of the genome that directly codes for proteins. For patients whose genetic cause remains a mystery, a second phase of the study will sequence and analyze the entire genome's 3.2 billion base pairs (combinations of A, C, T and G) that make up our full complement of 20,000 to 25,000 genes. In this way, the researchers hope to discover noncoding portions of the genome -- sometimes called "junk" DNA -- that don't make proteins but may contain critical switches that control gene activity.

The informatics part of the project, led by Timothy Yu, MD, PhD, in the Walsh Lab, will be the most important and challenging. With new machines, DNA sequencing has become relatively easy and cheap; what's hard is interpreting the flood of information. The researchers will compare sequence information from their autism patients with that from normal controls, using data from the international "1000 Genomes Project," allowing them to distinguish normal person-to-person genetic variations from variations that cause autism. "These new data should give us enormous power to interpret the findings in our autism patients, and figure out what's the signal and what's noise," Walsh says. "Three million letters in the DNA sequence may differ between you and me -- we need to figure out which changes are causing the disease."

A separate part of the project, led by Greenberg, will look at gene activity in human neurons, focusing on genes that lie in chunks of DNA that were previously found to be deleted in the Middle Eastern families with autism. In 2008, Greenberg and Walsh reported that some autism mutations may affect "promoter" or "enhancer" sequences, bits of DNA that act as "on/off" switches controlling gene activity. (See: http://www.childrenshospital.org/newsroom/Site1339/mainpageS1339P1sublevel445.html.)
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Contact: Jamie Newton
james.newton@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

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