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News

Geneticist ues rsequencing tchnology to sudy Autism Susceptibility Genes

Emory University : 10 February, 2007  (Technical Article)
The recent sequencing of a single human genome was the first step in speeding the discovery of genetic variations that contribute to disease in humans. Now a geneticist is using microarry-based 'resequencing', new technology he helped develop,to search for genes on targeted sections of the X chromosome that could be related to the development of autism.
The recent sequencing of a single human genome was the first step in speeding the discovery of genetic variations that contribute to disease in humans. Now a geneticist is using microarry-based 'resequencing', new technology he helped develop,to search for genes on targeted sections of the X chromosome that could be related to the development of autism.

Michael Zwick, PhD, assistant professor of Human Genetics at Emory University School of Medicine, has received a five-year grant totaling approximately $1.3 million from a public/private partnership of government health agencies and private advocacy organizations, including five institutes within the National Institutes of Health, Cure Autism Now, the National Alliance for Autism Research, and the Southwest Autism Research and Resource Center. The Emory grant is one of five grants awarded nationally for genetic autism research.

Autism has an incidence rate of 1 in every 166 children. Symptoms include varying degrees of impairment in communication and social skills and repetitive patterns of behavior. Strong evidence from twin and family studies indicates that at least some cases of autism are inherited; however, no single gene has been found to explain autism, and scientists now believe genetic susceptibility may be caused by multiple genes, along with environmental factors.

Dr. Zwick helped develop the microarray resequencing technology first as a post-doctoral fellow at Johns Hopkins, and then as a Navy reservist working at the Naval Medical Research Center in Silver Spring, Md. Microarray, or DNA chip resequencing, allows scientists to determine 300,000 base pairs of an individual's genome (the G, A, T, C in the DNA sequence) using square chips that are just .75 inches long by .75 inches wide. This allows scientists to examine specific chromosomal regions in large collections of human patients to uncover subtle variations that could have significant consequences for health and disease.

Whereas the more well-known microarray gene chips are designed to detect differences in gene expression by measuring changes in RNA, resequencing chips aim to identify genetic variation in the DNA sequence itself within a selected region of the genome, based on a reference sequence of 'normal' DNA. The resulting data is similar to that produced by a large DNA sequencing center, but uses a technology accessible by an individual scientist. Until now, if a scientist wanted to sequence 300,000 base pairs of DNA, he or she would have to use a more time-consuming PCR technology with conventional sequencing chemistries, focusing on just 500 base pairs at once.

'Resequencing chips allow a single laboratory to generate a great deal of genetic data from many individuals at a cost significantly less than what a genome sequencing center would charge,' says Dr. Zwick.

His laboratory will use resequencing chips to search for autism susceptibility genes on the X chromosome. The incidence of autism is four times higher in males than in females, suggesting a possible sex-linked gene or genes. The Emory scientists will look especially closely at the FMR1 gene, which is responsible for fragile X syndrome, the most common cause of inherited mental retardation. Approximately 20 percent of patients diagnosed with fragile X also meet diagnostic criteria for autism and often are misdiagnosed with autism. Dr. Zwick hopes his discoveries will yield insight into genetic variations responsible for the autism susceptibility shared by both disorders.
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