The Simons Foundation has awarded scientists at Emory University School of Medicine a three-year grant of more than $3 million to uncover genes on the X chromosome that may contribute to the development of autism.
Stephen T. Warren, PhD, chair of the Emory Department of Human Genetics, is principal investigator of the program project that also includes Michael Zwick, PhD, and Brad Coffee, PhD, both Emory faculty members in human genetics.
Autism occurs four to nine times more frequently in males than in females, and genes on the X chromosome have long been suspected as being responsible for this male predilection. However, the ability to comprehensively examine the entire X chromosome for abnormalities has not been technically feasible until now.
Using technologies recently developed in the Department of Human Genetics, the Emory scientists will carry out a comprehensive search for genetic abnormalities of the X chromosome in 330 patients with autism.
The first project will scan the entire length of the X chromosome for subtle deletions or duplications using high-resolution microarrays containing short DNA fragments that can interrogate 2.1 million sites on the X chromosome. The second project will sequence all of the 1,098 genes on the X chromosome using a “next generation” DNA sequencing instrument. The final project will scan the entire X chromosome for evidence of “epigenetic” abnormalities, which are due to differences in gene expression rather than changes in the DNA itself.
This exhaustive survey of the human X chromosome should identify X-linked variation for autism susceptibility if such variation exists, says Dr. Warren.
“The unique genomic technologies available at Emory allow studies that would have been incomprehensible only a few years ago and will enable us to examine the 155 million bases of the X chromosome in minute detail in patients with autism,” he explains.
Finding a predisposing gene is considered the most important first step to uncovering the true basis of a disease and to developing diagnostic tests and therapeutic approaches.