Autism Research - Hopkins Team Comments on CNTNAP2 Gene Autism Study

The John Hopkins research study, one of three reported in the January 2008 issue of the American Journal of Human Genetics that confirmed the CNTNAP2 gene as an important genetic link to autism susceptibility, is commented on by some of the study's lead researchers in Hopkins Team Identifies Autism Susceptibility Gene. Aravinda Chakravarti, Ph.D., professor of medicine, pediatrics and molecular biology and genetics and member of the McKusick-Nathans Institute of Genetic Medicine at Hopkins and Dan Arking Ph.D., an assistant professor at the McKusick-Nathans Institute explain the methodology the followed in the study and some interesting findings. Some interesting findings in the study - that autistic individuals are more likely to get the T allele, a key genetic variant associated with autism, from mothers than fathers, and more likely to be boys than girls.

Using genome-wide analysis, the team first analyzed DNA from 292 individuals, including 148 affected offspring. They compared single nucleotide polymorphisms, or SNPs, the differences in single chemical’s building blocks of the DNA at the same point across many people. They found that autistic individuals tend to inherit the DNA letter T from their parents much more often than expected by chance at one particular place on the chromosome.

To validate their finding, the team then repeated their approach with a separate group of samples consisting of 1,295 parent-child trios. They again found an over representation of T, confirming that inheritance of the T genetic variant is associated with increased risk of developing autism.

The T genetic variant is found in the middle of the CNTNAP2 gene, short for contactin-associated protein-like 2, which codes for a protein that’s thought to mediate cell communication in the nervous system.

The researchers then looked at the same data to see if there were differences in which parent the T allele is inherited from and the gender of the child. They found that autistic individuals are more likely to get the T allele from mothers than fathers, and more likely to be boys than girls.

“We know that boys are four times as likely as girls to be autistic,” says Chakravarti. “And now we have some intriguing evidence suggesting that the gene may show a parent-of-origin effect.”

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