24 new autism-related gene variants identified
In a new study, researchers have extended out understanding of genes related to autism spectrum diseases (ASDs) and advances methods for early detection and treatment.
Nori Matsunami, one of the three lead authors from the University of Utah (the U), contributed equally to the paper and worked with Mark Leppert.
With colleagues from the Children's Hospital of Philadelphia (CHOP), Lineagen Inc. (Salt Lake City) and Golden Helix Inc. (Bozeman, Mont.), the study identifies 24 new copy number variants (CNVs) and #65533; missing or duplicated stretches of DNA and #65533; with a strong link to autism.
"Utah has long been leading the way in disease-relevant genetic discoveries," Leppert said.
"The newly identified variants were discovered based on CNVs and gene sequence variants originally found in multigenerational Utah ASD families. The ability to replicate the association in a second, large ASD population is a major step forward in understanding the genetic markers associated with ASD," he said.
Startup company Lineagen, Inc., which launched in 2002 based on U technology, is providing a related test for ASD diagnosis.
The study validates the genetic markers used in this test. The product, called FirstStepDx PLUS, tests for many ASD markers, including the 24 new ones discovered. Dr. Leppert is a scientific advisor to Lineagen.
Highlights of the study include use of familial cases, molecular validation of identified CNVs and replication in the largest ASD study of its kind, immediate clinical utility of results due to large sample size, confirms some previously published CNVs, new and previously known markers could provide genetic diagnosis for up to 10-12 percent of children with ASD, and identification of potential biochemical pathways that pharmaceutical companies could use for ASD drug development targets.
This long-term study began with U researchers identifying 55 people from Utah families with multiple members diagnosed with ASDs. From there, they identified 153 CNVs with a potential link to autism.
Building on findings at the U, researchers at CHOP, led by Hakon Hakonarson, M.D., Ph.D., and the U team designed a custom DNA microarray chip to detect CNVs.
They analyzed a population of 3,000 people with ASD and a control group of 6,000, and identified 24 CNVs with an odds ratio of greater than 2.0. That means people with those CNVs are twice as likely to have an ASD compared to a member of the control group.
"Many of these gene variants may serve as valuable predictive markers," Hakonarson said.
"If so, they may become part of a clinical test that will help evaluate whether a child has an autism spectrum disorder," Hakonarson added.
The study has been published online in PLOS ONE.