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Researchers Identify 24 More “High Impact” Autism Gene Changes

January 14, 2013

Genetic researchers have discovered another 24 “high impact” autism gene changes. Each more than doubles the risk that a child will develop autism.

The discoveries bring doctors closer to a practical gene test that can help diagnose autism or identify young children as being at-risk before symptoms appear. Such testing could help identify infants and toddlers who could benefit from early interventions that promote healthy brain development and improve outcomes.

"These high-impact variants could be most useful in advising parents who have one child with an ASD and a younger child with delays in reaching developmental milestones," says senior author Hakon Hakonarson, M.D., Ph.D. Dr. Hakonarson directs the Center for Applied Genomics at the Children’s Hospital of Philadelphia. The hospital is a member of Autism Speaks Autism Treatment Network (ATN).

The study appears this week in the open-access journal PLOS One. It used DNA samples from participants at the Children’s Hospital of Philadelphia as well as Autism Speaks Autism Genetic Resource Exchange (AGRE). AGRE is the world’s largest private repository of genetic and clinical information from families with more than one member affected by autism. Dr. Hakonarson also collaborated with scientists from the University of Utah and the biotechnology company Lineagen.

Current gene tests can identify known autism risk genes in less than 20 percent of those with autism spectrum disorder (ASD). Yet some degree of genetic predisposition is thought to be involved in most if not all cases.

In recent years, the emergence of micro-array DNA technology has dramatically advanced the search for autism’s missing genetic factors. Using this technology, researchers have associated autism with hundreds of gene changes called copy number variants (CNVs). CNVs consist of duplications or deletions of entire sections of DNA. Individually, any one CNV is rare. But as a group, they are relatively common – particularly among individuals with autism.

In the new study, the researchers analyzed DNA from 55 individuals in families that had more than one member affected by autism. In doing so, they identified 153 new CNVs associated with increased autism risk.

Next they sought to identify which of these CNVs had a “high impact.” They defined “high impact” as more than doubling autism risk.

They created a DNA microarray with probes for the 153 newly discovered CNVs as well as 185 CNVs previously associated with autism. They then used the array to analyze 3,000 DNA samples, two-thirds of which came from the AGRE database. The balance came from participants at the Children’s Hospital of Philadelphia, as did comparison DNA samples from 6,000 persons without autism.

In all, the study identified 55 high-impact autism gene changes. These included 24 newly discovered autism CNVs and 31 previously identified CNVs. All the variations involved genes that influence the development of nerve cells and brain signaling pathways.

“Many of these gene pathways active in ASDs overlap with those in other nervous system disorders, such as schizophrenia and epilepsy," Dr. Hakonarson says. The results are also consistent with other studies suggesting that many biological pathways, when disrupted, can lead to ASDs, he added.

“Autism Speaks is gratified to see its scientific resources used to enable discoveries with the potential to directly benefit our families,” says Clara Lajonchere, Ph.D. Dr. Lajonchere oversees the AGRE database and consortium as Autism Speaks vice president for clinical programs. “If confirmed, these findings bring us closer to gene tests that can improve autism diagnosis,” she says. “They also have the potential to allow us to identify autism subtypes most likely to respond to particular therapies.”

Autism Speaks continues to fund a wealth of research on the causes, early diagnosis and treatment of autism. You can explore these studies using this website’s Grant Search. For more information on CNVs and autism, see these related news stories.