Rare Genetic Variant Linked to Autism, YSPH Study Finds

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Scientists at the Yale Center for Perinatal, Pediatric and Environmental Epidemiology have established that a rare genetic variant accounts for approximately 1 percent of the incidence of autism. The work is described in an upcoming paper which combined data from seven previous studies of patients with an autism spectrum disorder (ASD).

Autism is one of the most heritable complex disorders, but numerous studies have had little success in determining the underlying genetic causes of the condition. Recently, several rare deletions and duplications of chromosomal regions, known as copy-number variants, have been shown to contribute to autism incidence. Most individuals have two copies of each gene, one inherited from their mother and the other from their father. Individuals with copy-number variants have either too many or too few copies of a gene. Depending on which genes are affected, copy-number variants can be either benign or disease-causing mutations. Several neuro-developmental disorders are caused by specific copy-number variants, including Williams syndrome, Smith-Magenis syndrome and Prader-Willi syndrome.

Variants in a specific region on Chromosome 16 have repeatedly been linked to autism, but individual studies found copy-number variants in only a small proportion of the patients under study. To estimate what proportion of all ASDs may be attributable to this variant, the Yale researchers sought to determine what proportion of autistic individuals carry this copy-number variant. Combining genetic data from 3,613 autistic patients using a technique known as meta-analysis, the researchers determined that 0.76 percent of all ASDs may be caused by duplication or deletion of this region of Chromosome 16.

“Combined with other copy-number variants which also have strong associations with autism, genomewide scans for gene deletions/duplication are expected to become part of routine clinical practice when caring for autistic patients,” said Kyle M. Walsh, a Ph.D. candidate at the Yale School of Public Health and the study’s lead author.

The copy-number variable region on Chromosome 16 contains 25 known genes. Further research is needed to determine which gene, or combination of genes, contributes to the development of autism. Because both duplications and deletions in the region are associated with autism, it appears that the region is very sensitive to departures from the normal two-copy state. Data presented in the paper is expected to be valuable to clinicians working in the field of medical genetics and genetic counseling. Results indicate that approximately 132 autistic patients need to be tested to identify one individual who carries a variant in this region of Chromosome 16. 


The paper will appear in the May issue of Genetics in Medicine. Michael B. Bracken, Susan Dwight Bliss Professor of Epidemiology and co-director of the Yale Center for Perinatal, Pediatric and Environmental Epidemiology, is the paper’s senior author.


This Article was submitted by Denise Laraine Meyer, on Thursday, June 28, 2012.