Researchers identify autism-causing genetic mutations

Dr. Mazhar Adli, assistant professor of Biochemistry and Molecular Genetics, contributed to a study published last month in the scientific journal Neuron. The study, led by Harvard Medical School Prof. Christopher Walsh, outlines a method for identifying familial genetic mutations which contribute to the partial loss of gene function common in autism spectrum disorders.

The project used whole-exome sequencing, a process which cuts out and studies small portions of DNA called exons that code for functional proteins. Using this process researchers located regions of the genome that could be affected by the genetic variants associated with autism disorders, Adli said. According to the study, there are some rare alleles — variations of genes that code for certain traits — in genomes that contribute to the development of autism. In this study, researchers combined whole-exome sequencing and biochemical assays to pinpoint these variants and test whether they are the cause of autism spectrum disorders. For a particular sequence to be identified as contributing to the disease, it must cause a structural change in the protein it codes for.

“[Our] research differs from a lot of other genomic approaches,” Adli said. “It’s not just reported that Gene X is mutated or Gene Y is mutated; it is also testing that these mutations are actually causing the disease.”

This research confirms the complexity of the genetic architecture of autism, identifying a number of variants that contribute to the disease, but Adli said there is still a lot of work to do. “Currently, researchers are not aware of what 98 percent of the genome does,” Adli said. “We are only really beginning to understand the epigenome.”

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