Researchers at the University of California San Diego announced on Mar. 9 that they have identified new genetic variants associated with autism spectrum disorder by using long-read whole genome sequencing, a method that reads large sections of the genome at once. This approach makes it easier for scientists to find new genetic variants and understand how these variants affect gene function.
The study is significant because, despite advances in understanding autism genetics, much of its genetic basis remains unexplained—a challenge known as "missing heritability." The researchers said their work demonstrates that long-read sequencing can uncover gene mutations previously undetectable with traditional short-read technologies. This research is among the first large-scale studies of autism to use this advanced sequencing technique.
By analyzing 267 genomes from families affected by autism, the team found that long-read sequencing improved the discovery of several categories of genetic variants compared to older methods. The findings could lead to more accurate genetic tests and may enable therapies targeting specific genetic mechanisms underlying autism spectrum disorder.
The researchers noted that while this is the largest study of its kind so far, even larger analyses will be needed to determine exactly how much missing heritability can be explained using long reads. Study author Sebat said he believes this technology could double the amount of heritability explained by certain types of variants, such as tandem repeats and structural changes in DNA.
The study was published in Cell Genomics and received funding from grants provided by the National Institute for Mental Health, the National Institute of Drug Abuse, and the National Human Genome Research Institute.
As research continues, scientists hope that expanding these studies will further clarify autism's complex genetic origins and support development of targeted interventions.
