Researchers at Cold Spring Harbor Laboratory (CSHL) recently broke down the generally accepted genetic assumptions For years, scientists believed that siblings diagnosed with ASD tended to inherit more genetic traits from their mothers than from their fathers. However, CSHL Associate Professor Ivan Iossifov and Professor Michael Wigler have shown that in many cases it may often be the father who makes a greater genetic contribution.
Autism spectrum disorders cover a range of neurological and developmental disorders. They can affect how a person communicates, socializes, learns and behaves. ASD can also manifest as repetitive behavior or restricted interests. In the United States, it affects about one in 36 children.
“There are children diagnosed with autism who function well,” Iossifov says. “They have perfectly productive lives, although they have some minor difficulties in social interactions, like most of us. But there are also children diagnosed with autism who never learn to speak, and they definitely have a difficult life.”
Over the past two decades, CSHL scientists have spent millions of dollars trying to uncover the genetic origins of autism. They discovered thousands of genes that, when damaged, can cause a child to be born with ASD. But their work could not explain all cases of ASD. So Iossifov and Wigler set out to find the missing sources.
The duo analyzed the genomes of more than 6,000 volunteer families. They found that in families with two or more children with ASD, the siblings shared more of their father’s genome. Meanwhile, in families where only one sibling had ASD, the children shared less of their father’s genome. While the discovery reveals a new potential source of ASD, it also raises a provocative question. Could other conditions play by the same genetic rules?
No one knows for sure how father’s genome makes its mark on children with ASD. But Iossifov has some interesting ideas. He thinks some fathers carry protective mutations that aren’t passed on. Or fathers can pass on mutations that trigger the mother’s immune system to attack the developing embryo. Both theories offer hope for parents of children with ASD and other neurological disorders such as schizophrenia.
“Our future research is exciting,” says Iossifov. “If one or two of those theories turn out to be true, then it opens up different treatment strategies, which could affect a lot of families in the future.”
In addition, this research offers useful tools for educators and therapists. It can provide earlier diagnoses and a better overall understanding of autism.
Reference: “Sibling Parental Genome Sharing Concordant or Discordant for Autism” By Mathew Wroten, Seungtai Yoon, Peter Andrews, Boris Yamrom, Michael Ronemus, Andreas Buja, Abba M. Krieger, Dan Levy, Kenny Ye, Michael Wigler and Ivan Iossifov, May 8, 2023, Cell genomics.
The study was funded by the Simons Center for Quantitative Biology, the Simons Foundation Autism Research Initiative, the Centers for Common Disease Genomics, the National Human Genome Research Institute and the National Heart, Lung and Blood Institute.