Older Men at Increased Risk for Fathering Children with Autism

It has been known for a long time, that women over 30 years of age are at increasing risk for giving birth to children with certain developmental disorders, such as Down Syndrome. In an article just published in Translational Psychiatry (2011) 1, e34; doi:10.1038/tp.2011.30 published online 30 August 2011, examined the basis for the repeated finding that children of older fathers have an increased risk of neurodevelopmental disorders. Several previous studies that have shown the children of older fathers have an increase
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d risk of a range of neuropsychiatric disorders, including autism, schizophrenia, bipolar disorder and epilepsy. The mechanisms underlying the increased risk of various neurodevelopmental disorders in the offspring of older fathers remain unclear; however, it has been proposed that copy number variants (CNVs) in the continually dividing sperm cells in older men underlie this association. Copy-number variations (CNVs)—a form of structural variation—are alterations of the DNA of a genome that results in the cell having an abnormal number of copies of one or more sections of the DNA.

In the present study, the researchers used genes in a mouse model of human chromosomes and applied genome-wide screening technology. They studied genes in older male mice and their offspring and found two of the genes in the offspring were associated with behavioral and/or neuroanatomical characteristics. One of the genes involved Auts2 (autism susceptibility candidate 2), and others included genes linked to schizophrenia, autism and brain development. This is the first experimental demonstration that the offspring of older males have an increased risk of genetic errors related to autism. Their results support the hypothesis that the offspring of older fathers have an increased risk of neurodevelopmental disorders such as schizophrenia and autism by spontaneously producing abnormal copy numbers in male sperm cells. Just how old is old, isn’t entirely clear yet. [email protected]