Evan Eichler and Robert Darnell provide deep whole genome sequencing of 516 families with idiopathic autism, providing insights into the complex etiology of simplex autism.
Although mutations — the fundamental process by which genomic variation is acquired — are necessary to the evolution and success of a species, they are also the origin of all genetic disease. Hence, defining the mechanisms that control their occurrence is crucial to our basic understanding of genome biology, disease mechanisms and, ultimately, evolution.
Dysregulation of the intracellular signaling pathway RAS, a risk factor for idiopathic autism, may provide a unifying theory of the disorder. Although this is not an altogether new hypothesis, several new findings have strengthened the evidence for it considerably.
Advanced maternal and paternal age have been reported as risk factors for autism spectrum disorders. In general, the genetic quality of eggs and sperm declines over time, reducing the chance of older parents to produce normal offspring. Copy-number variation (CNV) — a type of genetic alteration commonly associated with autism spectrum disorder — is thought to be one of the most common problems with the quality of eggs or sperm in older individuals.
To explore the genetic contribution in autism spectrum disorders, Michael Wigler and his colleagues at Cold Spring Harbor Laboratory in New York studied genomic variation in the Simons Simplex Collection (SSC), a large cohort of families that have one child with autism and unaffected parents and siblings.