Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder

The DNA of protein-coding genes is transcribed into mRNA, which is translated into proteins. The "coding genome" describes the DNA that contains the information to make these proteins and represents 1.5% of the human genome. Newly arising de novo mutations (variants observed in a child but not in either parent) in the coding genome contribute to numerous childhood developmental disorders, including autism spectrum disorder (ASD). Discovery of these effects is aided by the triplet code that enables the functional impact of many mutations to be readily deciphered. In contrast, the "noncoding genome" covers the remaining 98.5% and includes elements that regulate when, where, and to what degree protein-coding genes are transcribed. Understanding this noncoding sequence could provide insights into human disorders and refined control of emerging genetic therapies. Yet little is known about the role of mutations in noncoding regions, including whether they contribute to childhood developmental disorders, which noncoding elements are most vulnerable to disruption, and the manner in which information is encoded in the noncoding genome. Whole-genome sequencing (WGS) provides the opportunity to identify the majority of genetic variation in each individual.