Frequency and Complexity of De Novo Structural Mutation in Autism.

TitleFrequency and Complexity of De Novo Structural Mutation in Autism.
Publication TypeJournal Article
Year of Publication2016
AuthorsBrandler WM, Antaki D, Gujral M, Noor A, Rosanio G, Chapman TR, Barrera DJ, Lin GNing, Malhotra D, Watts AC, Wong LC, Estabillo JA, Gadomski TE, Hong O, Fajardo KVFuentes, Bhandari A, Owen R, Baughn M, Yuan J, Solomon T, Moyzis AG, Maile MS, Sanders SJ, Reiner GE, Vaux KK, Strom CM, Zhang K, Muotri AR, Akshoomoff N, Leal SM, Pierce K, Courchesne E, Iakoucheva LM, Corsello C, Sebat J
JournalAm J Hum Genet
Date Published2016 Apr 7

Genetic studies of autism spectrum disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment of structural variants (SVs) has been restricted by the coarse resolution of current approaches. By applying a custom pipeline for SV discovery, genotyping, and de novo assembly to genome sequencing of 235 subjects (71 affected individuals, 26 healthy siblings, and their parents), we compiled an atlas of 29,719 SV loci (5,213/genome), comprising 11 different classes. We found a high diversity of de novo mutations, the majority of which were undetectable by previous methods. In addition, we observed complex mutation clusters where combinations of de novo SVs, nucleotide substitutions, and indels occurred as a single event. We estimate a high rate of structural mutation in humans (20%) and propose that genetic risk for ASD is attributable to an elevated frequency of gene-disrupting de novo SVs, but not an elevated rate of genome rearrangement.

PubMed URL
Alternate TitleAm. J. Hum. Genet.
PubMed ID27018473
PubMed Central IDPMC4833290
Grant ListR01 HD065288 / HD / NICHD NIH HHS / United States
R01 MH105524 / MH / NIMH NIH HHS / United States
R21 MH104766 / MH / NIMH NIH HHS / United States
Bioinformatics and Systems Biology