TY - JOUR T1 - Frequency and complexity of de novo structural mutation in autism JF - bioRxiv DO - 10.1101/030270 SP - 030270 AU - William M Brandler AU - Danny Antaki AU - Madhusudan Gujral AU - Amina Noor AU - Gabriel Rosanio AU - Timothy R Chapman AU - Daniel J Barrera AU - Guan Ning Lin AU - Dheeraj Malhotra AU - Amanda C Watts AU - Lawrence C Wong AU - Jasper A Estabillo AU - Therese E Gadomski AU - Oanh Hong AU - Karin V Fuentes Fajardo AU - Abhishek Bhandari AU - Renius Owen AU - Michael Baughn AU - Jeffrey Yuan AU - Terry Solomon AU - Alexandra G Moyzis AU - Stephan J Sanders AU - Gail E Reiner AU - Keith K Vaux AU - Charles M Strom AU - Kang Zhang AU - Alysson R Muotri AU - Natacha Akshoomoff AU - Suzanne M Leal AU - Karen Pierce AU - Eric Courchesne AU - Lilia M Iakoucheva AU - Christina Corsello AU - Jonathan Sebat Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/10/30/030270.abstract N2 - Genetic studies of Autism Spectrum Disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment of structural variation (SV) 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 cases, 26 sibling controls and their parents, we present an atlas of 1.2 million SVs (5,213/genome), comprising 11 different classes. We demonstrate a high diversity of de novo mutations, a majority of which were undetectable by previous methods. In addition, we observe 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%). Genetic risk for ASD is attributable to an elevated frequency of gene-disrupting de novo SVs but not an elevated rate of genome rearrangement. ER -