RT Journal Article
SR Electronic
T1 Frequency and complexity of de novo structural mutation in autism
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 030270
DO 10.1101/030270
A1 William M Brandler
A1 Danny Antaki
A1 Madhusudan Gujral
A1 Amina Noor
A1 Gabriel Rosanio
A1 Timothy R Chapman
A1 Daniel J Barrera
A1 Guan Ning Lin
A1 Dheeraj Malhotra
A1 Amanda C Watts
A1 Lawrence C Wong
A1 Jasper A Estabillo
A1 Therese E Gadomski
A1 Oanh Hong
A1 Karin V Fuentes Fajardo
A1 Abhishek Bhandari
A1 Renius Owen
A1 Michael Baughn
A1 Jeffrey Yuan
A1 Terry Solomon
A1 Alexandra G Moyzis
A1 Stephan J Sanders
A1 Gail E Reiner
A1 Keith K Vaux
A1 Charles M Strom
A1 Kang Zhang
A1 Alysson R Muotri
A1 Natacha Akshoomoff
A1 Suzanne M Leal
A1 Karen Pierce
A1 Eric Courchesne
A1 Lilia M Iakoucheva
A1 Christina Corsello
A1 Jonathan Sebat
YR 2015
UL http://biorxiv.org/content/early/2015/10/30/030270.1.abstract
AB 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.