| Literature DB >> 23260136 |
Jacob J Michaelson1, Yujian Shi, Madhusudan Gujral, Hancheng Zheng, Dheeraj Malhotra, Xin Jin, Minghan Jian, Guangming Liu, Douglas Greer, Abhishek Bhandari, Wenting Wu, Roser Corominas, Aine Peoples, Amnon Koren, Athurva Gore, Shuli Kang, Guan Ning Lin, Jasper Estabillo, Therese Gadomski, Balvindar Singh, Kun Zhang, Natacha Akshoomoff, Christina Corsello, Steven McCarroll, Lilia M Iakoucheva, Yingrui Li, Jun Wang, Jonathan Sebat.
Abstract
De novo mutation plays an important role in autism spectrum disorders (ASDs). Notably, pathogenic copy number variants (CNVs) are characterized by high mutation rates. We hypothesize that hypermutability is a property of ASD genes and may also include nucleotide-substitution hot spots. We investigated global patterns of germline mutation by whole-genome sequencing of monozygotic twins concordant for ASD and their parents. Mutation rates varied widely throughout the genome (by 100-fold) and could be explained by intrinsic characteristics of DNA sequence and chromatin structure. Dense clusters of mutations within individual genomes were attributable to compound mutation or gene conversion. Hypermutability was a characteristic of genes involved in ASD and other diseases. In addition, genes impacted by mutations in this study were associated with ASD in independent exome-sequencing data sets. Our findings suggest that regional hypermutation is a significant factor shaping patterns of genetic variation and disease risk in humans.Entities:
Mesh：
Year: 2012 PMID： 23260136 PMCID： PMC3712641 DOI： 10.1016/j.cell.2012.11.019
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582