Whole-genome sequencing in autism identifies hot spots for de novo germline mutation
| Autor: | Jasper A. Estabillo, Roser Corominas, Hancheng Zheng, Amnon Koren, Natacha Akshoomoff, Athurva Gore, Christina Corsello, Dheeraj Malhotra, Jacob J. Michaelson, Steven A. McCarroll, Aine Peoples, Xin Jin, Abhishek Bhandari, Yingrui Li, Guan Ning Lin, Wenting Wu, Yujian Shi, Shuli Kang, Madhusudan Gujral, Guangming Liu, Balvindar Singh, Jonathan Sebat, Minghan Jian, Kun Zhang, Douglas S. Greer, Jun Wang, Therese E. Gadomski, Lilia M. Iakoucheva |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Mutation rate Pan troglodytes Somatic hypermutation Genome-wide association study Biology Genome Article General Biochemistry Genetics and Molecular Biology Paternal Age Cell Line Germline mutation Mutation Rate mental disorders Animals Humans Copy-number variation Autistic Disorder Germ-Line Mutation Whole genome sequencing Genetics Biochemistry Genetics and Molecular Biology(all) Exons Sequence Analysis DNA Twins Monozygotic Mutation (genetic algorithm) Female Genome-Wide Association Study Maternal Age |
| Zdroj: | Cell. 151(7) |
| ISSN: | 1097-4172 |
| Popis: | SummaryDe 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.PaperFlick |
| Databáze: | OpenAIRE |
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