Journal article
Whole-Genome Sequencing in Autism Identifies Hot Spots for De Novo Germline Mutation
Cell (Cambridge), Vol.151(7), pp.1431-1442
12/21/2012
DOI: 10.1016/j.cell.2012.11.019
PMID: 23260136
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.
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► Whole-genome sequencing in autism reveals wide variation in regional mutation rates ► Regional mutability can be explained by intrinsic properties of DNA ► Dense mutation clusters can be explained by compound mutation or gene conversion ► Hypermutability is a characteristic of genes involved in human disease
Whole-genome sequencing of autism cases and controls reveals that mutation rates vary by up to 100-fold throughout the genome. Mutational hot spots may be explained by intrinsic characteristics of DNA sequence and chromatin structure and appear to be characteristic of genes involved in ASD and other diseases.
Details
- Title: Subtitle
- Whole-Genome Sequencing in Autism Identifies Hot Spots for De Novo Germline Mutation
- Creators
- Jacob J Michaelson - Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USAYujian Shi - School of Bioscience and Biotechnology, South China University of Technology, Guangzhou 510006, ChinaMadhusudan Gujral - Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USAHancheng Zheng - School of Bioscience and Biotechnology, South China University of Technology, Guangzhou 510006, ChinaDheeraj Malhotra - Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USAXin Jin - BGI-Shenzhen, Shenzhen 518083, ChinaMinghan Jian - BGI-Shenzhen, Shenzhen 518083, ChinaGuangming Liu - School of Computer Science, National University of Defense Technology, Changsha, Hunan 410073, ChinaDouglas Greer - Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USAAbhishek Bhandari - Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USAWenting Wu - Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USARoser Corominas - Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USAÁine Peoples - Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USAAmnon Koren - Department of Genetics, Harvard Medical School, Boston, MA 2115, USAAthurva Gore - Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USAShuli Kang - Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USAGuan Ning Lin - Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USAJasper Estabillo - Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USATherese Gadomski - Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USABalvindar Singh - Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USAKun Zhang - Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USANatacha Akshoomoff - Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USAChristina Corsello - Rady Children's Hospital, San Diego, CA 92123, USASteven McCarroll - Department of Genetics, Harvard Medical School, Boston, MA 2115, USALilia M Iakoucheva - Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USAYingrui Li - School of Bioscience and Biotechnology, South China University of Technology, Guangzhou 510006, ChinaJun Wang - University of CopenhagenJonathan Sebat - Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USA
- Resource Type
- Journal article
- Publication Details
- Cell (Cambridge), Vol.151(7), pp.1431-1442
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cell.2012.11.019
- PMID
- 23260136
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Language
- English
- Date published
- 12/21/2012
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Communication Sciences and Disorders; Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984070257202771
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