Whole-genome sequencing in autism identifies hot spots for de novo germline mutation

Michaelson, Jacob J., Shi, Yujian, Gujral, Madhusudan, Zheng, Hancheng, Malhotra, Dheeraj, Jin, Xin, Jian, Minghan, Liu, Guangming, Greer, Douglas, Bhandari, Abhishek, Wu, Wenting, Corominas, Roser, Peoples, Aine, Koren, Amnon, Gore, Athurva, Kang, Shuli, Lin, Guan Ning, Estabillo, Jasper, Gadomski, Therese, Singh, Balvindar, Zhang, Kun, Akshoomoff, Natacha, Corsello, Christina, McCarroll, Steven, Iakoucheva, Lilia M., Li, Yingrui, Wang, Jun and Sebat, Jonathan (2012) Whole-genome sequencing in autism identifies hot spots for de novo germline mutation. Cell, 151 7: 1431-1442. doi:10.1016/j.cell.2012.11.019

Author Michaelson, Jacob J.
Shi, Yujian
Gujral, Madhusudan
Zheng, Hancheng
Malhotra, Dheeraj
Jin, Xin
Jian, Minghan
Liu, Guangming
Greer, Douglas
Bhandari, Abhishek
Wu, Wenting
Corominas, Roser
Peoples, Aine
Koren, Amnon
Gore, Athurva
Kang, Shuli
Lin, Guan Ning
Estabillo, Jasper
Gadomski, Therese
Singh, Balvindar
Zhang, Kun
Akshoomoff, Natacha
Corsello, Christina
McCarroll, Steven
Iakoucheva, Lilia M.
Li, Yingrui
Wang, Jun
Sebat, Jonathan
Title Whole-genome sequencing in autism identifies hot spots for de novo germline mutation
Journal name Cell   Check publisher's open access policy
ISSN 0092-8674
Publication date 2012-12-21
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.cell.2012.11.019
Open Access Status Not yet assessed
Volume 151
Issue 7
Start page 1431
End page 1442
Total pages 12
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
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. PaperFlick:
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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