Details

Autor(en) / Beteiligte

• 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, Áine
• 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

Titel

Whole-Genome Sequencing in Autism Identifies Hot Spots for De Novo Germline Mutation

Ist Teil von

• Cell, 2012-12, Vol.151 (7), p.1431-1442

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] [Display omitted] ► 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.