Details

Autor(en) / Beteiligte

• Michaelson, Jacob J.
• Shi, Yujian
• Gujral, Madhusudan
• Zheng, Hancheng
• Malhotra, Dheeraj
• Jin, Xin
• Minghan, Jian
• 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 Hotspots for De Novo Germline Mutation

Ist Teil von

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

Erscheinungsjahr

2012

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

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 hotspots. 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 datasets. Our findings suggest that regional hypermutation is a significant factor shaping patterns of genetic variation and disease risk in humans.