Whole-genome sequencing in autism identifies hot spots for de novo germline mutation
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Cell |
Volume | 151 |
Issue number | 7 |
Pages (from-to) | 1431-1442 |
Number of pages | 12 |
ISSN | 0092-8674 |
DOIs | |
Publication status | Published - 2012 |
ID: 46094140