AI Article Synopsis
- De novo mutations significantly contribute to autism spectrum disorders (ASDs), with pathogenic copy number variants (CNVs) showing high mutation rates.
- The study involved whole-genome sequencing of monozygotic twins with ASD and their parents, revealing a 100-fold variation in mutation rates across the genome, influenced by DNA sequence and chromatin structure.
- Findings indicated that hypermutability is prevalent in ASD-related genes, which may increase disease risk and highlight the importance of regional mutation patterns in genetic variation.
Article 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712641 | PMC |
| http://dx.doi.org/10.1016/j.cell.2012.11.019 | DOI Listing |
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