Differential relationship of DNA replication timing to different forms of human mutation and variation.

Am J Hum Genet
Authors
Keywords
Abstract

Human genetic variation is distributed nonrandomly across the genome, though the principles governing its distribution are only partially known. DNA replication creates opportunities for mutation, and the timing of DNA replication correlates with the density of SNPs across the human genome. To enable deeper investigation of how DNA replication timing relates to human mutation and variation, we generated a high-resolution map of the human genome's replication timing program and analyzed its relationship to point mutations, copy number variations, and the meiotic recombination hotspots utilized by males and females. DNA replication timing associated with point mutations far more strongly than predicted from earlier analyses and showed a stronger relationship to transversion than transition mutations. Structural mutations arising from recombination-based mechanisms and recombination hotspots used more extensively by females were enriched in early-replicating parts of the genome, though these relationships appeared to relate more strongly to the genomic distribution of causative sequence features. These results indicate differential and sex-specific relationship of DNA replication timing to different forms of mutation and recombination.

Year of Publication
2012
Journal
Am J Hum Genet
Volume
91
Issue
6
Pages
1033-40
Date Published
2012 Dec 07
ISSN
1537-6605
URL
DOI
10.1016/j.ajhg.2012.10.018
PubMed ID
23176822
PubMed Central ID
PMC3516607
Links
Grant list
R01 MH076431 / MH / NIMH NIH HHS / United States