Journal article
Differential Relationship of DNA Replication Timing to Different Forms of Human Mutation and Variation
American journal of human genetics, Vol.91(6), pp.1033-1040
12/07/2012
DOI: 10.1016/j.ajhg.2012.10.018
PMCID: PMC3516607
PMID: 23176822
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.
Details
- Title: Subtitle
- Differential Relationship of DNA Replication Timing to Different Forms of Human Mutation and Variation
- Creators
- Amnon Koren - Department of Genetics, Harvard Medical School, Boston, MA 02115, USAPaz Polak - Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USAJames Nemesh - Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USAJacob J Michaelson - Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USAJonathan Sebat - Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USAShamil R Sunyaev - Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USASteven A McCarroll - Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.91(6), pp.1033-1040
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.ajhg.2012.10.018
- PMID
- 23176822
- PMCID
- PMC3516607
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Language
- English
- Date published
- 12/07/2012
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Communication Sciences and Disorders; Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984070992102771
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