The origins, determinants, and consequences of human mutations
- 25 September 2015
- journal article
- review article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 349 (6255), 1478-1483
- https://doi.org/10.1126/science.aaa9119
Abstract
Germline mutations are the principal cause of heritable disease and the ultimate source of evolutionary change. Similarly, somatic mutations are the primary cause of cancer and may contribute to the burden of human disease more broadly than previously appreciated. Here, we review recent insights into the rates, spectrum, and determinants of genomic mutations and how these parameters inform our understanding of both Mendelian and complex human diseases. We also consider models for conceptualizing mutational consequences and outline several key areas for future research, including the development of new technologies to access and quantify the full spectrum of mutations, as well as to better interpret the consequences of mutations with respect to molecular functionality, evolutionary fitness, and disease pathogenicity.Keywords
Funding Information
- NIH (R01GM110068, U01HG007591, DP1HG007811)
This publication has 60 references indexed in Scilit:
- Signatures of mutational processes in human cancerNature, 2013
- Detection of Clinically Relevant Genetic Variants in Autism Spectrum Disorder by Whole-Genome SequencingAmerican Journal of Human Genetics, 2013
- Estimating the human mutation rate using autozygosity in a founder populationNature Genetics, 2012
- Rate of de novo mutations and the importance of father’s age to disease riskNature, 2012
- Variation in genome-wide mutation rates within and between human familiesNature Genetics, 2011
- Genetic Heterogeneity in Human DiseaseCell, 2010
- High-resolution analysis of DNA regulatory elements by synthetic saturation mutagenesisNature Biotechnology, 2009
- Human mutation rate associated with DNA replication timingNature Genetics, 2009
- Next-generation DNA sequencingNature Biotechnology, 2008
- Genomic rearrangements and sporadic diseaseNature Genetics, 2007