Estimating the human mutation rate from autozygous segments reveals population differences in human mutational processes
Open Access
- 21 August 2017
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 8 (1), 1-7
- https://doi.org/10.1038/s41467-017-00323-y
Abstract
Heterozygous mutations within homozygous sequences descended from a recent common ancestor offer a way to ascertain de novo mutations across multiple generations. Using exome sequences from 3222 British-Pakistani individuals with high parental relatedness, we estimate a mutation rate of 1.45 ± 0.05 × 10−8 per base pair per generation in autosomal coding sequence, with a corresponding non-crossover gene conversion rate of 8.75 ± 0.05 × 10−6 per base pair per generation. This is at the lower end of exome mutation rates previously estimated in parent–offspring trios, suggesting that post-zygotic mutations contribute little to the human germ-line mutation rate. We find frequent recurrence of mutations at polymorphic CpG sites, and an increase in C to T mutations in a 5ʹ CCG 3ʹ to 5ʹ CTG 3ʹ context in the Pakistani population compared to Europeans, suggesting that mutational processes have evolved rapidly between human populations.This publication has 31 references indexed in Scilit:
- Signatures of mutational processes in human cancerNature, 2013
- Estimating the human mutation rate using autozygosity in a founder populationNature Genetics, 2012
- Revising the human mutation rate: implications for understanding human evolutionNature Reviews Genetics, 2012
- Rate of de novo mutations and the importance of father’s age to disease riskNature, 2012
- Fine-scale recombination rate differences between sexes, populations and individualsNature, 2010
- The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing dataGenome Research, 2010
- Human Genome Sequencing Using Unchained Base Reads on Self-Assembling DNA NanoarraysScience, 2010
- The Sequence Alignment/Map format and SAMtoolsBioinformatics, 2009
- Enhanced diabetes care to patients of south Asian ethnic origin (the United Kingdom Asian Diabetes Study): a cluster randomised controlled trialThe Lancet, 2008
- Quantification of Homozygosity in Consanguineous Individuals with Autosomal Recessive DiseaseAmerican Journal of Human Genetics, 2006