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Open AccessJournal ArticleDOI

Strong male bias drives germline mutation in chimpanzees

TLDR
Overall, the mutation rate per year in chimps is similar to that in humans, but the male mutation bias with age is stronger, and mutation rates and patterns differ between closely related species.
Abstract
Germline mutation determines rates of molecular evolution, genetic diversity, and fitness load. In humans, the average point mutation rate is 1.2 × 10−8 per base pair per generation, with every additional year of father’s age contributing two mutations across the genome and males contributing three to four times as many mutations as females. To assess whether such patterns are shared with our closest living relatives, we sequenced the genomes of a nine-member pedigree of Western chimpanzees, Pan troglodytes verus. Our results indicate a mutation rate of 1.2 × 10−8 per base pair per generation, but a male contribution seven to eight times that of females and a paternal age effect of three mutations per year of father’s age. Thus, mutation rates and patterns differ between closely related species.

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Journal ArticleDOI

Genetic drift, selection and the evolution of the mutation rate

TL;DR: This work concludes that the drift-barrier hypothesis is consistent with comparative measures of mutation rates, provides a simple explanation for the existence of error-prone polymerases and yields a formal counter-argument to the view that selection fine-tunes gene-specific mutation rates.
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Timing, rates and spectra of human germline mutation

TL;DR: The data suggest that the mutation rate per cell division is higher during both early embryogenesis and differentiation of primordial germ cells but is reduced substantially during post-pubertal spermatogenesis, which has important consequences for the recurrence risks of disorders caused by de novo mutations.
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Determinants of genetic diversity

TL;DR: Comparative population genomics is on its way to providing a solution to 'Lewontin's paradox' — the discrepancy between the many orders of magnitude of variation in population size and the much narrower distribution of diversity levels.
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Determinants of Mutation Rate Variation in the Human Germline

TL;DR: It is now feasible to count de novo mutations in transmissions from parents to offspring, and this direct approach yields a mutation rate that is twofold lower than previous estimates, calling into question the authors' understanding of the chronology of human evolution and raising the possibility that mutation rates have evolved relatively rapidly.
References
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Journal ArticleDOI

The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data

TL;DR: The GATK programming framework enables developers and analysts to quickly and easily write efficient and robust NGS tools, many of which have already been incorporated into large-scale sequencing projects like the 1000 Genomes Project and The Cancer Genome Atlas.
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The estimation of map distances from recombination values.

TL;DR: The genetic map is a tool to quantify the distance between genes on a chromosome, based on the observed frequency of crossovers during cell division, which is used to estimate the total distance between chromosomes.
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Merlin--rapid analysis of dense genetic maps using sparse gene flow trees.

TL;DR: The multipoint engine for rapid likelihood inference (Merlin) is a computer program that uses sparse inheritance trees for pedigree analysis; it performs rapid haplotyping, genotype error detection and affected pair linkage analyses and can handle more markers than other pedigree analysis packages.
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A high-resolution recombination map of the human genome

TL;DR: Recombination rates are significantly correlated with both cytogenetic structures and sequence and paternal chromosomes show many differences in locations of recombination maxima, suggesting that there is some underlying component determined by both genetic and environmental factors that affects maternal recombination rates.
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