Unknown

Dataset Information

0

Estimating the human mutation rate using autozygosity in a founder population.


ABSTRACT: Knowledge of the rate and pattern of new mutation is critical to the understanding of human disease and evolution. We used extensive autozygosity in a genealogically well-defined population of Hutterites to estimate the human sequence mutation rate over multiple generations. We sequenced whole genomes from 5 parent-offspring trios and identified 44 segments of autozygosity. Using the number of meioses separating each pair of autozygous alleles and the 72 validated heterozygous single-nucleotide variants (SNVs) from 512 Mb of autozygous DNA, we obtained an SNV mutation rate of 1.20 × 10(-8) (95% confidence interval 0.89-1.43 × 10(-8)) mutations per base pair per generation. The mutation rate for bases within CpG dinucleotides (9.72 × 10(-8)) was 9.5-fold that of non-CpG bases, and there was strong evidence (P = 2.67 × 10(-4)) for a paternal bias in the origin of new mutations (85% paternal). We observed a non-uniform distribution of heterozygous SNVs (both newly identified and known) in the autozygous segments (P = 0.001), which is suggestive of mutational hotspots or sites of long-range gene conversion.

SUBMITTER: Campbell CD 

PROVIDER: S-EPMC3483378 | BioStudies | 2012-01-01

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC4803638 | BioStudies
2012-01-01 | S-EPMC3325203 | BioStudies
2011-01-01 | S-EPMC3188534 | BioStudies
2017-01-01 | S-EPMC5566399 | BioStudies
2016-01-01 | S-EPMC5016959 | BioStudies
1000-01-01 | S-EPMC5759835 | BioStudies
2016-01-01 | S-EPMC5147774 | BioStudies
2011-01-01 | S-EPMC3819807 | BioStudies
1000-01-01 | S-EPMC4866527 | BioStudies
2020-01-01 | S-EPMC7046685 | BioStudies