%0 Journal Article %1 campbell2012estimating %A Campbell, C D %A Chong, J X %A Malig, M %A Ko, A %A Dumont, B L %A Han, L %A Vives, L %A O'Roak, B J %A Sudmant, P H %A Shendure, J %A Abney, M %A Ober, C %A Eichler, E E %D 2012 %J Nat Genet %K mutation_rate mutation_rate_estimation short_read_data %N 11 %P 1277-1281 %R 10.1038/ng.2418 %T Estimating the human mutation rate using autozygosity in a founder population %U http://www.ncbi.nlm.nih.gov/pubmed/23001126 %V 44 %X 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.

@article{campbell2012estimating, 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.}, added-at = {2014-10-10T21:08:53.000+0200}, author = {Campbell, C D and Chong, J X and Malig, M and Ko, A and Dumont, B L and Han, L and Vives, L and O'Roak, B J and Sudmant, P H and Shendure, J and Abney, M and Ober, C and Eichler, E E}, biburl = {https://www.bibsonomy.org/bibtex/29b8f23768929bbd94db5f2676a2278f2/peter.ralph}, doi = {10.1038/ng.2418}, interhash = {b7561323be59ef100c7b3e3e3b72e094}, intrahash = {9b8f23768929bbd94db5f2676a2278f2}, journal = {Nat Genet}, keywords = {mutation_rate mutation_rate_estimation short_read_data}, month = nov, number = 11, pages = {1277-1281}, pmid = {23001126}, timestamp = {2014-10-10T21:08:53.000+0200}, title = {Estimating the human mutation rate using autozygosity in a founder population}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23001126}, volume = 44, year = 2012 }