Details

Autor(en) / Beteiligte

• CAMPBELL, Catarina D
• CHONG, Jessica X
• ABNEY, Mark
• OBER, Carole
• EICHLER, Evan E
• MALIG, Maika
• KO, Arthur
• DUMONT, Beth L
• LIDE HAN
• VIVES, Laura
• O'ROAK, Brian J
• SUDMANT, Peter H
• SHENDURE, Jay

Titel

Estimating the human mutation rate using autozygosity in a founder population

Ist Teil von

• Nature genetics, 2012-11, Vol.44 (11), p.1277-1281

Ort / Verlag

New York, NY: Nature Publishing Group

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.