Human Y Chromosome Base-Substitution Mutation Rate Measured by Direct Sequencing in a Deep-Rooting Pedigree // Current Biology, 27 August 2009

Xue et al

Summary

Understanding the key process of human mutation is important for many aspects of medical genetics and human evolution. In the past, estimates of mutation rates have generally been inferred from phenotypic observations or comparisons of homologous sequences among closely related species [1,2,3]. Here, we apply new sequencing technology to measure directly one mutation rate, that of base substitutions on the human Y chromosome. The Y chromosomes of two individuals separated by 13 generations were flow sorted and sequenced by Illumina (Solexa) paired-end sequencing to an average depth of 11 or 20, respectively [4]. Candidate mutations were further examined by capillary sequencing in cell-line and blood DNA from the donors and additional family members. Twelve mutations were confirmed in 10.15 Mb; eight of these had occurred invitro and four invivo. The latter could be placed in different positions on the pedigree and led to a mutation-rate measurement of 3.0 108 mutations/nucleotide/generation (95% CI: 8.9 1097.0 108), consistent with estimates of 2.3 1086.3 108 mutations/nucleotide/generation for the same Y-chromosomal region from published human-chimpanzee comparisons [5] depending on the generation and split times assumed.

http://www.cell.com/current-biology/abstract/S0960-9822%2809%2901454-7