Taxa de mutação humana revelada

Human Y Chromosome Base-Substitution Mutation Rate Measured by Direct Sequencing in a Deep-Rooting Pedigree

Yali Xue1,,,Qiuju Wang2,Quan Long1,Bee Ling Ng1,Harold Swerdlow1,John Burton1,Carl Skuce1,Ruth Taylor1,Zahra Abdellah1,Yali Zhao2,Asan1,Daniel G. MacArthur1,Michael A. Quail1,Nigel P. Carter1,Huanming Yang3andChris Tyler-Smith1,,

1 The Wellcome Trust Sanger Institute, Hinxton, Cambs CB10 1SA, UK

2 Department of Otorhinolaryngology-Head and Neck Surgery and Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853, China

3 Beijing Genomics Institute at Shenzhen, Shenzhen 518000, China

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 3.0108 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.

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