Human Y chromosome base-substitution mutation rate measured by direct sequencing in a deep-rooting pedigree.
Human Y chromosome base-substitution mutation rate measured by direct sequencing in a deep-rooting pedigree.
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DOI：
10.1016/j.cub.2009.07.032
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发表时间：
2009-09-15
期刊：
影响因子：
--
通讯作者：
Tyler-Smith C
中科院分区：
文献类型：
--
作者：
Xue Y;Wang Q;Long Q;Ng BL;Swerdlow H;Burton J;Skuce C;Taylor R;Abdellah Z;Zhao Y;Asan;MacArthur DG;Quail MA;Carter NP;Yang H;Tyler-Smith C
了解人类突变的关键过程对于医学遗传学和人类进化的许多方面都很重要。在过去，对突变率的估计通常是通过表型观察或密切相关物种之间的同源序列比较来推断的。在这里，我们应用新的测序技术来直接测量一个突变率，即人类Y染色体上碱基替换的突变率。对分离于13个世代的两个个体的Y染色体进行了流动排序，并用Illumina(Solexa)成对末端测序方法分别对其进行了平均深度11×和20×的测序。通过毛细管测序进一步检测来自捐赠者和其他家庭成员的细胞系和血DNA中的候选突变。在∼10.15Mb中确认了12个突变；其中8个发生在体外，4个发生在体内。后者可以放置在系谱上的不同位置，并导致突变率测量为3.0亿×10−8突变/核苷酸/世代(95%CI：8.9×10−9-7.0×10−8)，与已发表的人-黑猩猩Y染色体区域2.3×10−8-6.3x10−8突变/核苷酸/世代的估计一致，这取决于假设的世代和分裂时间。
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. 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. 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 in vitro and four in vivo. The latter could be placed in different positions on the pedigree and led to a mutation-rate measurement of 3.0 × 10−8 mutations/nucleotide/generation (95% CI: 8.9 × 10−9–7.0 × 10−8), consistent with estimates of 2.3 × 10−8–6.3 × 10−8 mutations/nucleotide/generation for the same Y-chromosomal region from published human-chimpanzee comparisons depending on the generation and split times assumed.
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影响因子：
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