nature-genetic201211-15

来自美国华盛顿大学的Evan Eichler及其同事基于来自哈特教派信徒群体、5个父母孩子的三人家庭的全基因组测序结果和来自其他血统的基因分型数据,估计了人类的突变频率。他们使用一种新方法来估计过去多代的突变频率,并考虑了来自创始者居群的大量同接合性。相关的研究论文于9月23日在线发表在《Nature Genetics》期刊上。

-2012年11月《自然-遗传》

中文翻译


【题目】借助创始者居群的同接合性来估计人类的突变频率

【译文】 对新突变的发生频率和模式的了解是理解人类疾病和进化的关键。我们借助在血统确定的、哈特教派信徒群体中发现的大量同接合性来估计过去多代的人类基因组序列的突变频率。我们对来自5个父母孩子的三人家庭的全基因组进行了测序,鉴定到44个同接合性的片段。借助减数分裂分离的自系纯合等位基因的数目和来自大小为512Mb、自系纯合的DNA的72个证实的杂合型单核苷酸变异(SNVs),我们确定了单核苷酸变异频率为1.20 × 10−8个突变/碱基对/世代(95%的置信区间为0.89–1.43 × 10−8)。CpG二核苷酸内的碱基突变频率(9.72 × 10−8)是非CpG碱基的9.5倍,且有有力的证据表明在新突变的来源中有严重的父系倾向(85%来源父亲)。我们发现杂合的单核苷酸变异在自系纯合片段中不均匀分布(P = 0.001)(无论是新鉴定的还是已知的),这暗示了自系纯合片段是突变的热点或长片段基因转换的位点。

英文原稿


[Title]: Estimating the human mutation rate using autozygosity in a founder population

[Authors]: Catarina D Campbell, Jessica X Chong, Maika Malig, Arthur Ko, Beth L Dumont, Lide Han, Laura Vives, Brian J O’Roak, Peter H Sudmant, Jay Shendure, Mark Abney, Carole Ober & Evan E Eichler

[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.

原文地址

http://www.nature.com/ng/journal/v44/n11/full/ng.2418.html

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