由中、美、英等多个国家共同发起的大型国际合作项目“千人基因组计划”的最新研究成果在《自然》(Nature)上在线发表。该协作组公布了高分辨率的人类基因组遗传变异整合图谱,将为基因组学在人类疾病与健康领域中的应用以及个体化医疗时代的到来奠定了坚实的科学基础。

-2012年11月1日《自然》

中文翻译


【题目】来自1092个人类基因组的遗传变异综合图谱

【译文】通过绘制人类遗传变异的地理和功能谱,千人基因组计划旨在建立一个遗传因素促进疾病发生的数据库。本研究采用结合低覆盖度全基因组和外显子组的测序方法,获得来自14个种群的1092个个体的基因组信息。本研究开发出一种整合一些算法和多种数据资源间信息的方法,我们提供了一个包含3800万个单核苷酸多态性、140万个短插入和缺失以及超过14000个更大缺失的单倍体图谱。本研究表明来自不同种群的个体携带有稀少和常见突变体的不同图谱,且低频变异表现出了本质的地理差异,这可通过净化选择行为进一步提高。我们的研究表明进化保守和编码结果是净化选择强度的关键决定因素,稀少突变负荷实质上改变了生物学途径,而且每个个体包含有保守位点上数以百计的稀有非编码突变,例如转录因子结合位点内基序破坏性变化。这种资源获得了高达98%的可理解的单核苷酸多态性,它们在相关人群中的频率为1%,使得我们可以分析来自不同的,包括混合群体的个体中常见的和低频突的变体。

英文原稿


[Title]: An integrated map of genetic variation from 1,092 human genomes

[Authors]:The 1000 Genomes Project Consortium

[Abstract]:By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations.

原文地址

http://www.nature.com/nature/journal/v491/n7422/full/nature11632.html

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