Ancestral components of admixed genomes in a Mexican cohort.
Ancestral components of admixed genomes in a Mexican cohort.
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DOI：
10.1371/journal.pgen.1002410
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发表时间：
2011-12
期刊：
影响因子：
4.5
通讯作者：
Tang H
中科院分区：
文献类型：
--
作者：
Johnson NA;Coram MA;Shriver MD;Romieu I;Barsh GS;London SJ;Tang H
对于世界上大多数地区来说，人类基因组结构在人口水平上是由古代地理隔离和最近的人口变化之间的相互作用形成的，这些因素分别被地理祖先和混合的概念所捕获。非混合个体的祖先通常可以追溯到一个精确地区的特定人群，但目前研究混合个体的方法通常会产生粗略的信息，其中基因组祖先比例是根据起源大陆确定的。在这里，我们介绍了一个新的分析策略，这个问题，允许细粒度的混合个人的地理和基因组坐标方面的特征。来自不同大陆的遗传学片段，用概率模型识别，用于构建和研究混合个体的“虚拟基因组”。我们将这种方法应用于一个队列的492个父母，子女三人组从墨西哥城。来自三个大陆水平的祖先种群-非洲，欧洲和美洲-的相对贡献在个体之间差异很大，单倍型块长度的分布表明混合时间为10-15代。每个墨西哥人的欧洲人和美洲土著虚拟基因组都可以追溯到每个大陆的精确地区，它们揭示了墨西哥西南部的土著人和尤卡坦半岛的玛雅人之间的美洲印第安人祖先的梯度。这与非洲裔美国人的非洲根源形成鲜明对比，非洲裔美国人的特点是多个西非人口的统一混合。我们还使用虚拟的欧洲人和美洲土著人的基因组来搜索祖先群体中选择的签名，我们确定了以前已知的其他群体中的选择目标，以及新的候选基因座。推断混合基因组的精确祖先组成部分的能力将有助于研究与疾病有关的表型，并将使人们能够对土著人民的适应历史和人口统计历史有新的了解。混合个体，如非洲裔美国人和拉丁美洲人，来自不同大陆的个体之间的交配。详细了解混合种群的祖先起源不仅可以了解种群本身的历史，而且还可以提供研究祖先种群进化生物学的机会。应用新的统计方法，我们分析了来自墨西哥城的近1,500名墨西哥人的高密度基因型数据，这些人混合在美洲土著人，欧洲人和非洲人中。来自三个大陆一级祖先种群的相对贡献在个体之间差异很大。这些墨西哥人的欧洲祖先在基因上与南欧人相似，如西班牙人和葡萄牙人。在我们的研究中，墨西哥人的美洲原住民祖先主要归因于居住在墨西哥西南部地区的土著群体，尽管有些人从尤卡坦半岛的玛雅人和其他美洲原住民那里继承了不同程度的祖先。对选择特征的搜索，集中在来自祖先群体（例如土著美国人）的基因组部分，确定了遗传变异可能在该祖先群体中受到自然选择青睐的区域。
For most of the world, human genome structure at a population level is shaped by interplay between ancient geographic isolation and more recent demographic shifts, factors that are captured by the concepts of biogeographic ancestry and admixture, respectively. The ancestry of non-admixed individuals can often be traced to a specific population in a precise region, but current approaches for studying admixed individuals generally yield coarse information in which genome ancestry proportions are identified according to continent of origin. Here we introduce a new analytic strategy for this problem that allows fine-grained characterization of admixed individuals with respect to both geographic and genomic coordinates. Ancestry segments from different continents, identified with a probabilistic model, are used to construct and study “virtual genomes” of admixed individuals. We apply this approach to a cohort of 492 parent–offspring trios from Mexico City. The relative contributions from the three continental-level ancestral populations—Africa, Europe, and America—vary substantially between individuals, and the distribution of haplotype block length suggests an admixing time of 10–15 generations. The European and Indigenous American virtual genomes of each Mexican individual can be traced to precise regions within each continent, and they reveal a gradient of Amerindian ancestry between indigenous people of southwestern Mexico and Mayans of the Yucatan Peninsula. This contrasts sharply with the African roots of African Americans, which have been characterized by a uniform mixing of multiple West African populations. We also use the virtual European and Indigenous American genomes to search for the signatures of selection in the ancestral populations, and we identify previously known targets of selection in other populations, as well as new candidate loci. The ability to infer precise ancestral components of admixed genomes will facilitate studies of disease-related phenotypes and will allow new insight into the adaptive and demographic history of indigenous people. Admixed individuals, such as African Americans and Latinos, arise from mating between individuals from different continents. Detailed knowledge about the ancestral origin of an admixed population not only provides insight regarding the history of the population itself, but also affords opportunities to study the evolutionary biology of the ancestral populations. Applying novel statistical methods, we analyzed the high-density genotype data of nearly 1,500 Mexican individuals from Mexico City, who are admixed among Indigenous Americans, Europeans, and Africans. The relative contributions from the three continental-level ancestral populations vary substantially between individuals. The European ancestors of these Mexican individuals genetically resemble Southern Europeans, such as the Spaniard and the Portuguese. The Indigenous American ancestry of the Mexicans in our study is largely attributed to the indigenous groups residing in the southwestern region of Mexico, although some individuals have inherited varying degrees of ancestry from the Mayans of the Yucatan Peninsula and other indigenous American populations. A search for signatures of selection, focusing on the parts of the genomes derived from an ancestral population (e.g. Indigenous American), identifies regions in which a genetic variant may have been favored by natural selection in that ancestral population.
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影响因子：
56.9
作者：
Rosenberg, NA;Pritchard, JK;Feldman, MW
通讯作者：
Feldman, MW
影响因子：
7
作者：
Pickrell, Joseph K.;Coop, Graham;Pritchard, Jonathan K.
通讯作者：
Pritchard, Jonathan K.
影响因子：
4.5
作者：
Bigham A;Bauchet M;Pinto D;Mao X;Akey JM;Mei R;Scherer SW;Julian CG;Wilson MJ;López Herráez D;Brutsaert T;Parra EJ;Moore LG;Shriver MD
通讯作者：
Shriver MD
影响因子：
5.8
作者：
Qin, Huaizhen;Morris, Nathan;Zhu, Xiaofeng
通讯作者：
Zhu, Xiaofeng
DOI：
10.1073/pnas.0914618107
发表时间：
2010-05-11
影响因子：
11.1
作者：
Bryc, Katarzyna;Velez, Christopher;Ostrer, Harry
通讯作者：
Ostrer, Harry