
最近的基因分型技术给理解复杂疾病等相关问题带来了空前的机遇。进行这项研究的最大障碍是潜在的亚群之间能产生假象联系。之前的研究大都采用基因分型、平行比较对照和病例组的基因频率等方法。这种方法很难观察到人群原始的基因结构。
加州大学和卡耐基-梅隆大学的科学家们开发出了一个新的研究混合人群中当地祖先(LAMP)的方法。这个方法推断出个体在每个单核苷酸多肽位点的祖先。LAMP通过计算SNPs邻近的重叠区域并结合大多数公认的结果来确定人群的亚结构。LAMP可用于估计个体的基因混合程度。实践证明,这项技术在评估混合人群的祖先基因中比STRUCTURE和SABER更精确、更高效,而且无需分型祖先基因。
相关论文发表在爱思唯尔期刊《美国人类遗传学杂志》(The American Journal of Human Genetics)上。(科学新闻杂志 周瑞霞/编译)
(《美国人类遗传学杂志》(The American Journal of Human Genetics),Volume 82, Issue 2, 290-303,Sriram Sankararaman,Eran Halperin)
Estimating Local Ancestry in Admixed Populations
Sriram Sankararaman1, Srinath Sridhar, Gad Kimmel1 and Eran Halperin, ,
1 Computer Science Deptartment, University of California, Berkeley, Berkeley, CA 94720, USA
2 Computer Science Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA
3 International Computer Science Institute, Berkeley, CA 94704, USA
Large-scale genotyping of SNPs has shown a great promise in identifying markers that could be linked to diseases. One of the major obstacles involved in performing these studies is that the underlying population substructure could produce spurious associations. Population substructure can be caused by the presence of two distinct subpopulations or a single pool of admixed individuals. In this work, we focus on the latter, which is significantly harder to detect in practice. New advances in this research direction are expected to play a key role in identifying loci that are different among different populations and are still associated with a disease. We evaluated current methods for inference of population substructure in such cases and show that they might be quite inaccurate even in relatively simple scenarios. We therefore introduce a new method, LAMP (Local Ancestry in adMixed Populations), which infers the ancestry of each individual at every single-nucleotide polymorphism (SNP). LAMP computes the ancestry structure for overlapping windows of contiguous SNPs and combines the results with a majority vote. Our empirical results show that LAMP is significantly more accurate and more efficient than existing methods for inferrring locus-specific ancestries, enabling it to handle large-scale datasets. We further show that LAMP can be used to estimate the individual admixture of each individual. Our experimental evaluation indicates that this extension yields a considerably more accurate estimate of individual admixture than state-of-the-art methods such as STRUCTURE or EIGENSTRAT, which are frequently used for the correction of population stratification in association studies.
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