Using multi-way admixture mapping to elucidate TB susceptibility in the South African Coloured population.
Using multi-way admixture mapping to elucidate TB susceptibility in the South African Coloured population.
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DOI：
10.1186/1471-2164-15-1021
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发表时间：
2014-11-25
期刊：
影响因子：
4.4
通讯作者：
Hoal EG
中科院分区：
文献类型：
--
作者：
Daya M;van der Merwe L;Gignoux CR;van Helden PD;Möller M;Hoal EG
混合的南非有色人种非常适合发现结核病易感性遗传变异及其可能的种族起源，但先前使用全基因组混合作图发现此类变异的尝试受到当地祖先推断不准确的阻碍。在这项研究中，我们使用RFMix中实现的新算法推断当地祖先，重点是识别过量的San或Bantu祖先区域，我们假设这些区域可能含有结核病易感基因。利用模拟数据，我们证明了RFMix对本地祖先的推断具有合理的准确性，但存在将San祖先误称为班图人的倾向。拥有过多桑人祖先或过多非洲人（桑人或班图人）祖先的地区不太可能受到这种偏倚的影响，因此我们继续确定这些地区，在病例中发现，但在对照中没有发现（642例和91例对照）。研究人员发现了许多有希望的区域（San祖先的总体p值为7.19×10-5，非洲祖先的p值为<2.00×10-16），包括染色体15q15和17q22，它们与以前涉及结核病的基因组区域接近。有希望的免疫相关易感基因，如GADD45A， OSM和B7-H5基因也存在于鉴定的区域。混合定位在南非有色人种中是可行的，并且发现了一些新的结核病易感基因组区域。本文的在线版本（doi:10.1186/1471-2164-15-1021）包含补充材料，可供授权用户使用。
The admixed South African Coloured population is ideally suited to the discovery of tuberculosis susceptibility genetic variants and their probable ethnic origins, but previous attempts at finding such variants using genome-wide admixture mapping were hampered by the inaccuracy of local ancestry inference. In this study, we infer local ancestry using the novel algorithm implemented in RFMix, with the emphasis on identifying regions of excess San or Bantu ancestry, which we hypothesize may harbour TB susceptibility genes. Using simulated data, we demonstrate reasonable accuracy of local ancestry inference by RFMix, with a tendency towards miss-calling San ancestry as Bantu. Regions with either excess San ancestry or excess African (San or Bantu) ancestry are less likely to be affected by this bias, and we therefore proceeded to identify such regions, found in cases but not in controls (642 cases and 91 controls). A number of promising regions were found (overall p-values of 7.19×10-5 for San ancestry and <2.00×10-16 for African ancestry), including chromosomes 15q15 and 17q22, which are close to genomic regions previously implicated in TB. Promising immune-related susceptibility genes such as the GADD45A, OSM and B7-H5 genes are also harboured in the identified regions. Admixture mapping is feasible in the South African Coloured population and a number of novel TB susceptibility genomic regions were uncovered. The online version of this article (doi:10.1186/1471-2164-15-1021) contains supplementary material, which is available to authorized users.
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DOI：
10.1126/science.1172257
发表时间：
2009-05-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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Williams SM
DOI：
10.1038/nrg3002
发表时间：
2011-06-28
期刊：
Nature reviews. Genetics
影响因子：
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作者：
通讯作者：
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影响因子：
3.5
作者：
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通讯作者：
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影响因子：
3.2
作者：
Moeller, Marlo;Nebel, Almut;Hoal, Eileen G.
通讯作者：
Hoal, Eileen G.
DOI：
10.1126/science.1227721
发表时间：
2012-10-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Schlebusch CM;Skoglund P;Sjödin P;Gattepaille LM;Hernandez D;Jay F;Li S;De Jongh M;Singleton A;Blum MG;Soodyall H;Jakobsson M
通讯作者：
Jakobsson M