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为夏威夷原住民量身定制的重组图谱提高了正向选择基因组扫描的稳健性。

Recombination map tailored to Native Hawaiians improves robustness of genomic scans for positive selection.

作者信息

Dinh Bryan L, Tang Echo, Taparra Kekoa, Nakatsuka Nathan, Chen Fei, Chiang Charleston W K

机构信息

Department of Quantitative and Computational Biology, University of Southern California.

Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California.

出版信息

bioRxiv. 2023 Sep 2:2023.07.12.548735. doi: 10.1101/2023.07.12.548735.

Abstract

Recombination events establish the patterns of haplotypic structure in a population and estimates of recombination rates are used in several downstream population and statistical genetic analyses. Using suboptimal maps from distantly related populations may reduce the efficacy of genomic analyses, particularly for underrepresented populations such as the Native Hawaiians. To overcome this challenge, we constructed recombination maps using genome-wide array data from two study samples of Native Hawaiians: one reflecting the current admixed state of Native Hawaiians (NH map), and one based on individuals of enriched Polynesian ancestries (PNS map) with the potential to be used for less admixed Polynesian populations such as the Samoans. We found the recombination landscape to be less correlated with those from other continental populations (e.g. Spearman's rho = 0.79 between PNS and CEU (Utah residents with Northern and Western European ancestry) compared to 0.92 between YRI (Yoruba in Ibadan, Nigeria) and CEU at 50 kb resolution), likely driven by the unique demographic history of the Native Hawaiians. PNS also shared the fewest recombination hotspots with other populations (e.g. 8% of hotspots shared between PNS and CEU compared to 27% of hotspots shared between YRI and CEU). We found that downstream analyses in the Native Hawaiian population, such as local ancestry inference, imputation, and IBD segment and relatedness detections, would achieve similar efficacy when using the NH map compared to an omnibus map. However, for genome scans of adaptive loci using integrated haplotype scores, we found several loci with apparent genome-wide significant signals (|Z-score| > 4) in Native Hawaiians that would not have been significant when analyzed using NH-specific maps. Population-specific recombination maps may therefore improve the robustness of haplotype-based statistics and help us better characterize the evolutionary history that may underlie Native Hawaiian-specific health conditions that persist today.

摘要

重组事件确立了群体中单体型结构的模式,重组率估计值被用于多个下游群体和统计遗传学分析中。使用来自远缘群体的次优图谱可能会降低基因组分析的效能,对于像夏威夷原住民这样代表性不足的群体尤其如此。为了克服这一挑战,我们利用来自两个夏威夷原住民研究样本的全基因组阵列数据构建了重组图谱:一个反映夏威夷原住民当前的混合状态(NH图谱),另一个基于波利尼西亚血统富集个体(PNS图谱),该图谱有可能用于像萨摩亚人这样混合程度较低的波利尼西亚群体。我们发现,重组格局与其他大陆群体的重组格局相关性较低(例如,在50kb分辨率下,PNS与CEU(犹他州具有北欧和西欧血统的居民)之间的斯皮尔曼相关系数为0.79,而YRI(尼日利亚伊巴丹的约鲁巴人)与CEU之间为0.92),这可能是由夏威夷原住民独特的人口历史所驱动的。PNS与其他群体共享的重组热点也最少(例如,PNS与CEU之间共享8%的热点,而YRI与CEU之间共享27%的热点)。我们发现,在夏威夷原住民群体中进行下游分析,如本地祖先推断、基因填充以及IBD片段和亲属关系检测,使用NH图谱与综合图谱相比能达到相似的效能。然而,对于使用综合单倍型分数进行的适应性位点全基因组扫描,我们发现在夏威夷原住民中有几个位点具有明显的全基因组显著信号(|Z分数|>4),而使用特定于NH的图谱进行分析时这些位点并不显著。因此,群体特异性重组图谱可能会提高基于单倍型统计的稳健性,并帮助我们更好地描绘可能是当今夏威夷原住民特有健康状况基础的进化历史。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f88/10486861/f70c758e3b47/nihpp-2023.07.12.548735v2-f0001.jpg

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