Genetic ancestry and diagnostic yield of exome sequencing in a diverse population.
Genetic ancestry and diagnostic yield of exome sequencing in a diverse population.
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DOI：
10.1038/s41525-023-00385-6
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发表时间：
2024-01-03
影响因子：
5.3
通讯作者：
Risch, Neil
中科院分区：
文献类型：
--
作者：
Mavura, Yusuph;Sahin-Hodoglugil, Nuriye;Hodoglugil, Ugur;Kvale, Mark;Martin, Pierre-Marie;Van Ziffle, Jessica;Devine, W. Patrick;Ackerman, Sara L.;Koenig, Barbara A.;Kwok, Pui-Yan;Norton, Mary E.;Slavotinek, Anne;Risch, Neil
已经表明，外显子组测序（ES）的诊断率（DY）在非欧洲血统的患者中可能低于欧洲血统的患者。我们在一个种族/民族多样的儿科和产前临床队列中研究了DY与估计的大陆/次大陆遗传祖先的关系。845例疑似遗传性疾病患者行ES诊断。大陆/次大陆的遗传祖先的比例估计从ES数据。我们通过Kolmogorov-Smirnov检验比较了阳性、阴性和不确定病例中遗传祖先的分布，并通过Cochran-Armitage趋势检验比较了祖先与DY的线性相关性。我们没有观察到与任何遗传血统（非洲人、美洲原住民、东亚人、欧洲人、中东人、南亚人）相关的总体DY降低。然而，我们观察到，由于血缘关系，与中东和南亚血统相关的其他遗传模式相比，常染色体隐性纯合子遗传的比例相对增加。在未诊断的儿科和产前遗传条件的ES的实证研究中，遗传血统与阳性诊断的可能性无关，支持在所有祖先人群中公平使用ES诊断以前未诊断但可能是孟德尔疾病。
It has been suggested that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental/subcontinental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort. Cases (N = 845) with suspected genetic disorders underwent ES for diagnosis. Continental/subcontinental genetic ancestry proportions were estimated from the ES data. We compared the distribution of genetic ancestries in positive, negative, and inconclusive cases by Kolmogorov–Smirnov tests and linear associations of ancestry with DY by Cochran-Armitage trend tests. We observed no reduction in overall DY associated with any genetic ancestry (African, Native American, East Asian, European, Middle Eastern, South Asian). However, we observed a relative increase in proportion of autosomal recessive homozygous inheritance versus other inheritance patterns associated with Middle Eastern and South Asian ancestry, due to consanguinity. In this empirical study of ES for undiagnosed pediatric and prenatal genetic conditions, genetic ancestry was not associated with the likelihood of a positive diagnosis, supporting the equitable use of ES in diagnosis of previously undiagnosed but potentially Mendelian disorders across all ancestral populations.
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DOI：
10.1097/gim.0b013e3181f8baad
发表时间：
2010-11
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Manning M;Hudgins L;Professional Practice and Guidelines Committee
通讯作者：
Professional Practice and Guidelines Committee
影响因子：
5.8
作者：
Li, Heng
通讯作者：
Li, Heng
影响因子：
5.8
作者：
Behr, Aaron A.;Liu, Katherine Z.;Ramachandran, Sohini
通讯作者：
Ramachandran, Sohini
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
影响因子：
5.3
作者：
Sloan-Heggen CM;Bierer AO;Shearer AE;Kolbe DL;Nishimura CJ;Frees KL;Ephraim SS;Shibata SB;Booth KT;Campbell CA;Ranum PT;Weaver AE;Black-Ziegelbein EA;Wang D;Azaiez H;Smith RJH
通讯作者：
Smith RJH