Immune diversity sheds light on missing variation in worldwide genetic diversity panels.
Immune diversity sheds light on missing variation in worldwide genetic diversity panels.
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DOI：
10.1371/journal.pone.0206512
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Paganini J
中科院分区：
文献类型：
--
作者：
Abi-Rached L;Gouret P;Yeh JH;Di Cristofaro J;Pontarotti P;Picard C;Paganini J
定义全球人类遗传变异是揭示基因组可塑性如何导致疾病的关键一步。然而，目前还没有衡量标准来评估目前广泛使用的遗传变异数据的代表性和完整性。我们在这里表明，人类白细胞抗原（HLA）基因可以作为这样的指标，因为它们都是最多态性和研究最多的遗传系统。作为一个测试案例，我们调查了1,000个基因组项目小组。使用高准确度的计算机HLA分型，我们发现超过20%的常见HLA变体和超过70%的罕见HLA变体在这个全球遗传变异的参考面板中缺失，这是由于采样不足和地理覆盖不完整，特别是在大洋洲和西亚。由于常见和罕见的变异都有助于疾病，因此这项研究说明了HLA多样性如何检测和帮助修复不完整的采样，从而加速努力全面概述与健康和疾病相关的遗传变异。
Defining worldwide human genetic variation is a critical step to reveal how genome plasticity contributes to disease. Yet, there is currently no metric to assess the representativeness and completeness of current and widely used data on genetic variation. We show here that Human Leukocyte Antigen (HLA) genes can serve as such metric as they are both the most polymorphic and the most studied genetic system. As a test case, we investigated the 1,000 Genomes Project panel. Using high-accuracy in silico HLA typing, we find that over 20% of the common HLA variants and over 70% of the rare HLA variants are missing in this reference panel for worldwide genetic variation, due to undersampling and incomplete geographical coverage, in particular in Oceania and West Asia. Because common and rare variants both contribute to disease, this study thus illustrates how HLA diversity can detect and help fix incomplete sampling and hence accelerate efforts to draw a comprehensive overview of the genetic variation that is relevant to health and disease.
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影响因子：
64.8
作者：
Mallick, Swapan;Li, Heng;Lipson, Mark;Mathieson, Iain;Gymrek, Melissa;Racimo, Fernando;Zhao, Mengyao;Chennagiri, Niru;Nordenfelt, Susanne;Tandon, Arti;Skoglund, Pontus;Lazaridis, Iosif;Sankararaman, Sriram;Fu, Qiaomei;Rohland, Nadin;Renaud, Gabriel;Erlich, Yaniv;Willems, Thomas;Gallo, Carla;Spence, Jeffrey P.;Song, Yun S.;Poletti, Giovanni;Balloux, Francois;van Driem, George;de Knijff, Peter;Romero, Irene Gallego;Jha, Aashish R.;Behar, Doron M.;Bravi, Claudio M.;Capelli, Cristian;Hervig, Tor;Moreno-Estrada, Andres;Posukh, Olga L.;Balanovska, Elena;Balanovsky, Oleg;Karachanak-Yankova, Sena;Sahakyan, Hovhannes;Toncheva, Draga;Yepiskoposyan, Levon;Tyler-Smith, Chris;Xue, Yali;Abdullah, M. Syafiq;Ruiz-Linares, Andres;Beall, Cynthia M.;Di Rienzo, Anna;Jeong, Choongwon;Starikovskaya, Elena B.;Metspalu, Ene;Parik, Juri;Villems, Richard;Henn, Brenna M.;Hodoglugil, Ugur;Mahley, Robert;Sajantila, Antti;Stamatoyannopoulos, George;Wee, Joseph T. S.;Khusainova, Rita;Khusnutdinova, Elza;Litvinov, Sergey;Ayodo, George;Comas, David;Hammer, Michael F.;Kivisild, Toomas;Klitz, William;Winkler, Cheryl A.;Labuda, Damian;Bamshad, Michael;Jorde, Lynn B.;Tishkoff, Sarah A.;Watkins, W. Scott;Metspalu, Mait;Dryomov, Stanislav;Sukernik, Rem;Singh, Lalji;Thangaraj, Kumarasamy;Paeaebo, Svante;Kelso, Janet;Patterson, Nick;Reich, David
通讯作者：
Reich, David
影响因子：
64.8
作者：
Li X;Kim Y;Tsang EK;Davis JR;Damani FN;Chiang C;Hess GT;Zappala Z;Strober BJ;Scott AJ;Li A;Ganna A;Bassik MC;Merker JD;GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Hall IM;Battle A;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
82.9
作者：
Scott DA;Zhang F
通讯作者：
Zhang F
影响因子：
14.9
作者：
Gonzalez-Galarza FF;Christmas S;Middleton D;Jones AR
通讯作者：
Jones AR
影响因子：
3.7
作者：
Gourraud PA;Khankhanian P;Cereb N;Yang SY;Feolo M;Maiers M;Rioux JD;Hauser S;Oksenberg J
通讯作者：
Oksenberg J