Genetic variations and haplotype diversity of the UGT1 gene cluster in the Chinese population.
Genetic variations and haplotype diversity of the UGT1 gene cluster in the Chinese population.
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中国人群UGT1基因簇遗传变异及单倍型多样性
DOI：
10.1371/journal.pone.0033988
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wu Q
中科院分区：
文献类型：
--
作者：
Yang J;Cai L;Huang H;Liu B;Wu Q
脊椎动物需要巨大的分子多样性来抵御许多小的疏水化学物质。UDP-葡萄糖醛酸基转移酶（UGT）是一个大家族的解毒酶，其葡萄糖醛酸化外源性物质和内生性物质，促进它们从体内排泄。UGT 1基因簇包含可变的第一外显子的串联阵列，每个外显子之前有一个特定的启动子，和一组常见的下游恒定外显子，类似于原钙粘蛋白（Pcdh），免疫球蛋白和T细胞受体基因簇的基因组组织。为了协助中国人的药物基因组学研究，我们对253名无关中国人的UGT 1基因簇的9个第一外显子、启动子和内含子区域以及5个共同外显子进行了测序。我们发现了101个多态性，并发现了15个新的SNPs。然后，我们计算每个多态性的等位基因频率，并重建其连锁不平衡（LD）图。UGT 1基因簇可分为5个连锁区：Block 9（UGT 1A 9）、Block 9/7/6（UGT 1A 9、UGT 1A 7和UGT 1A 6）、Block 5（UGT 1A 5）、Block 4/3（UGT 1A 4和UGT 1A 3）和Block 3′ UTR。此外，我们推断单倍型和选择其tagSNPs。最后，将我们的数据与HapMap项目的其他三个群体的数据进行比较，揭示了中国人UGT 1遗传多样性的种族特异性。这些发现对未来UGT 1基因簇的分子遗传学研究以及中国人的个体化药物治疗具有重要意义。
Vertebrates require tremendous molecular diversity to defend against numerous small hydrophobic chemicals. UDP-glucuronosyltransferases (UGTs) are a large family of detoxification enzymes that glucuronidate xenobiotics and endobiotics, facilitating their excretion from the body. The UGT1 gene cluster contains a tandem array of variable first exons, each preceded by a specific promoter, and a common set of downstream constant exons, similar to the genomic organization of the protocadherin (Pcdh), immunoglobulin, and T-cell receptor gene clusters. To assist pharmacogenomics studies in Chinese, we sequenced nine first exons, promoter and intronic regions, and five common exons of the UGT1 gene cluster in a population sample of 253 unrelated Chinese individuals. We identified 101 polymorphisms and found 15 novel SNPs. We then computed allele frequencies for each polymorphism and reconstructed their linkage disequilibrium (LD) map. The UGT1 cluster can be divided into five linkage blocks: Block 9 (UGT1A9), Block 9/7/6 (UGT1A9, UGT1A7, and UGT1A6), Block 5 (UGT1A5), Block 4/3 (UGT1A4 and UGT1A3), and Block 3′ UTR. Furthermore, we inferred haplotypes and selected their tagSNPs. Finally, comparing our data with those of three other populations of the HapMap project revealed ethnic specificity of the UGT1 genetic diversity in Chinese. These findings have important implications for future molecular genetic studies of the UGT1 gene cluster as well as for personalized medical therapies in Chinese.
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斑马鱼 Ugt 库的克隆和比较分析揭示了其进化多样性
影响因子：
3.7
作者：
Huang H;Wu Q
通讯作者：
Wu Q
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
DOI：
10.1097/00008571-200008000-00007
发表时间：
2000-08-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Huang, CS;Luo, GA;Yang, SS
通讯作者：
Yang, SS
影响因子：
1.8
作者：
Locuson, C. W.;Tracy, T. S.
通讯作者：
Tracy, T. S.
多变量外显子的适应性演变和药物代谢酶的结构多样性。
影响因子：
3.4
作者：
Li, Can;Wu, Qiang
通讯作者：
Wu, Qiang