Strong linkage disequilibrium at the nucleotide analogue transporter ABCC5 gene locus
Strong linkage disequilibrium at the nucleotide analogue transporter ABCC5 gene locus
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DOI：
10.1097/01213011-200502000-00005
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发表时间：
2005-02-01
影响因子：
2.6
通讯作者：
Lee, CGL
中科院分区：
文献类型：
--
作者：
Gwee, PC;Tang, K;Lee, CGL
ABCC5转运蛋白是一种普遍表达的依赖于ATP的外排泵，可输出核苷酸类似物，包括硫代嘌呤抗癌药物和抗病毒药物。该基因的多态可能与不同个体对这些药物的反应不同有关。单倍型作图有助于在关联研究中识别因果遗传变异。在这里，我们报告了ABCC5基因全长100kb的单倍型和连锁不平衡(LD)特征在五个种族独特的群体中的特征。在检测的24个单核苷酸多态(SNPs)中，有16个在所有5个群体中出现频率较高，并用于进一步的单倍型和LD分析。ABCC5基因在所有群体中都存在很强的LD，半长LD(LD0.5)估计在106-293kb之间，有用的LD超过100kb。在四个非非洲群体中观察到的单倍型多样性很低，在经历了最大重组的模拟群体中，观察到的单倍型总数不到预测的单倍型数量的22%。在非非洲人和非裔美国人中分别发现了4个和6个标签SNPs，约占观察到的单倍型的90%。(C)2005年，Lippincott Williams&Wilkins。
The ABCC5 transporter is a ubiquitously expressed ATP-dependent efflux pump that exports nucleotide analogues, including thiopurine anticancer drugs and antiviral drugs. Polymorphisms within this gene may be associated with differences in response to these drugs between different individuals. Haplotype mapping may facilitate the identification of causal genetic variations in association studies. Here, we report the characterization of the haplotype and linkage disequilibrium (LD) profiles across the entire 100 kb of the ABCC5 gene in five ethnically unique populations. Of 24 single nucleotide polymorphisms (SNPs) examined, 16 were observed to occur at high frequency in all five populations and were used for further haplotype and LD analyses. The ABCC5 gene was found to be in strong LD in all populations with half-length LD (LD0.5) estimated to be between 106 and 293 kb long and useful LD extending beyond 100 kb. Low haplotype diversity was observed in the four non-African populations, where the total number of observed haplotypes constituted less than 22% of the predicted number of haplotypes in a simulated population that has undergone maximum recombination. Four and six tagging SNPs, which could account for approximately 90% of observed haplotypes, were identified in the non-African and African-American populations, respectively. (c) 2005 Lippincott Williams & Wilkins.