Haplotype structure of inflammatory cytokines genes (IL1B, IL6 and TNF/LTA) in US Caucasians and African Americans
Haplotype structure of inflammatory cytokines genes (IL1B, IL6 and TNF/LTA) in US Caucasians and African Americans
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DOI：
10.1038/sj.gene.6364118
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发表时间：
2004-09-01
影响因子：
5
通讯作者：
Goldman, D
中科院分区：
文献类型：
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作者：
Belfer, I;Buzas, B;Goldman, D
主要的炎症细胞因子白介素（IL）1 β、IL6和肿瘤坏死因子（TNFalpha）在感染、炎症和应激反应中起着至关重要的作用。此前，对三个编码基因进行了重新测序，确定了在神经退行性疾病、代谢紊乱和癌症的关联研究中使用的启动子多态性。这些研究产生了有趣但不一致的结果，可能是因为已知的功能变体：il1b - 511c >t, IL6-174 G>C和TNF-308 G>A提供了这些基因总功能多样性的不完整图像。因此，我们创建了IL1B， IL6和TNF/LTA的标记面板，其中包括已知的功能标记，但也包括其他均匀间隔和足够密度的标记，以识别单倍型块结构并最大限度地提高单倍型多样性。在96名美国白种人和96名非洲裔美国人中，共有26个标记进行了基因分型。在这两个人群中，在IL1B， IL6和TNF/LTA中观察到单个块，几乎没有历史重组的证据。对于每个基因，单倍型捕获了每个功能位点的信息内容，即使该位点没有基因分型，单倍型可能会捕获来自等位基因丰度适中的未知功能位点的信号。本研究证明了使用基因单倍型图谱和标记面板作为相关表型连锁研究工具的实用性。
The major inflammatory cytokines interleukin( IL)1beta, IL6 and tumor necrosis factor alpha (TNFalpha) play a crucial role in infection, inflammation and stress responses. Previously, three coding genes were resequenced, identifying promoter polymorphisms that were used in association studies of neurodegenerative diseases, metabolic disorders and cancer. These studies have produced intriguing but inconsistent results, potentially because the known functional variants: IL1B-511 C>T, IL6-174 G>C and TNF-308 G>A provided an incomplete picture of the total functional diversity at these genes. Therefore, we created marker panels for IL1B, IL6 and TNF/LTA that included the known functional marker but also other markers evenly spaced and with sufficient density to identify haplotype block structure and to maximize haplotype diversity. A total of 26 markers were genotyped in 96 US Caucasians and 96 African Americans. In both populations, a single block with little evidence of historical recombination was observed in IL1B, IL6 and TNF/LTA. For each gene, haplotypes captured the information content of each functional locus, even if that locus was not genotyped, and presumably haplotypes would capture the signal from unknown functional loci whose alleles are of moderate abundance. This study demonstrates the utility of using gene haplotype maps and marker panels as tools for linkage studies on related phenotypes.