Complex haplotypic structure of the central MHC region flanking TNF in a West African population
Complex haplotypic structure of the central MHC region flanking TNF in a West African population
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DOI：
10.1038/sj.gene.6364008
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发表时间：
2003-10-01
影响因子：
5
通讯作者：
Kwiatkowski, DP
中科院分区：
文献类型：
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作者：
Ackerman, HC;Ribas, G;Kwiatkowski, DP
TNF多态性与疟疾和其他感染性和炎症性疾病的易感性有关。我们调查了150个西非染色体的样本，以确定25个SNP标记之间的连锁不平衡（LD）位于80 kb的片段的MHC III类区域，包括TNF和8个相邻的基因。我们观察到45个单倍型，其中22个占样本的80%。LD的模式是明显不规则的，使得许多标记物与相邻标记物不显示LD，但与远得多的标记物显示高LD。我们介绍了一种方法，检查LD数据的疾病关联研究的样本量的考虑的基础上的影响：这表明，某些TNF多态性可能会产生积极的协会，如果真正的疾病等位基因居住在LTA或BAT 1。我们的结论是，需要详细的标记地图，以解决在TNF位点观察到的疾病关联的因果起源。
TNF polymorphisms have been associated with susceptibility to malaria and other infectious and inflammatory conditions. We investigated a sample of 150 West African chromosomes to determine linkage disequilibrium (LD) between 25 SNP markers located in an 80 kb segment of the MHC Class III region encompassing TNF and eight neighbouring genes. We observed 45 haplotypes, and 22 of them comprise 80% of the sample. The pattern of LD is remarkably patchy, such that many markers show no LD with adjacent markers but high LD with markers that are much further away. We introduce a method of examining the implications of LD data for disease association studies based on sample size considerations: this shows that certain TNF polymorphisms would be likely to yield positive associations if the true disease allele resided in LTA or BAT1. We conclude that detailed marker maps are needed to resolve the causal origin of disease associations observed at the TNF locus.