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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.

Original publication

DOI

10.1038/sj.gene.6364008

Type

Journal article

Journal

Genes and immunity

Publication Date

10/2003

Volume

4

Pages

476 - 486

Addresses

Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, UK. ackerman@fas.harvard.edu

Keywords

Humans, Genetic Predisposition to Disease, Tumor Necrosis Factor-alpha, Genetic Markers, Genetics, Population, Major Histocompatibility Complex, Gene Frequency, Genotype, Haplotypes, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Alleles, Entropy, Adult, Gambia, Female, Male