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Genetic Variation at the Chromosome 16 Chemokine Gene Cluster: Development of a Strategy for Association Studies in Complex Disease
Author(s) -
Fisher S. A.,
Moody A.,
Mirza M. M.,
Cuthbert A. P.,
Hampe J.,
Macpherson A.,
Sanderson J.,
Forbes A.,
Mansfield J.,
Schreiber S.,
Lewis C. M.,
Mathew C. G.
Publication year - 2003
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1046/j.1469-1809.2003.00040.x
Subject(s) - linkage disequilibrium , single nucleotide polymorphism , genetics , tag snp , locus (genetics) , biology , genetic association , snp genotyping , candidate gene , snp , dbsnp , inflammatory bowel disease , genotyping , haplotype , allele , gene , genotype , disease , medicine , pathology
Summary The chemokine gene cluster [ CCL22, CX3CL1, CCL17 ] (previously known as [ SCYA22, SCYD1, SCYA17 ]) is a candidate locus for one of the susceptibility genes for inflammatory bowel disease that are located in the peri‐centromeric region of chromosome 16. Screening for sequence variation at this locus led to the detection of 14 single nucleotide polymorphisms (SNPs). An efficient experimental and computational approach was developed to estimate allele frequencies and pairwise linkage disequilibrium relationships between SNPs at this locus, and to test them for association with inflammatory bowel disease. The 12 common SNPs were assigned to 5 distinct linkage disequilibrium groups. Genotyping of one SNP from each linkage disequilibrium group in a large cohort of families with inflammatory bowel disease did not provide convincing evidence of association with either Crohn's disease or ulcerative colitis. We describe an efficient experimental design from SNP screening to association testing. This strategy can be used to test candidate genes for involvement in susceptibility to complex disease.