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Gene-Based Single Nucleotide Polymorphisms and Linkage Disequilibrium Patterns of 29 Asthma Candidate Genes in the Chromosome 5q31–33 Region in Koreans

Ryu H.-J.a · Jung H.-Y.a · Park J.-S.a · Ryu G.-M.a · Heo J.Y.a · Kim J.-J.a · Moon S.-M.a · Kim H.-T.a · Lee J.-Y.a · Koh I.a · Kim J.-W.a · Rho J.K.a · Han B.-G.a · Kim H.b · Park C.-S.c · Oh B.a · Park C.a · Lee J.-K.a · Kimm K.a
aNational Genome Research Institute, National Institute of Health, bMacrogen Co., Seoul, and cGenome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Hospital, Gyeonggi-Do, Korea Int Arch Allergy Immunol 2006;139:209–216 (DOI:10.1159/000091166)

Abstract

Background and Methods: Numerous genetic studies have mapped asthma susceptibility genes to a region on chromosome 5q31–33 in several populations. This region contains a cluster of cytokines and other immune-related genes important in immune response. In the present study, to determine the genetic variations and patterns of linkage disequilibrium (LD), we resequenced all the exons and promoter regions of the 29 asthma candidate genes in the chromosome 5q31–33 region. Results: We identified a total of 314 genetic variants, including 289 single nucleotide polymorphisms (SNPs), 22 insertion/deletion polymorphisms and 3 microsatellites. Standardized variance data for allele frequency revealed substantial differences in SNP allele frequencies among different ethnic groups. Interestingly, significant ethnic differences were observed mainly in intron SNPs. LD block analysis using 174 common SNPs with a frequency of >10% disclosed strong LD within most candidate genes. No significant LD was observed across genes, except for one LD block (CD14-IK block). Gene-based haplotype analyses showed that 1–5 haplotype-tagging SNPs may be used to define the six or fewer common haplotypes with a frequency of >5%, regardless of the number of SNPs. Conclusion: Overall, our results provide useful information for the identification of immune-mediated disease genes in the chromosome 5q31–33 region, as well as valuable evidence for gene-based haplotype analysis in disease association studies.

 

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