Large-scale identification and characterization of genetic variants in asthma candidate genes |
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Authors: | Jae-Jung Kim Hyun-Hee Kim Joo-Hyun Park Ha-Jung Ryu JuYoung Kim Songmean Moon Haeok Gu Hung-Tae Kim Jong-Young Lee Bok-Ghee Han Chan Park Kuchan Kimm Choon-Sik Park Jong-Keuk Lee Bermseok Oh |
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Institution: | (1) National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Gu, Seoul, 122-701, South Korea;(2) Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Hospital, 1174 Jung-Dong, Wonmi-Gu, Bucheon, Gyeonggi-Do, 420-021, South Korea |
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Abstract: | Asthma is a chronic inflammatory disorder of the airways, and a number of genetic loci are associated with the disease. Candidate
gene association studies have been regarded as effective tools to study complex traits. Knowledge of the sequence variation
and structure of the candidate genes is required for association studies. Thus, we investigated the genetic variants of 32
asthma candidate genes selected by colocalization of positional and functional candidate genes. We screened all exons and
promoter regions of those genes using 12 healthy individuals and 12 asthma patients and identified a total of 418 single nucleotide
polymorphisms (SNPs), including 270 known SNPs and 148 novel SNPs. Levels of nucleotide diversity varied from gene to gene
(0.72×10−4–14.53×10−4), but the average nucleotide diversity between coding SNPs (cSNPs) and noncoding SNPs was roughly equivalent (4.63×10−4 vs 4.69×10−4). However, nucleotide diversity of cSNPs was strongly correlated to codon degeneracy. Nucleotide diversity was much higher
at fourfold degenerate sites than at nondegenerate sites (9.42×10−4 vs 3.14×10−4). Gene-based haplotype analysis of asthma-associated genes in this study revealed that common haplotypes (frequency >5%)
represented 90.5% of chromosomes, and they could be uniquely identified with five or fewer haplotype-tagging SNPs per gene.
Therefore, our results may have important implications for the selection of asthma candidate genes and SNP markers for comprehensive
association studies using large sample populations. |
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Keywords: | Asthma Candidate gene Single nucleotide polymorphism (SNP) Haplotype Korean |
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