Large-scale identification and characterization of genetic variants in asthma candidate genes.
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 x 10(-4)-14.53 x 10(-4)), but the average nucleotide diversity between coding SNPs (cSNPs) and noncoding SNPs was roughly equivalent (4.63 x 10(-4) vs 4.69 x 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 x 10(-4) vs 3.14 x 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.
Kim
Jae-Jung
JJ
National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Gu, Seoul, 122-701, South Korea.
Kim
Hyun-Hee
HH
Park
Joo-Hyun
JH
Ryu
Ha-Jung
HJ
Kim
Juyoung
J
Moon
Songmean
S
Gu
Haeok
H
Kim
Hung-Tae
HT
Lee
Jong-Young
JY
Han
Bok-Ghee
BG
Park
Chan
C
Kimm
Kuchan
K
Park
Choon-Sik
CS
Lee
Jong-Keuk
JK
Oh
Bermseok
B
D001249:Asthma / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007723:Korea; D020641:Polymorphism, Single Nucleotide