Gene-based single nucleotide polymorphisms and linkage disequilibrium patterns of 29 asthma candidate genes in the chromosome 5q31-33 region in Koreans.
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.


CONCLUSIONS
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.
Ryu
Ha-Jung
HJ
National Genome Research Institute, National Institute of Health, Seoul, and Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Hospital, Gyeonggi-Do, Korea.
Jung
Ho-Youl
HY
Park
Jung-Sun
JS
Ryu
Gil-Mi
GM
Heo
Jee Yeon
JY
Kim
Jae-Jung
JJ
Moon
Song-Mean
SM
Kim
Hung-Tae
HT
Lee
Jong-Young
JY
Koh
Insong
I
Kim
Jun-Woo
JW
Rho
Jae Kyun
JK
Han
Bok-Ghee
BG
Kim
Hyungtae
H
Park
Choon-Sik
CS
Oh
Bermseok
B
Park
Chan
C
Lee
Jong-Keuk
JK
Kimm
Kuchan
K
D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics* / Q000276:immunology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics / Q000276:immunology; D006801:Humans; D007723:Korea; D015810:Linkage Disequilibrium; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D017422:Sequence Analysis, DNA
D004247:DNA