Home LiteratureArticle Details
PMID: 18253752 Published · ppublish English Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

A genome-wide association scan for asthma in a general Australian population.

Human genetics ·Vol. 123 ·No. 3 ·2008-04-00 ·Pages 297-306

Hui J, Oka A, James A, Palmer LJ, Musk AW, Beilby J, Inoko H

Abstract

To date, almost every chromosome has been implicated in genetic susceptibility to asthma to some degree. When compared with single nucleotide polymorphism, microsatellite markers exhibit high levels of heterozygosity and therefore provide higher statistical power in association. The objective of this study was to perform a genome-wide association study using 23,465 in-house microsatellite markers to detect asthma susceptibility regions in the Busselton population. In this study, three separate pooled DNA screenings yielded 18 markers with significantly different estimated frequencies in the three separate "case and control" pools: each pool consisting of 60 males and 60 females. These markers were evaluated by individual typing in 360 cases and 360 controls. Two markers showed significant differences between cases and controls (P = 0.001 and P = 0.003). Regions surrounding the two markers were subjected to high-density association mapping with a total of 14 additional markers. We were able to confirm and fine map the association in these two regions by typing 14 additional microsatellite markers (1805A09 (D18S0325i), P = 0.002; 1806D05 (D18S0181i), P = 0.001). Each region contains a predicted gene that showed strong associations with asthma. Further studies are underway to characterize the novel candidate asthma susceptibility genes identified in this genome-wide study.

MeSH Terms
Adult Asthma/epidemiology,genetics Australia/epidemiology Case-Control Studies Chromosome Mapping Chromosomes, Human, Pair 18/genetics Cross-Sectional Studies DNA Primers/genetics Female Follow-Up Studies Genetic Linkage/genetics Genetic Predisposition to Disease Genome, Human Genotype Health Surveys Humans Male Microsatellite Repeats/genetics Middle Aged Polymorphism, Single Nucleotide/genetics
Chemicals
DNA Primers
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hui J
Western Australian Institute for Medical Research and UWA Centre for Medical Research, B Block, QEII Medical Centre, The University of Western Australia, Nedlands, WA, 6009, Australia. jhui@cyllene.uwa.edu.au
Oka A
James A
Palmer L J
Musk A W
Beilby J
Inoko H
References (35)
35 references, click to expand
  1. Asthma phenotypes.
    Curr Opin Pulm Med. 2007 Jan;13(1):19-23 PMID: 17133120
  2. Positional cloning of a novel gene influencing asthma from chromosome 2q14.
    Nat Genet. 2003 Nov;35(3):258-63 PMID: 14566338
  3. Genome-wide linkage analyses of total serum IgE using variance components analysis in asthmatic families.
    Genet Epidemiol. 2001 Apr;20(3):340-55 PMID: 11255243
  4. Power of genome-wide linkage disequilibrium testing by using microsatellite markers.
    J Hum Genet. 2003;48(9):487-491 PMID: 12938017
  5. Association analysis using refined microsatellite markers localizes a susceptibility locus for psoriasis vulgaris within a 111 kb segment telomeric to the HLA-C gene.
    Hum Mol Genet. 1999 Nov;8(12):2165-70 PMID: 10545595
  6. Genetic association analysis using microsatellite markers in atopic dermatitis.
    Tokai J Exp Clin Med. 2002 Aug;27(2):51-6 PMID: 12472170
  7. Toward a comprehensive set of asthma susceptibility genes.
    Annu Rev Med. 2007;58:171-84 PMID: 16907639
  8. Association mapping of disease loci, by use of a pooled DNA genomic screen.
    Am J Hum Genet. 1997 Sep;61(3):734-47 PMID: 9326338
  9. Positional identification of an asthma susceptibility gene on human chromosome 5q33.
    Am J Respir Crit Care Med. 2005 Jul 15;172(2):183-8 PMID: 15879417
  10. Simple sequence repeats as advantageous mutators in evolution.
    Trends Genet. 2006 May;22(5):253-9 PMID: 16567018
  11. Prevalence of asthma in adults in Busselton, Western Australia.
    BMJ. 1992 Nov 28;305(6865):1326-9 PMID: 1483077
  12. Fine localization of a major disease-susceptibility locus for diffuse panbronchiolitis.
    Am J Hum Genet. 2000 Feb;66(2):501-7 PMID: 10677310
  13. Comprehensive testing of positionally cloned asthma genes in two populations.
    Am J Respir Crit Care Med. 2007 Nov 1;176(9):849-57 PMID: 17702965
  14. Positive association to IgE levels and a physical map of the 13q14 atopy locus.
    Eur J Hum Genet. 2002 Apr;10(4):266-70 PMID: 12032735
  15. CGG repeat length correlates with age of onset of motor signs of the fragile X-associated tremor/ataxia syndrome (FXTAS).
    Am J Med Genet B Neuropsychiatr Genet. 2007 Jun 5;144B(4):566-9 PMID: 17427188
  16. Genetics and diagnostic refinement.
    Behav Genet. 2007 May;37(3):535-45 PMID: 17160700
  17. Effect of CAG repeat length on psychiatric disorders in Huntington's disease.
    J Psychiatr Res. 2008 Jun;42(7):544-9 PMID: 17610899
  18. Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma.
    Nat Genet. 2003 Jun;34(2):181-6 PMID: 12754510
  19. ADAM33: where are we now?
    Am J Respir Cell Mol Biol. 2004 Jul;31(1):1-2 PMID: 15208095
  20. Genomewide association analysis of human narcolepsy and a new resistance gene.
    Am J Hum Genet. 2006 Aug;79(2):252-63 PMID: 16826516
  21. Identifying novel genes contributing to asthma pathogenesis.
    Curr Opin Allergy Clin Immunol. 2007 Feb;7(1):69-74 PMID: 17218814
  22. A simple and accurate method for determination of microsatellite total allele content differences between DNA pools.
    Hum Genet. 2000 Feb;106(2):218-26 PMID: 10746564
  23. The distribution of human genetic diversity: a comparison of mitochondrial, autosomal, and Y-chromosome data.
    Am J Hum Genet. 2000 Mar;66(3):979-88 PMID: 10712212
  24. Linkage disequilibrium patterns vary substantially among populations.
    Eur J Hum Genet. 2005 May;13(5):677-86 PMID: 15657612
  25. Evidence for suppressed activity of the transcription factor NFAT1 at its proximal binding element P0 in the IL-4 promoter associated with enhanced IL-4 gene transcription in T cells of atopic patients.
    Int Immunol. 1999 Feb;11(2):297-306 PMID: 10069428
  26. Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness.
    Nature. 2002 Jul 25;418(6896):426-30 PMID: 12110844
  27. Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21.
    Am J Hum Genet. 2005 Feb;76(2):349-57 PMID: 15611928
  28. Spinocerebellar ataxia 17 (SCA17) and Huntington's disease-like 4 (HDL4).
    Cerebellum. 2008;7(2):170-8 PMID: 18418687
  29. Whole genome association study of rheumatoid arthritis using 27 039 microsatellites.
    Hum Mol Genet. 2005 Aug 15;14(16):2305-21 PMID: 16000323
  30. Alleles of RUNX2/CBFA1 gene are associated with differences in bone mineral density and risk of fracture.
    J Bone Miner Res. 2002 Aug;17(8):1527-34 PMID: 12162506
  31. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma.
    Nature. 2007 Jul 26;448(7152):470-3 PMID: 17611496
  32. A genome-wide scan of pulmonary function measures in the National Heart, Lung, and Blood Institute Family Heart Study.
    Am J Respir Crit Care Med. 2003 Jun 1;167(11):1528-33 PMID: 12637344
  33. The critical region for Behçet disease in the human major histocompatibility complex is reduced to a 46-kb segment centromeric of HLA-B, by association analysis using refined microsatellite mapping.
    Am J Hum Genet. 1999 May;64(5):1406-10 PMID: 10205273
  34. Replicating genotype-phenotype associations.
    Nature. 2007 Jun 7;447(7145):655-60 PMID: 17554299
  35. Susceptibility locus for non-obstructive azoospermia is localized within the HLA-DR/DQ subregion: primary role of DQB1*0604.
    Tissue Antigens. 2002 Jul;60(1):53-63 PMID: 12366783
Article Info
Journal
Human genetics
Abbr.
Hum Genet
ISSN
1432-1203
Published
2008-04-00
Epub
2008-00-06
Pages
297-306
Language
English
Region
Germany
NLM ID
7613873
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com