Major quantitative trait locus for eosinophil count is located on chromosome 2q

被引:26
作者
Evans, DM
Zhu, G
Duffy, DL
Montgomery, GW
Frazer, IH
Martin, NG
机构
[1] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England
[2] Univ Queensland, Queensland Inst Med Res, Brisbane, Qld, Australia
[3] Univ Queensland, Joint Genet Program, Brisbane, Qld, Australia
[4] Univ Queensland, Princess Alexandra Hosp, Ctr Immunol & Canc Res, Brisbane, Qld, Australia
关键词
eosinophils; asthma; genetics; linkage; QTL; twins;
D O I
10.1016/j.jaci.2004.05.060
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Eosinophils are granulocytic white blood cells implicated in asthma and atopic disease. The degree of eosinophilia in the blood of patients with asthma correlates with the severity of asthmatic symptoms. Quantitative trait loci (QTL) linkage analysis of eosinophil count may be a more powerful strategy of mapping genes involved in asthma than linkage analysis using affected relative pairs. 1 Objective: To identify QTLs responsible for variation in eosinophil count in adolescent twins. Methods: We measured eosinophil count longitudinally in 738 pairs of twins at 12, 14, and 16 years of age. We typed 757 highly polymorphic microsatellite markers at an average spacing of similar to5 centimorgans across the genome. We then used multipoint variance components linkage analysis to test for linkage between marker loci and eosinophil concentrations at each age across the genome. Results: We found highly significant linkage on chromosome 2q33 in 12-year-old twins (logarithm of the odds = 4.6; P = .000002) and suggestive evidence of linkage in the same region in 14-year-olds (logarithm of the odds = 1.0; P = .016). We also found suggestive evidence of linkage at other areas of the genome, including regions on chromosomes 2, 3, 4, 8, 9, 11, 12, 17, 20, and 22. Conclusion: A QTL for eosinophil count is present on chromosome 2q33. This QTL might represent a gene involved in asthma pathophysiology.
引用
收藏
页码:826 / 830
页数:5
相关论文
共 36 条
[1]   Merlin-rapid analysis of dense genetic maps using sparse gene flow trees [J].
Abecasis, GR ;
Cherny, SS ;
Cookson, WO ;
Cardon, LR .
NATURE GENETICS, 2002, 30 (01) :97-101
[2]  
Aitken JF, 1996, CANCER, V78, P252, DOI 10.1002/(SICI)1097-0142(19960715)78:2<252::AID-CNCR10>3.0.CO
[3]  
2-V
[4]   Multipoint quantitative-trait linkage analysis in general pedigrees [J].
Almasy, L ;
Blangero, J .
AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 62 (05) :1198-1211
[5]  
AMOS CI, 1994, AM J HUM GENET, V54, P535
[6]  
BLACKWELDER W C, 1985, Genetic Epidemiology, V2, P85, DOI 10.1002/gepi.1370020109
[7]   A genome-wide search for quantitative trait loci underlying asthma [J].
Daniels, SE ;
Bhattacharrya, S ;
James, A ;
Leaves, NI ;
Young, A ;
Hill, MR ;
Faux, JA ;
Ryan, GF ;
leSouef, PN ;
Lathrop, GM ;
Musk, AW ;
Cookson, WOCM .
NATURE, 1996, 383 (6597) :247-250
[8]   Genome screen for asthma and related phenotypes in the French EGEA study [J].
Dizier, MH ;
Besse-Schmittler, C ;
Guilloud-Bataille, M ;
Annesi-Maesano, I ;
Boussaha, M ;
Bousquet, J ;
Charpin, D ;
Degioanni, A ;
Gormand, F ;
Grimfeld, A ;
Hochez, J ;
Hyne, G ;
Lockhart, A ;
Luillier-Lacombe, M ;
Matran, R ;
Meunier, F ;
Neukirch, F ;
Pacheco, Y ;
Parent, V ;
Paty, E ;
Pin, I ;
Pison, C ;
Scheinmann, P ;
Thobie, N ;
Vervloet, D ;
Kauffmann, F ;
Feingold, J ;
Lathrop, M ;
Demenais, F .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2000, 162 (05) :1812-1818
[9]   EOSINOPHILS, BRONCHIAL HYPERREACTIVITY AND LATE-PHASE ASTHMATIC REACTIONS [J].
DURHAM, SR ;
KAY, AB .
CLINICAL ALLERGY, 1985, 15 (05) :411-418
[10]   Multivariate multipoint linkage analysis of quantitative trait loci [J].
Eaves, LJ ;
Neale, MC ;
Maes, H .
BEHAVIOR GENETICS, 1996, 26 (05) :519-525