A detailed genetic map of the chromosome 7 bronchial hyper-responsiveness locus

被引:13
作者
Leaves, NI [1 ]
Bhattacharyya, S [1 ]
Wiltshire, S [1 ]
Cookson, WOCM [1 ]
机构
[1] Univ Oxford, Wellcome Trust Ctr Human Genet, Asthma Genet Grp, Oxford OX3 7BN, England
关键词
bronchial responsiveness; genetic map; chromosome; 7; parent of origin effects;
D O I
10.1038/sj.ejhg.5200787
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Non-specific bronchial hyper-responsiveness to various inhaled stimuli is a characteristic of asthma. We have previously shown linkage of bronchial responsiveness to methacholine (measured as dose-response slope (DRS)) and the peripheral blood eosinophil count (EOS) to chromosome 7. We have now further investigated these linkages by genotyping 49 microsatellite markers across the DRS locus on chromosome 7. The markers were spaced on average 2.6 cM apart and spanned a sex averaged cumulative genetic distance of 129 cM. Multipoint linkage to DRS was bimodal and dipped at the centromere. The two peaks of linkage were close to markers D7S484 (P=0.0003) and D7S669 (P=0.006) respectively. Separate testing for linkage to paternally and maternally derived alleles showed that the linkage near D7S484 was paternally derived (P<0.00001): maternally derived alleles did not exhibit significant linkage. The results indicate that two disparate loci may be influencing asthma from chromosome 7.
引用
收藏
页码:177 / 182
页数:6
相关论文
共 38 条
[1]   Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases [J].
Becker, KG ;
Simon, RM ;
Bailey-Wilson, JE ;
Freidlin, B ;
Biddison, WE ;
McFarland, HF ;
Trent, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (17) :9979-9984
[2]   Bronchial elastic fibers in normal subjects and asthmatic patients [J].
Bousquet, J ;
Lacoste, JY ;
Chanez, P ;
Vic, P ;
Godard, P ;
Michel, FB .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1996, 153 (05) :1648-1654
[3]  
BRITTON J, 1988, EUR RESPIR J, V1, P478
[4]   Comprehensive human genetic maps: Individual and sex-specific variation in recombination [J].
Broman, KW ;
Murray, JC ;
Sheffield, VC ;
White, RL ;
Weber, JL .
AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 63 (03) :861-869
[5]  
*CAS W RES U DEP E, 1997, SAGE STAT AN GEN EP
[6]   The alliance of genes and environment in asthma and allergy [J].
Cookson, W .
NATURE, 1999, 402 (6760) :B5-B11
[7]   RELATIVE RISKS OF BRONCHIAL HYPERRESPONSIVENESS ASSOCIATED WITH SKIN-PRICK TEST RESPONSES TO COMMON ANTIGENS IN YOUNG-ADULTS [J].
COOKSON, WOCM ;
DEKLERK, NH ;
RYAN, GR ;
JAMES, AL ;
MUSK, AW .
CLINICAL AND EXPERIMENTAL ALLERGY, 1991, 21 (04) :473-479
[8]   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
[9]   QUANTITATIVE LOCUS ANALYSIS OF AIRWAY HYPERRESPONSIVENESS IN A/J AND C57BL/6J MICE [J].
DESANCTIS, GT ;
MERCHANT, M ;
BEIER, DR ;
DREDGE, RD ;
GROBHOLZ, JK ;
MARTIN, TR ;
LANDER, ES ;
DRAZEN, JM .
NATURE GENETICS, 1995, 11 (02) :150-154
[10]   A comprehensive genetic map of the human genome based on 5,264 microsatellites [J].
Dib, C ;
Faure, S ;
Fizames, C ;
Samson, D ;
Drouot, N ;
Vignal, A ;
Millasseau, P ;
Marc, S ;
Hazan, J ;
Seboun, E ;
Lathrop, M ;
Gyapay, G ;
Morissette, J ;
Weissenbach, J .
NATURE, 1996, 380 (6570) :152-154