Identification of novel chromosomal regions associated with airway hyperresponsiveness in recombinant congenic strains of mice

被引:16
作者
Camateros, Pierre [7 ]
Marino, Rafael [7 ]
Fortin, Anny [6 ]
Martin, James G. [5 ,7 ]
Skamene, Emil [7 ]
Sladek, Rob [3 ,4 ,7 ]
Radzioch, Danuta [1 ,2 ,7 ]
机构
[1] Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada
[2] McGill Univ, Dept Human Genet, Montreal, PQ H3A 2T5, Canada
[3] McGill Univ, Montreal, PQ H3A 1A4, Canada
[4] Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada
[5] McGill Univ, Meakins Christie Labs, Montreal, PQ H2X 2P2, Canada
[6] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada
[7] McGill Univ, Dept Med, Div Expt Med, Montreal, PQ H3A 2T5, Canada
基金
加拿大健康研究院;
关键词
QUANTITATIVE-TRAIT LOCI; SUSCEPTIBILITY LOCUS; ALLERGIC-ASTHMA; CANDIDATE GENES; SMOOTH-MUSCLE; INBRED MICE; RESPONSIVENESS; MOUSE; A/J; HYPERREACTIVITY;
D O I
10.1007/s00335-009-9236-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Airway responsiveness is the ability of the airways to respond to bronchoconstricting stimuli by reducing their diameter. Airway hyperresponsiveness has been associated with asthma susceptibility in both humans and murine models, and it has been shown to be a complex and heritable trait. In particular, the A/J mouse strain is known to have hyperresponsive airways, while the C57BL/6 strain is known to be relatively refractory to bronchoconstricting stimuli. We analyzed recombinant congenic strains (RCS) of mice generated from these hyper- and hyporesponsive parental strains to identify genetic loci underlying the trait of airway responsiveness in response to methacholine as assessed by whole-body plethysmography. Our screen identified 16 chromosomal regions significantly associated with airway hyperresponsiveness (genome-wide P a parts per thousand currency sign 0.05): 8 are supported by independent and previously published reports while 8 are entirely novel. Regions that overlap with previous reports include two regions on chromosome 2, three on chromosome 6, one on chromosome 15, and two on chromosome 17. The 8 novel regions are located on chromosome 1 (92-100 cM), chromosome 5 (> 73 cM), chromosome 7 (> 63 cM), chromosome 8 (52-67 cM), chromosome 10 (3-7 cM and > 68 cM), and chromosome 12 (25-38 cM and > 52 cM). Our data identify several likely candidate genes from the 16 regions, including Ddr2, Hc, Fbn1, Flt3, Utrn, Enpp2, and Tsc.
引用
收藏
页码:28 / 38
页数:11
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