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

First Author  Camateros P Year  2010
Journal  Mamm Genome Volume  21
Issue  1-2 Pages  28-38
PubMed ID  20012967 Mgi Jnum  J:156885
Mgi Id  MGI:4421624 Doi  10.1007/s00335-009-9236-z
Citation  Camateros P, et al. (2010) Identification of novel chromosomal regions associated with airway hyperresponsiveness in recombinant congenic strains of mice. Mamm Genome 21(1-2):28-38
abstractText  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 </= 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.
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