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Am J Physiol Lung Cell Mol Physiol 277: L1118-L1123, 1999;
1040-0605/99 $5.00
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Vol. 277, Issue 6, L1118-L1123, December 1999

Quantitative trait locus mapping of airway responsiveness to chromosomes 6 and 7 in inbred mice

G. T. De Sanctis1, J. B. Singer2, A. Jiao1, C. N. Yandava1, Y. H. Lee1, T. C. Haynes3, E. S. Lander2,4, D. R. Beier5, and J. M. Drazen1

1 Combined Program in Pulmonary and Critical Care Medicine and 5 Genetics Division, Brigham and Women's Hospital and Harvard Medical School, Boston 02115; 2 Whitehead Institute/ Massachusetts Institute of Technology Center for Genome Research, Whitehead Institute for Biomedical Research, Cambridge 02142; 4 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; and 3 The Jackson Laboratory, Bar Harbor, Maine 04609

Quantitative trait locus (QTL) mapping was used to identify chromosomal regions contributing to airway hyperresponsiveness in mice. Airway responsiveness to methacholine was measured in A/J and C3H/HeJ parental strains as well as in progeny derived from crosses between these strains. QTL mapping of backcross [(A/J × C3H/HeJ) × C3H/HeJ] progeny (n = 137-227 informative mice for markers tested) revealed two significant linkages to loci on chromosomes 6 and 7. The QTL on chromosome 6 confirms the previous report by others of a linkage in this region in the same genetic backgrounds; the second QTL, on chromosome 7, represents a novel locus. In addition, we obtained suggestive evidence for linkage (logarithm of odds ratio = 1.7) on chromosome 17, which lies in the same region previously identified in a cross between A/J and C57BL/6J mice. Airway responsiveness in a cross between A/J and C3H/HeJ mice is under the control of at least two major genetic loci, with evidence for a third locus that has been previously implicated in an A/J and C57BL/6J cross; this indicates that multiple genetic factors control the expression of this phenotype.

asthma; methacholine; A/J mice; C3H/HeJ mice


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