Interacting genetic loci cause airway hyperresponsiveness.
Document Type
Article
Publication Date
2005
First Page
105
Last Page
111
JAX Source
Physiol Genomics 2005 Mar; 21(1):105-11.
Abstract
Airway hyperresponsiveness (AHR) is a key physiological component of asthma, and the genetic basis of this complex trait has remained elusive. We created recombinant congenic mice with increased naive AHR by serially backcrossing A/J mice (which have elevated naive AHR) with C57BL/6J mice and selecting for mice with an elevated naive AHR phenotype. The seventh backcross-generation hyperresponsive mice retained A/J loci in three regions. Quantitative trait linkage (QTL) analysis of 123 unselected N8 progeny demonstrated that the AHR phenotype was not associated with any single locus but was significantly associated with an interaction of loci on chromosomes 2 and 6. These findings were confirmed in an independent analysis of chromosome substitution strain mice. The identification of genomic regions containing loci causally associated with AHR and the demonstration that this trait requires their interaction have important implications for the dissection of the genetic etiology of asthma in humans.
Recommended Citation
Ackerman KG,
Huang H,
Grasemann H,
Puma C,
Singer JB,
Hill AE,
Lander E,
Nadeau JH,
Churchill GA,
Drazen JM,
Beier DR.
Interacting genetic loci cause airway hyperresponsiveness. Physiol Genomics 2005 Mar; 21(1):105-11.