Bhr8^A/J
QTL Variant Detail

Summary

• QTL variant: Bhr8^A/J
• Name: bronchial hyperresponsiveness 8; A/J
• MGI ID: MGI:5635628
• QTL: Bhr8 Location: Chr6:4464884-4465015 bp Genetic Position: Chr6, Syntenic

Variant origin

• Strain of Specimen: A/J

Variant description

• Allele Type: QTL

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:97472

Linkage analysis was performed on 123 recombinant congenic animals at the N8 generation to identify QTLs associated with airway hyperresponsiveness (AHR). A recombinant congenic line was created by repeated backcrossing of (C57BL/6J x A/J)F1 animals to C57BL/6J for 7 generations and selecting for the AHR phenotype at each generation. Donor strain A/J exhibits increased naive AHR compared to background strain C57BL/6J. At generation N8 the recombinant congenic line displayed 80% of the donor A/J AHR phenotype. This line retained A/J-derived donor DNA on chromosomes 2 from D2Mit259 - D2Mit148, chromosome 6 from D6Mit86 - D6Mit9, and chromosome 10 from D10Mit95 - D10Mit103.

When analyzed separately the loci on chromosomes 2 and 6 show only a suggestive linkage to AHR. The combined effect of these 2 loci when inherited together show a highly significant linkage to AHR with LOD=5.5, and explains 18.7% of the total variance. It is believed that A/J-derived alleles confer dominantly inherited susceptibility to AHR.

The chromosome 10 locus did not show evidence of linkage to AHR.

The chromosome 2 locus was identified in a previous AHR study as Bhr1 (bronchial hyperresponsiveness 1) peaking at 74 cM. In the current study Bhr1 maps to a 25 cM interval betweenD2Mit259 (80 cM) and D2Mit148 (105 cM).

The chromosome 6 locus was identified in a previous AHR study as Bhr5 (bronchial hyperresponsiveness 5) peaking at 50.5 cM. In the current study Bhr5 maps to a 36.5 cM interval between D6Mit86 (0.5 cM) and D6Mit9 (36.5 cM).

2.10.2015 Curator Note: Because Bhr5 was originally mapped in J:33778 using a (C3H/HeJ x A/J)F1 x A/J backcross which differs from the cross used here we have named this QTL, mapping to Chr 6 to a 36.5 cM interval between D6Mit86 (0.5 cM) and D6Mit9 (36.5 cM), Bhr8.

Separate mouse lines consomic for A/J-derived chromosome 2, chromosome 6, and chromosome 10 were created on a C57BL/6J genetic background. The chromosome 2 andchromosome 6 consomics exhibit elevated AHR(P<0.0001) compared to background control strain C57BL/6J. However, heteroconsomic animals for both A/J-derived chromosome 2 plus chromosome 6 exhibit the highest degree of AHR. This finding confirms the interaction between Bhr1 and Bhr8.

References

• Original: J:97472 Ackerman KG, et al., Interacting genetic loci cause airway hyperresponsiveness. Physiol Genomics. 2005 Mar 21;21(1):105-11
• All: 1 reference(s)