Bhr1 QTL Detail

Summary

• Symbol
  Bhr1
• Name
  bronchial hyperresponsiveness 1

• Feature Type
  QTL
• IDs
  MGI:104739
  NCBI Gene: 112233
• Candidate Genes
  1 Gene

Location &
Maps

• Sequence Map
  Chr2:142593476-178442452 bp

  From MGI annotation of GRCm39
  

• View this region in JBrowse
  

• Genome Browsers
  Ensembl | UCSC | NCBI

• Genetic Map
  Chromosome 2, cM position of peak correlated region/marker: Syntenic
• QTL Archive
  Ackerman1 download
• Mapping Data
  3 experiments

Mutations,
Alleles, and
Phenotypes

• Phenotype Summary
  2 phenotypes from multigenic genotypes
  2 phenotype references
  

• All Mutations and Alleles
  2
• QTL
  2
• Incidental Mutations
  APF
• Find Mice (IMSR)
  2 strains or lines available

Sequences &
Gene Models

• NCBI Gene
  112233

Other
Accession IDs

MGD-MRK-27102

References

• Summaries
  All 4

  Phenotypes 2
• Earliest
  J:29231 De Sanctis GT, et al., Quantitative locus analysis of airway hyperresponsiveness in A/J and C57BL/6J mice. Nat Genet. 1995 Oct;11(2):150-4
• Latest
  J:97472 Ackerman KG, et al., Interacting genetic loci cause airway hyperresponsiveness. Physiol Genomics. 2005 Mar 21;21(1):105-11

Candidate Genes for Bhr1:

Gene	Genome Location (GRCm39)	Reference	QTL Note
Adam33	Chr2:130892739-130905734 (-)	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 (Bhr1) and 6 (Bhr8) show only asuggestive 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 region of the human genome that has conserved syntenty with the retained A/J regions of chromosome 2 and 6 is large. Human studies have associated SNPs in the ADAM33 gene with asthma. It is notable that metalloprotease Adam33 is located in the retained region on chromosome 2. Recent data in the mouse suggest that differences in Adam33 activity are not likely to account for the strain-specific AHR phenotypes, as a multistrain comparison of 198 potential SNPs in Adam33 genomic sequences (including extensive upstream and downstream regions) found that none differed bewteen the A/J and C57BL/6J strains. (http://mousesnp.roche.com/). Also, dipeptidyl peptidase, DPP10 was found to be associated with asthma in humans and was also reported to be in a region of conserved synteny with mouse loci on chromosome 2 linked to elevated AHR. However, the mouse ortholog of DPP10 (GenBank: AK046842) maps to mouse chromosome 1 and is consequently not a candiate for causing elevated AHR in A/J mice.