Mapping Data

Experiment

• Experiment
  TEXT
• Chromosome
  11
• Reference
  J:139223 Johnson KR, et al., A locus on distal chromosome 11 (ahl8) and its interaction with Cdh23 ahl underlie the early onset, age-related hearing loss of DBA/2J mice. Genomics. 2008 Oct;92(4):219-25
• ID
  MGI:3818002

Genes

Gene	Assay Type
Fscn2	visible phenotype
D11Mit48	PCR amplified length variant
D11Mit104	PCR amplified length variant

Notes

• Experiment
  Linkage analysis was performed on 213 mice from 31 BXD (B=C57BL/6J; D=DBA/2J) recombinant inbred (RI) strains to identify QTL associated with hearing loss. Parental strain DBA/2J displays high frequency (>16 kHz) progressive hearing loss as early as 3 weeks of age whereas C57BL/6J exhibits normal hearing up to 3 months of age. However, both parental strains carry the hearing loss susceptibility allele Cdh23^ahl. Auditory brainstem response (ABR) threshold was measured in BXD RI mice at 6- to 9-months of age as a quantitative trait for hearing loss. Over 750 polymorphic markers were screened for linkage analysis.
  
  Significant linkage to hearing loss (16 kHz ABR threshold) mapped to 77 cM on mouse Chromosome 11 near D11Mit48 (LOD=4.3). This locusis named ahl8 (age related hearing loss 8). The candidate interval for ahl8 spans 113 Mb (71 cM) to 122 Mb (75 cM). A previously identified QTL for acoustic startle response named Sttr1 (118.2 Mb to 120.3 Mb) overlaps with the ahl8 interval.
  
  Analysis of a backcross population of 225 (C57BL/6J x DBA/2J)F1 x DBA/2J mice confirmed the presence of ahl8 with strongest linkage at D11Mit104 (LOD=55.6 for 13 week 16 kHz ABR threshold and LOD=59.9 for 13 week 32 kHz ABR threshold). This locus explained up to70%of the high-frequency hearing loss at 13 weeks of age in the backcross population. Homozygosity for DBA/2J-derived alleles at ahl8 confers increased hearing loss severity at 6- and 13-weeks of age compared to heterozygotes. The DBA/2J susceptibilityallele appearsunique among the inbred strains and acts in conjunction with Cdh23^ahl on chromosome 10.