Phl1^101/H
QTL Variant Detail

Summary

• QTL variant: Phl1^101/H
• Name: progressive hearing loss 1; 101/H
• MGI ID: MGI:3664205
• QTL: Phl1 Location: Chr17:7875843-29487423 bp Genetic Position: Chr17, cM position of peak correlated region/allele: 4.76 cM
• QTL Note: genome coordinates based on the boundaries of the QTL region

Variant origin

• Strain of Specimen: 101/H

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased compound action potential (CAP) thresholds compared to MAI/Pas and MBT/Pas. (J:111682)
• Inheritance: Codominant

Disease models

Notes

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

J:111682

Linkage analysis was performed on 63 (101/H x MAI/Pas)F2 animals and 13 (101/H x MBT/Pas)F2 animals to identify QTL associated with progressive hearing loss. Ninety-four polymorphic markers at an average spacing of 15-20 cM were used for the initial genome scan. Parental strain 101/H exhibits early-onset progressive hearing loss beginning at 2 months of age.

Significant linkage to 24 kHz compound action potential (CAP) threshold mapped to 6.5 cM on mouse Chromosome 17 between D17Mit171 (5 cM) and D17Mit101 (16.4 cM). Peak linkage occurred at D17Mit113 (6.5 cM) with LOD=6.7. This locus explains 34% of the variance and is designated Phl1 (progressive hearing loss 1). Animals homozygous for 101/H-derived alleles at Phl1 exhibit higher CAP thresholds. Phl1is inherited in a co-dominant fashion. Potential candidate genes mapping near Phl1 include Slc22a1 (7.34 cM), Cacna1h (7.5 cM), Sod2 (7.6 cM), and Sox8 (8 cM). The human deafness locus DFNB38 at 6q26-q27 shares synteny with Phl1.

Significant linkage to 34 kHz CAP threshold mapped to 38 cM on mouse Chromosome 10 between D10Mit170 (29 cM) and D10Mit115 (38.4 cM). Peak linkage occurred at D10Mit115 with LOD=5.3. This locus explains 25% of the variance and is named Phl2 (progressive hearing loss 2). F2 animals homozygous for 101/H-derived alleles at Phl2 exhibit higher CAP thresholds. However, heterozygous F2 animals exhibit lower CAP thresholds compared to homozygous wild type F2s indicating a possible heterozygote advantage at Phl2. The age-related hearing loss mutation Cdh23^ahl at 30.3 cM maps near Phl2, but does not segregate with progressive hearing loss indicating these are 2 distinct loci. Candidate genes mapping near Phl2 include Gja1 (29 cM), Ctnna3 (formerly Catna3), and Pcdh15 (40.2 cM).

Phl1 and Phl2 appear tointeract epistatically. Phl2 genotype appears to have little influence in animals homozygous for wild-type alleles at Phl1. The heterozygote advantage of Phl2 (lower CAP thresholds) can be seen in animals heterozygous or homozygous for 101/H-derived allelesat Phl1.

References

• Original: J:111682 Mashimo T, et al., Two quantitative trait loci affecting progressive hearing loss in 101/H mice. Mamm Genome. 2006 Aug;17(8):841-50
• All: 1 reference(s)