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QTL Variant Detail
QTL variant: Tmc1m4C3HeB/FeJ
Name: Tmc1 modifier 4; C3HeB/FeJ
MGI ID: MGI:3663121
QTL: Tmc1m4  Location: Chr5:54500177-127001072 bp  Genetic Position: Chr5, cM position of peak correlated region/allele: 29.76 cM
QTL Note: genome coordinates based on the boundaries of the QTL region
Strain of Specimen:  C3HeB/FeJ
Allele Type:    QTL

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


Linkage analysis was performed in 144 (C3HeB/FvJ-Tmc1Bth x C57BL/6J)F1 x C57BL/6J and 180 (C3HeB/FvJ-Tmc1Bth x DBA/2J)F1 x DBA/2J backcross animals to identify modifiers of the Tmc1Bth Beethoven mutation. Parental strain C3HeB/FeJ-Tmc1Bth exhibits deafness by 3 weeks of age, near complete inner hair cell degeneration, and graduated outer hair cell degeneration. Genome scan was performed with polymorphic markers spaced 20 cM apart. Hearing loss was evaluated by distortion product otoacoustic emission (DPOAE) analysis.

A modifier of Tmc1 mapped to 46 cM on mouse Chromosome 2 with LOD=5.8 near D2Mit37. The QTL interval spans 39 cM (D2Mit92) to 75 cM (D2Mit224). This locus explains 16% of the variance and is designated Tmc1m1 (Tmc1 modifier 1). C57BL/6J-derived alleles at Tmc1m1 confer susceptibility to Tcm1Bth-associated hearing loss (decreased DPOEA amplitudes). Potential candidate genes for Tmc1m1 include Tmc2 and Mtap1a (67.5 cM).

Tmc1m2 (Tmc1 modifier 2) mapped to 55 cM on mouse Chromosome 11 with LOD=8.5 near D11Mit70. This locus explains 19% of the variance. The QTL interval spans 33 cM (D11Mit164) to 63 cM (D11Mit253). DBA/2J-derived alleles at Tmc1m2 confer susceptibility to Tcm1Bth-associated hearing loss (decreased DPOEA amplitudes).Myo1c at 44.13 cM is a potential candidate gene for Tmc1m2.

Tmc1m3 (Tmc1 modifier 3) mapped to 3 cM on mouse Chromosome 12 with LOD=4.3 near D12Mit37. The QTL interval spans 1 cM (D12Mit37) to 32 cM (D12Mit52). This locus explains 10% of the variance. DBA/2J-derived alleles at Tmc1m3 confer susceptibility to Tmc1Bth-associated hearing loss (decreased DPOEA amplitudes).

Tmc1m4 (Tmc1 modifier 4) mapped to 61 cM on mouse Chromosome 5 with LOD=3.6 near D5Mit158. The QTL interval spans 40 cM (D5Mit394) to69 cM (D5Mit161). This locus explains 9% of the variance. DBA/2J-derived alleles at Tmc1m4 confer susceptibility to Tmc1Bth-associated hearing loss (decreased DPOEA amplitudes). Previously identified hearing loss QTL Ahl2 at 44 cM overlaps with Tmc1m4.

Suggestive linkage to Tmc1-Bth hearing loss mapped to 60 cM (D15Mit147, LOD=2.8) on mouse Chromosome 15 and 25 cM (D17Mit51, LOD=2.7) on mouse Chromosome 17. C57BL/6J-derived alleles confer decreased hearing loss at both loci.

Original:  J:111838 Noguchi Y, et al., Multiple Quantitative Trait Loci Modify Cochlear Hair Cell Degeneration in the Beethoven (Tmc1Bth) Mouse Model of Progressive Hearing Loss DFNA36. Genetics. 2006 Aug;173(4):2111-9
All:  1 reference(s)

Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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