Mrdq2^C57BL/6
QTL Variant Detail

Summary

• QTL variant: Mrdq2^C57BL/6
• Name: modifier of retinal degeneration QTL 2; C57BL/6
• MGI ID: MGI:3803143
• QTL: Mrdq2 Location: Chr5:110253106-118093673 bp Genetic Position: Chr5, Syntenic

Variant origin

• Strain of Specimen: C57BL/6

Variant description

• Allele Type: QTL
• Inheritance: Dominant

Notes

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

J:136923

Linkage analysis was performed on 431 (BALB/cByJ-Rd3^rd3 x B6.Cg-Tyr^c-2J Rd3^rd3)F2 animals to identify genetic modifiers of retinal degeneration. One hundred forty-eight SNP markers spaced 10.7 cM apart were used for genome scan. Retinal outer nuclear layer (ONL) was measured in F2 animals between 5-12 weeks of age. Parental strain BALB/cByJ-Rd3^rd3 displays rapid degeneration of the retinal ONL between 9- to 12-weeks of age compared to parental strain B6.Cg-Tyr^c-2J Rd3^rd3. Five significant QTLs were identified. Additional SNP markers were analyzed to refine the QTL interval for the three strongest linkages on chromosomes 17, 5 and 8.

Significant linkage to retinal degeneration mapped to mouse Chromosome 17 between rs3145545 (30.5 Mb) and rs13483008 (47.2 Mb) with LOD=19.6. This locus explains 19% of the phenotypic variance and is named Mrdq1 (modifier of retinal degeneration QTL 1). The QTL critical region spans a 16.7 Mb interval. C57BL/6-derived alleles at Mrdq1 confer decreased retinal degeneration with an additive mode of inheritance. Potential candidate genes displaying increased expression in the mouse eye of retinal degeneration strains include Guca1a, Guca1b, Rrp1b, Pla2g7 and Zfp472.

Mrdq2 (modifier of retinal degeneration QTL 2) mapped to mouse Chromosome 5 between rs13459186 (110.4 Mb) and rs13478483 (118.2 Mb) with LOD=24.7. This locus explains 16% of the phenotypic variance. BALB/cByJ-derived alleles at Mrdq2 confer decreased retinal degeneration with a recessive mode of inheritance. The Mrdq2 critical region encompasses a 7.8 Mb interval. Ccdc64 is a potential candidate gene for Mrdq2 displaying increased gene expression in the mouse eye of retinal degeneration strains.

Mrdq3 (modifier of retinal degeneration QTL 3) mapped to mouse Chromosome 8 between rs13479995 (116.6 Mb) andrs6310608 (128.2 Mb) with LOD=16.2. C57BL/6-derived alleles at Mrdq3 confer decreased retinal degeneration with an additive mode of inheritance. The QTL critical region spans 11.6 Mb. Mrdq3 explains 10% of the phenotypic variance. Wwox displays increased gene expression in the mouse eye of retinal degeneration strains and is a potential candidate gene for Mrdq3.

On mouse Chromosome 14, a locus between rs6290836 (11.3 Mb) and rs13482170 (47.5 Mb) displayed significant association with retinal degeneration.This locus explains 4% of the phenotypic variance and is named Mrdq4 (modifier of retinal degeneration QTL 4). The QTL critical region spans a 36.2 Mb interval. C57BL/6-derived alleles at Mrdq4 conferdecreased retinal degeneration with additive inheritance.

Mrdq5 (modifier of retinal degeneration QTL5) is located on mouse Chromosome 6 between rs13478697 (32.8 Mb) and rs13478841 (78.2 Mb) with LOD=5.3. C57BL/6-derived alleles at Mrdq5 confer a protective effect against retinal degeneration with additive inheritance. This locus explains 3% of the phenotypic variance and the QTL critical region spans a 35.4 Mb interval. Mrdq5 overlaps with a previously identified QTL for age-related retinal degeneration named Arrd1 at 35 cM.

Loci reaching suggestive statistical significance of LOD=2.7 were identifiedon mouse Chromosome 7 between rs8255275 (46 Mb) and rs3663988 (139.2 Mb) and mouse Chromosome 1 between the centromere and rs3685919 (111.5 Mb). The suggestive loci each explain 1% of the phenotypic variance with C57BL/6-derived alleles conferring recessive protection against retinal degeneration.

References

• Original: J:136923 Danciger M, et al., Genetic modifiers of retinal degeneration in the rd3 mouse. Invest Ophthalmol Vis Sci. 2008 Jul;49(7):2863-9
• All: 1 reference(s)