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

(J:109796)
Animals homozygous for the Chx10<or-J> mutation on a 129X1/SvJ genetic background exhibit blindness, microphthalmia, and closed eyelids. However, outcrossing with inbred strain CASA/Rk results in homozygous Chx10<or-J> offspring with milder phenotypes, indicating genetic modifiers contributed by CASA/Rk.

Linkage analysis was performed on 76 Chx10<or-J> homozygous animals from a (129X1/SvJ-Chx10<or-J> x CASA/Rk)F1 x 129X1/SvJ-Chx10<or-J> backcross to identify modifiers of the Chx10<or-J> mutation. This group is composed of phenotypically extreme animals- 38 mice with the highest eye weight + 38 mice with the lowest eye weights. Fifty-three microsatellite markers with an average spacing of 21.3 cM were used for the genome scan. Linkage was detected on chromosomes 2, 6, and 14. Additional markers were typed to confirm and refine the QTLs.

Significant linkage was detected at 59 cM (125.2 Mb) on mouse Chromosome 6 near D6Mit12 (LOD=3.0). This locus explains 17% of the phenotypic variance and is named Modor1 (modifier of ocular retardation 1). CASA/Rk-derived alleles at Modor1 confer increased eye weight.

Two significant linkages were detected on mouse Chromosome 14. Modor2 (modifier of ocular retardation 2) mapped to 12.5 cM between D14Mit253 and D14Mit154 (LOD=3.3), and Modor3 (modifier of ocular retardation 3) mapped to 42 cM (64.7 Mb) near D14Mit224 (LOD=3.4). CASA/Rk-derived alleles at Modor2 and Modor3 confer increased eye weight. Modor2 and Modor3 each explain 18% and of the trait variance. A potential candidate gene for Modor3 is Rb1 at 38 cM. Linkage analysis with Rb1 showed and association with eye weight (LOD=2.7).

A suggestive locus accounting for 12% of the variance was detected at 28 cM (38.9 Mb) on mouse Chromosome 2 near D2Mit7 (LOD=2.2). 129X1/SvJ-derived alleles confer increased eye weight at this locus.