Gct8^SWXJ9/BmJ
QTL Variant Detail

Summary

• QTL variant: Gct8^SWXJ9/BmJ
• Name: granulosa cell tumorigenesis 8; SWXJ9/BmJ
• MGI ID: MGI:3574508
• QTL: Gct8 Location: Chr2:166236907-166237050 bp Genetic Position: Chr2, cM position of peak correlated region/allele: 86.75 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: SWXJ9/BmJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers susceptibility to granulosa cell turmor formation compared to CAST/Ei. (J:96787)
• Inheritance: Not Specified

Tumor Data

List all tumor models in MMHCdb carrying Gct8^SWXJ9/BmJ

Notes

This locus also shows interaction with a locus on mouse Chromosome 10 at D10Mit80 (4 cM). Homozygosity for SWXJ9/BmJ-derived alleles at Gct8 in conjunction with heterozygosity for SWXJ9/BmJ and CAST/Ei at D10Mit80 confers additional susceptibility to ovarian granulosa cell tumors.

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

J:96787

Linkage analysis was performed on 1968 female animals from a (CAST/Ei x SWXJ9/BmJ)F1 x SWXJ9/BmJ backcross to identify QTLs associated with susceptibility to juvenile-onset ovarian granulosa cell tumor development. Parental strain SWXJ9/BmJ is a susceptible recombinant inbred strain derived from SWR and SJL. Parental strain CAST/EI is resistant to developing granulosa cell tumors. 81 polymorphic markers at an average spacing of 20 cM were used in the genome scan. A previously mapped QTL, 3 novel QTLs, and 2 interacting locus pairs reaching genome-wide statistical significance were mapped in this study. These loci collectively account for 48.2% of the phenotypic variance.

Previously identified Gct1 on mouse Chromosome 4 was detected in this study. Gct1 showed significant linkage at 74 cM with LOD=5.2 at D4Mit232. The 95% confidence interval of Gct1 spans 70 cM to 80 cM. Homozygosity for SWXJ9/BmJ-derived alleles at Gct1 confers susceptibility to ovarian granulosa cell tumors. The Gct locus is syntenic toa region on human Chromosome 1p36 that is frequently found deleted in human cancers.

1.12.2015 Curator Note: Because Gct1 was originally mapped in J:49710 in 1998 using reciprocal crosses between SJL X SWR mice, which differs from the cross used here,we consider the current study a separate mapping experiment and have named this QTL Gct5.

Gct7 maps to 48 cM on mouse Chromosome 1 with LOD=6.6 at D1Mit125. The 95% confidence interval of Gct7 spans 34 cM to 56 cM. Homozygosity for SWXJ9/BmJ-derived alleles at Gct7confers susceptibility to ovarian granulosa cell tumors.

Gct8 maps to 96 cM on mouse Chromosome 2 with LOD=2.8 at D2Mit145. The 95% confidence interval of Gct8 spans 70 cM to 98 cM. Homozygosity for SWXJ9/BmJ-derived alleles at Gct8 confers susceptibility to ovarian granulosa cell tumors. This locus also shows interaction with a locus on mouse Chromosome 10 at D10Mit80 (4 cM). Homozygosity for SWXJ9/BmJ-derived alleles at Gct8 in conjunction with heterozygosity at D10Mit80 confers additionalsusceptibility to ovarian granulosa cell tumors.

Gct9 maps to 60 cM on mouse Chromosome 13 with LOD=3.6 at D13Mit292. The 95% confidence interval of Gct9 spans 46 cM to 62 cM. Homozygosity for SWXJ9/BmJ-derived alleles at Gct9 confers susceptibility to ovarian granulosa cell tumors.

An interacting locus pair was detected at D17Mit187 (47.4 cM) and D18Mit12 (17 cM). These loci do not reach statistical significance individually. Susceptibility to granulosa cell tumors is increased when both D17Mit187 andD18Mit12 are homozygous for SWXJ9/BmJ-derived alleles or heterozygous for SWXJ/BmJ and CAST/Ei.

References

• Original: J:96787 Dorward AM, et al., Distal Chr 4 harbors a genetic locus (Gct1) fundamental for spontaneous ovarian granulosa cell tumorigenesis in a mouse model. Cancer Res. 2005 Feb 15;65(4):1259-64
• All: 1 reference(s)