Gpdc1^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Gpdc1^C57BL/6J
• Name: G protein deficiency-induced colitis 1; C57BL/6J
• MGI ID: MGI:3573767
• QTL: Gpdc1 Location: unknown Genetic Position: Chr3, cM position of peak correlated region/allele: 56.07 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Inheritance: Dominant

Notes

Gpdc1 participates in epistatic interactions with Gpdc2.

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

J:95140

Genome scan was performed on 284 homozygous mutant animals from a (C57BL/6J-Gnai2^tm1Uru x C3H/HeN-Gnai2^tm1Uru)F2 intercross to identify loci modifying colitis susceptibility and severity. Parental strain C3H/HeN-Gnai2^tm1Uru is extremely susceptibleto colitis whereas parental strain C57BL/6J-Gnai2^tm1Uru is resistant. C3H/HeN-Gnai2^tm1Uru displays severe diarrhea, weight loss, rectal prolapse, and dilation of the colon as early as 6 weeks of age. C3H/HeN-Gnai2^tm1Uru mice have a low survival rate and breed poorly so they were maintained as heterozygotes. 134 microsatellite markers at an average spacing of 12.4 cM were used for the genome scan. Female F2 animals showed an increased susceptibility to colitis.

A significant colitis susceptibility locus mapped to 61 cM on mouse Chromosome 3 near D3Mit348 (LOD=7). This locus is named Gpdc1 (G protein deficiency-induced colitis 1). C3H/HeN-derived alleles confer colitis susceptibility with a recessive mode of inheritance. Gpdc1 shows epistatic interaction with Gpdc2 on chromosome 1. Gpdc1 coincides with a previously identified colitis susceptibility QTL at 62 cM named Cdcs1. Potential candidate genes in this region are Egf (65.2 cM), Gbp1 (67.4 cM), and Nfkb1 (68.9 cM).

A second locus named Gpdc2 (Gprotein deficiency-induced colitis 2) mapped to 47 cM on mouse Chromosome 1 near D1Mit308 (LOD=4.3). This QTL spans a broad interval of 30 cM. C3H/HeN-derived alleles confer colitis susceptibility with a recessive mode of inheritance. Gpdc2 shows epistatic interaction with Gpdc1 on chromosome 3.

Gpdc3 mapped to 42 cM on mouse Chromosome 9 near D9Mit123. This locus reached suggestive significance in the initial analysis but when Gpdc1 was held constant the statistical significance of Gpdc3 reached borderline genome-wide significance. C3H/HeN-derived alleles at Gpcd3 confer susceptibility to colitis. Gpdc3 shows epistatic interaction with a C3H/HeN-derived locus on chromosome 7. Gpdc3 coincides with previously identified colitis QTLs Tnbs1 (48 cM) and Ibdq1.

A suggestive locus mapped to 73.3 cM on mouse Chromosome X. C3H/HeN-derived alleles confer susceptibility to colitis at this locus.

References

• Original: J:95140 Borm ME, et al., A major quantitative trait locus on mouse chromosome 3 is involved in disease susceptibility in different colitis models. Gastroenterology. 2005 Jan;128(1):74-85
• All: 1 reference(s)