Lith4^PERA/EiJ
QTL Variant Detail

Summary

• QTL variant: Lith4^PERA/EiJ
• Name: lithogenic gene 4; PERA/EiJ
• MGI ID: MGI:3576885
• QTL: Lith4 Location: unknown Genetic Position: ChrX, cM position of peak correlated region/allele: 50.14 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: PERA/EiJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers susceptibility to gallstone formation compared to DBA/2J.
• Inheritance: Dominant

Notes

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

J:97424

An initial genome scan was performed with 186 (PERA/EiJ x DBA/2J) F2 animals using 98 SSLP markers at a resolution of 17.1 cM. Parental strain PERA/EiJ is resistant to gallstone formation after 8 weeks on a high fat diet where as parental strain DBA/2J is susceptible. Animals were fed a high fat diet starting at 6-8 weeks of age. After candidate loci were identified an addition set of 93 F2 animals were genotyped at selected regions. This dataset was combined with a previous PERA/EiJ x I/LnJ dataset foradditional analysis.

Significant linkage to gallstone formation mapped near D13Mit88 (LOD=3.1) on mouse Chromosome 13. This locus is named Lith15 (lithogenic gene 15). PERA/EiJ-derived alleles at Lith15 confer susceptibility to gallstone formation with an additive mode of inheritance. When analysis was performed in combination with the I/LnJ dataset the LOD score increased to 3.7 and the Lith15 interval was narrowed to a region on mouse Chromosome 13 between 10 cM - 32 cM with peak linkage at 20 cM.

Significant linkage to gallstone formation mapped near D6Mit44 on mouse Chromosome 6. This locus is named Lith16 (lithogenic gene 16). PERA/EiJ-derived alleles at Lith16 confer susceptibility to gallstone formation with a dominant mode of inheritance. When analysis was performed in combination with the I/LnJ dataset the LOD score increased to 4.5 and the Lith16 interval was narrowed to a region on mouse Chromosome 6 between 42 cM - 64 cM with peak linkage to 56 cM. Lith16 colocalizes with a previously identified QTL named Lith6.

Suggestive linkage to gallstone formation was detected:

on mouse Chromosome 1 (LOD=2.1 near D1Mit64). This QTL has been named Lith26;

on mouse Chromosome 2 (LOD=2.2 near D2Mit113. This QTL has been named Lith27;

on mouse Chromosome 5 (LOD=1.8 near D5Mit95). This QTL has been named Lith29;

on mouse Chromosome 16 (LOD=1.9 near D16Mit4). This QTL has been named Lith28;

and Lith4 on mouse Chromosome X (LOD=2.3 near DXMit149).

The gallstone susceptibily alleles were inherited from thePERA/EiJ parental strain at all loci with the exception of Lith29. At Lith29 the susceptibility allele was inherited dominantly from the DBA/2J strain.

Cross data here was combined with that of a previous study (J:84582) that used a PERA/EiJ x I/LnJ cross. Analysis of the combined data increased the power to detect shared QTL on Chrs 6, 13, 16 and 17 (Lith9) that were associated with the PERA alleles. The combined analysis did not increase the power to detect the suggestive QTLs on Chrs 1, 5 and X.

The Chr 17 QTL, Lith9, did not exceed the threshold for suggestive QTL in the PERA/EiJ x DBA/2J cross but acheived a LOD score of 5.8 at 52cM in the combined data analysis.

Abcg5 (54.5 cM)and Abcg8 (54.5 cM) on mouse Chromosome 17 have been proposed as candidate genes for Lith9. Expression analysis showed higher levels of Abcg5 and Abcg8 mRNA in PERA/EiJ animals compared to DBA/2J and I/LnJ. As expected Abcg5 and Abcg8 mRNA levels didnot differ between DBA/2J and I/LnJ.

References

• Original: J:97424 Wittenburg H, et al., Association of a Lithogenic Abcg5/Abcg8 allele on Chromosome 17 (Lith9) with Cholesterol Gallstone Formation in PERA/EiJ mice. Mamm Genome. 2005;16(7):495-504
• All: 1 reference(s)