Lith18^SM/J
QTL Variant Detail

Summary

• QTL variant: Lith18^SM/J
• Name: lithogenic gene 18; SM/J
• MGI ID: MGI:3577245
• QTL: Lith18 Location: Chr8:93402145-93402251 bp Genetic Position: Chr8, cM position of peak correlated region/allele: 44.99 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: SM/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased gallstone weight and incidence compared to NZB/BlNJ. (J:97646)
• Inheritance: Other (see notes)

Notes

Lith18 exhibits additive inheritance.

Lith 18 and Lith22 show interactive effects. NZB-derived alleles at Lith22 and SM/J-derived alleles at Lith18 confer increased gallstone weight and incidence.

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

J:97646

Linkage analysis was performed on 489 (SM/J x NZB/BlNJ)F2 animals to identify QTLs associated with susceptibility to gallstone formation. Parental strain NZB/BlNJ is susceptible to gallstone development on a high fat diet whereas parental strain SM/J is resistant. Animals were placed on a high fat, high cholesterol diet for 18 weeks starting at 6-8 weeks of age. 154 SSLP markers were used for the genome scan.

Significant linkage to gallstone weight and gallstone presence mapped to mouse Chromosome 5 at 60 cM (Lith17) and 76 cM (Lith18). Lith17 is linked to D5Mit24 with LOD=3.4 for gallstone weight and LOD=5.4 for gallstone presence. The Lith17 95% confidence interval spans 40 cM - 65 cM. SM/J-derived alleles at Lith17 confer increased gallstone weight and incidence with an additive mode of inheritance. Lith17 locus shows overlap with a previously identified gallstone QTL named Lith13 (30 cM). Lith18 is linked to D8Mit284 with LOD=4.3 for gallstone weight and LOD=3.9 for gallstone presence. The 95% confidence interval of Lith18 spans 70 cM - 80 cM. SM/J-derived alleles at Lith18 confer increased gallstone weight and incidence with an additive mode of inheritance.

Lith19 mapped to 0 cM on mouse Chromosome 8 near D8Mit155 with LOD=5.1 for gallstone weight and LOD=5.3 for gallstone presence. The 95% confidence interval of Lith19 spans 0 cM - 8 cM. SM/J-derived alleles at Lith19 confer increased gallstone weight and incidence with a recessive mode of inheritance. A potential candidate gene for Lith19 is Slc10a2 at 2 cM.

Suggestive linkage to gallstone weight mapped to 44 cM on mouse Chromosome 9 near D9Mit73 (LOD=2.7). This locus is named Lith20 because it confirms a linkage detected in a previous cross. The 95% confidence interval of Lith20 spans 33 cM -50 cM. SM/J-derived alleles at Lith20 confer increased gallstone weight with a recessive mode of inheritance. Lith5 colocalizes with Lith20 and is thought to be the same QTL.

Suggestive linkage to gallstone presence mapped to 24 cM on mouse Chromosome 10 with LOD=2.9 at D10Mit214. This locus named Lith21 because it confirms a linkage detected in a previous cross. The 95% confidence interval of Lith21 spans 10 cM - 40 cM. NZB/BlNJ-derived alleles confer increased gallstone incidence with a recessive mode of inheritance.

An interacting locus named Lith22 was detected at 65 cM on mouse Chromosome 7 near D7Mit12. NZB-derived alleles at Lith22 and SM/J-derived alleles at Lith18 confer increased gallstone weight and incidence.

An interacting locus named Lith23 was detected at 13 cM on mouse Chromosome 11 near D11Mit152. SM/J-derived alleles at Lith23 and Lith19 confer increased gallstone weight.

Suggestive linkage to gallstone presence mapped to 26 cM on mouse Chromosome 17 near D17Mit177 (LOD=2.2). NZB/BlNJ-derived alleles at this locus confer increased gallstone incidence. Previously identified gallstone QTL Lith3 (3.5 cM) maps near the suggestive locus.

References

• Original: J:97646 Lyons MA, et al., Single and interacting QTLs for cholesterol gallstones revealed in an intercross between mouse strains NZB and SM. Mamm Genome. 2005 Mar;16(3):152-63
• All: 1 reference(s)