Plast2b^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Plast2b^C57BL/6J
• Name: plasma plant sterol 2b; C57BL/6J
• MGI ID: MGI:3703772
• QTL: Plast2b Location: Chr2:84013198-148522175 bp Genetic Position: Chr2, cM position of peak correlated region/allele: 49.35 cM
• QTL Note: genome coordinates based on the boundaries of the QTL region

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased plasma plant sterol concentrations compared to CASA/Rk. (J:119976)
• Inheritance: Recessive

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

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

J:119976

Linkage analysis was performed on 201 (C57BL/6J x CASA/Rk)F2 intercross animals to map genetic loci associated with plasma plant sterol concentrations. Two hundred fifty-five polymorphic markers at a resolution of 5.9 cM were used for the genome scan. Parental strain C57BL/6J displays 50% lower plasma campesterol and 25% lower plasma sitosterol compared to parental strain CASA/Rk. Animals were phenotyped at 11 weeks of age. It was shown that total daily food intake did not differ between parental strains.

Significant linkage to plasma plant sterol levels mapped to 16.5 cM on mouse Chromosome 14 near D14Mit18 (LOD=9.9). This locus is named Plast1 (plasma plant sterol 1). C57BL/6J-derived alleles at Plast1 confer increased plasma plant sterol concentrations with codominant inheritance. This locus explains 23% of the variance. Plast1 exhibits interaction with 3 other loci on chromosomes 2, 5, and 7.

Two linkages to plasma plant sterol levels mapped to mouse Chromosome 2. The proximal locus, Plast2a, peaks at 18 cM near D2Mit296 (LOD=4.1). The distal locus, Plast2b, peaks at 65 cM between D2Mit126 (48 cM) and D2Mit405 (69 cM) (LOD=3.7). C57BL/6J-derived alleles at Plast2a confer increased plasma plant sterol concentrations with codominant inheritance while C57BL/6J-derived alleles at Plast2b confer increased plasma plant sterol concentrations with recessive inheritance. Plast2a and Plast2b explain 9% and 8% of the variance, respectively. These two loci also exhibit suggestive linkage to plasma total cholesterol levels (LOD=3.1). Potential candidate genes for Plast2a include Abca2 (12.6 cM) and Rxra (17 cM). Potential candidate genes for Plast2b include Nr1h3 (formerly Lxra, 40.4 cM) and Ncoa6 (formerly PRIP). A previously identified cholesterol absorptionQTL named Chab1(60 cM) maps in the vicinity of Plast2b.

Interaction between Plast1, Plast2b and loci at 66 cM on chromosome 5 (Plast3) and 0 cM on chromosome 7 (Plast4) were detected. The interaction between Plast1 and Plast2b, Plast3, and Plast4 reachedLOD=16.44, LOD=13.63, and LOD=13.37, respectively. Homozygosity for CASA/Rk-derived alleles at Plast2b in conjunction with at least 1 C57BL/6J-derived allele at Plast1 significantly decreases plasma campsterol-to-total cholesterol ratio. Interaction between Plast2b and Plast3 reached LOD=9.76.

References

• Original: J:119976 Sehayek E, et al., Loci on chromosomes 14 and 2, distinct from ABCG5/ABCG8, regulate plasma plant sterol levels in a C57BL/6J x CASA/Rk intercross. Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16215-9
• All: 1 reference(s)