Hdlq13^CAST/Ei
QTL Variant Detail

Summary

• QTL variant: Hdlq13^CAST/Ei
• Name: HDL QTL 13; CAST/Ei
• MGI ID: MGI:3037949
• QTL: Hdlq13 Location: unknown Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: CAST/Ei

Variant description

• Allele Type: QTL
• Inheritance: Other (see notes)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Hdlq5 exhibits additive inheritance.

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

J:88732

Genome scan was performed on 277 male animals from a (CAST/Ei x 129/SvImJ)F2 intercross to identify QTLs associated with lipoprotein cholesterol levels. The animals were placed on an atherogenic diet for 8 week. Parental strain CAST/Ei exhibits decreasedHDL cholesterol, but increased total and non-HDL cholesterol compared to parental strain 129/SvImJ.

Two previously identified QTLs affecting HDL cholesterol levels, Hdlq5 and Hdlq10, were detected in this study. Hdlq5 mapped to 85 cM on mouse Chromosome1 near D1Mit102 (LOD=5.1). The 95% confidence interval of Hdlq5 spans from 60 cM - 100 cM and this locus explains 8% of the phenotypic variance. 129/SvImJ-derived alleles confer increased HDL cholesterol with additive inheritance at Hdlq5. Other QTLs colocalizing with Hdlq5 are Hdlq6, Tnfsf4, Pcho1, and Chab6. Candidate genes mapping to this region are Apoa2 and Nr5a2. Apoa2 is differentially expressed between 129/SvImJ and CAST/Ei and is considered a strong candidate gene.

12.09.2014 Curator Note: Because Hdlq5 was originally mapped in J:84430 in 2003 using a (C57BL/6J x NZB/BlNJ)F1 x C57BL/6J backcross, which differs from the cross used here, we consider the current study a separate mapping experiment and have named this QTL Hdlq13.

Hdlq10 mapped to 20 cM on mouseChromosome 4 near D4Mit110 (LOD=3.7). The 95% confidence interval of Hdlq10 spans from 10 cM - 30 cM and this locus explains 6% of the phenotypic variance. CAST/Ei-derived alleles confer increased HDL cholesterol with additive inheritance atHdlq10. Other QTLs colocalizing with Hdlq10 are Lch and Lch2. Abca1 is a candidate gene for Hdlq10.

12.09.2014 Curator Note: Because Hdlq10 was originally mapped in J:83460 in 2003 using a (CAST/Ei x DBA/2J)F2 cross, which differs from the cross used here, we consider the current study a separate mapping experiment and have namedthis QTL Hdlq67.

Three novel QTLs affecting total cholesterol levels, Chol7, Chol8, and Chol9 were identified. Chol7 mapped to 74 cM on mouse Chromosome 1 near D1Mit102 (LOD=3.3). The 95% confidence intervalofChol7 spans 65 cM - 80 cM and this locus explains 5.3% of the phenotypic variance. 129/SvImJ-derived alleles confer increased total cholesterol with additive inheritance at Chol7. Other QTLs colocalizing with Chol7 areHdlq6, Ath1, Pcho1, and Chab6. Candidate genes mapping to this region are Apoa2and Nr5a2. Authors state that Chol7 and Hdlq5 are most likely 2 distinct loci although they map to the same region.

Chol8 mapped to 12 cM on mouse Chromosome 4 near D4Mit194 (LOD=4.7). The 95% confidence interval of Chol8 spans 0 cM - 30 cM and this locusexplains 7.6% of the phenotypic variance. CAST/Ei-derived alleles confer increased total cholesterol with dominant inheritance at Chol8. Other QTLs colocalizing with Chol8 areLch andLch2. Abca1 and Cyp7a1are candidate genes for Chol8. Authors state thatthe same gene may underly Hdlq10 and Chol8 since both QTLs map to the same region.

Chol9 mapped to 54 cM on mouse Chromosome 17 near D17Mit221 (LOD=3.2). The 95% confidenceintervalof Chol8 spans 20 cM - 60cM and this locus explains 5.2% of the phenotypicvariance. CAST/Ei-derived alleles confer increased total cholesterol with dominant inheritance at Chol9. Hdl4 is a previously identified QTL colocalizing with Chol9. Candidate genesmapping near Chol9 areAbcg5 and Abcg8.

Loci showing suggestive linkage tototal cholesterol mapped to 20 cM on mouse Chromosome 7 (LOD=2.4 at D7Mit246), 50 cM on mouse Chromsome 8 (LOD=2.9 at D8Mit248), and to 68 cM on mouse Chromosome 15 (LOD=2.3 atD15Mit79).

Two non-HDLQTLs were identified in this study. Nhdlq1 mapped to 34cMon mouse Chromosome 8 near D8Mit248 (LOD=3.8). The 95% confidence interval of Nhdlq1 spans 20 cM - 60 cM and this locus explains 6.1% of the phenotypic variance. CAST/Ei-derived alleles confer increased non-HDL cholesterol with additive inheritance atNhdlq1. Candidate genes mapping Nhdlq1 are Cpe and Lpl.

Nhdlq2 mapped to 6 cM on mouse Chromosome X near DXMit81 (LOD=4.6). The 95% confidence interval of Nhdlq2 spans0 cM-18 cMand this locus explains 4.6% of the phenotypic variance. 129/SvImJ -derivedalleles confer increased non-HDL cholesterol at Nhdlq2.

A suggestive locus associated with non-HDL cholesterol mapped to 20 cM on mouse Chromosome 15 (LOD=2.8 at D15Mit115).

References

• Original: J:88732 Lyons MA, et al., Quantitative trait loci that determine lipoprotein cholesterol levels in an intercross of 129S1/SvImJ and CAST/Ei inbred mice. Physiol Genomics. 2004 Mar 12;17(1):60-8
• All: 1 reference(s)