Hdlq2^SM/J
QTL Variant Detail

Summary

• QTL variant: Hdlq2^SM/J
• Name: HDL QTL 2; SM/J
• MGI ID: MGI:2387160
• QTL: Hdlq2 Location: Chr5:93280786-93280917 bp Genetic Position: Chr5, cM position of peak correlated region/allele: 52.23 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 decreased HDL cholesterol concentration on a high fat diet compared to NZB/BlNJ. (J:76707)
• Inheritance: Other (see notes)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Hdlq2 exhibits additive inheritance.

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

J:76707

90 female animals from an (SM/J x NZB/BlNJ)F1 x NZB/BlNJ backcross population were screened for an initial set of 78 SSLP markers to identify QTLs associated with HDL cholesterol (HDL-C) concentrations. Parental strain NZB/BlNJ exhibits elevated HDL-C onboth a CHOW and atherogenic diet compared to parental SM/J and F1 hybrid animals. A QTL linked to HDL-C on a CHOW diet, Hdlq1, peaked at 65 cM on mouse Chromosome 5 near D5Mit370 (LOD=2.7). NZB-derived alleles confer increased HDL cholesterol concentrations at Hdlq1. Scarb1 was identified as a viable candidate gene, but expression analysis did not reveal a difference in protein or mRNA levels between SM/J and NZB/BlNJ on CHOW or atherogenic diets. Sequence analysis detected a single nucleotide polymorphism between the 2 strains that does not result in an amino acid change. Therefore, Scarb1 is not likely to be the gene underlying Hldq1. A QTL linked to HDL-C on an atherogenic diet, Hdlq2, also mapped to mouse Chromosome 5 and peaks at 45 cM near D5Mit239(LOD=3.6). NZB-derived alleles confer increased HDL-C concentrations at Hdlq2. Both Hdlq1 and Hdlq2 were detected in linkage to HDL-C in previous QTL studies of different crosses such as (NZB/BlNJ x SM/J)F2, (CAST/Ei x C57BL/6J)F2, and (C57BL/6J x C3H/HeJ)F2. Suggestive loci were also detected near D6Mit44 (48 cM) and D18Mit24 (18 cM) in linkage to inducible HDL-C, and on mouse Chromosome 11 at 14 cM and 44 cM in linkage to non-HDL-C on a CHOW diet and non-HDL-C on an atherogenic diet, respectively.

J:89309

Linkage analysis was performed on 513 animals from a (SM/J x NZB/BlNJ)F2 intercross to map QTLs associated with HDL cholesterol levels on a CHOW or atherogenic diet. Genome scan was conducted using 157 polymorphic markers. Parental strain NZB/BlNJ exhibits elevated HDL cholesterol on both CHOW and atherogenic diets compared to parental strain SM/J. Male animals from both strains exhibit increased HDL cholesterol compared to females.

Hdlq20 mapped to 96 cM on mouse Chromosome 1 near D1Mit291 (LOD=11.0 on CHOW diet, LOD=4.1 on Ath diet). The QTL range of Hdlq20 spans 94 cM - 103 cM. NZB/BlNJ-derived alleles confer increased HDL cholesterol with dominant inheritance. Hdlq20 overlaps with previously identified QTL Hdlq5 at 85 cM and may represent the same locus. Apoa2 has been identified as a strong candidate gene for Hdlq20.

Hdlq21 mapped to 56 cM on mouse Chromosome 3 near D3Mit11 (LOD=4.0 on CHOW diet, LOD=3.8 on Ath diet). The QTL range of Hdlq21 spans 34 cM - 60 cM. NZB/BlNJ-derived alleles confer increased HDL cholesterol with additive inheritance.

Previously identified QTLs Hdlq1 (66 cM) and Hdlq2 (50 cM) on mouse Chromosome 5 were detected in this study. Hdlq1 is linked to D5Mit161 (LOD=10.1 on CHOW diet, LOD=12.1 on Ath diet) and Hdlq2 is linkedto D5Mit205 (LOD=7.6 on CHOW diet, LOD=10.8 on Ath diet). Scarb1 and Tcf1 map within the QTL interval of Hdlq1 and are potential candidate genes. A novel QTL named Hdlq22 mapped to 18 cM on mouse Chromosome 5 near D5Mit228 (LOD=5.2 on CHOW diet, LOD=7.6 on Ath diet.) Lrpap1 is proposed as a candidate gene for Hdlq22. NZB/BlNJ-derived alleles confer increased HDL cholesterol with additive inheritance at Hdlq1, Hdlq2, and Hdlq22.

A female-specific QTL named Hdlq23 mapped to 26 cM on mouse Chromosome 6 nearD6Mit74 (LOD=4.2 on CHOW diet). The QTL range of Hdlq23 spans 12 cM - 32 cM. A second QTL named Hdlq24 mapped to 66 cM near D6Mit259 (LOD=6.3 on CHOW diet). The QTL range of Hdlq24 spans 54 cM - 70 cM. Hdlq24 overlaps with previously identified QTLs Hdlq11 (46 cM) and Hdlq12 (71.2 cM). NZB/BlNJ-derived alleles confer increased HDL cholesterol with additive inheritance at both Hdlq23 and Hdlq24.

Hdlq25 maps to 0 cM on mouse Chromosome 8 near D8Mit58 (LOD=4.2 on Ath diet). The QTL range of Hdlq25 spans 0cM - 12 cM. NZB/BlNJ-derived alleles confer increased HDL cholesterol with dominant inheritance.

A female-specific locus named Hdlq26 mapped to 70 cM on mouse Chromosome 10 near D10Mit271 (LOD=4.1 on Ath diet). The QTL range of Hdlq26 spans 60 cM - 70 cM.NZB/BlNJ-derived alleles confer increased HDL cholesterol with recessive inheritance. A potential candidate gene for Hdlq26 is Apof.

A female-specific locus named Hdlq27 mapped to 48 cM on mouse Chromosome 15 near D15Mit70 (LOD=4.2 on CHOW diet). The QTL range of Hdlq27 spans 44 cM - 60 cM. NZB/BlNJ-derived alleles confer increased HDL cholesterol with recessive inheritance. Hdlq27 overlaps with a previously identified QTL named Pltpq4 (phospholipid transfer protein activity QTL 4). Candidate gene Pparamaps to this region and exhibits 4-fold greater expression in male SM/J on a CHOW diet compared to NZB/BlNJ.

Hdlq28 mapped to 26 cM on mouse Chromosome 16 near D16Mit57 (LOD=3.7 on CHOW diet). The QTL range of Hdlq28 spans 0 cM - 60 cM. NZB/BlNJ-derived alleles confer increased HDL cholesterol with dominant inheritance. Apod has been suggested as a candidate gene for Hdlq28.

A male-specific locus named Hdlq29 mapped to 36 cM on mouse Chromosome 17 near D17Mit20 (LOD=4.5 on Ath diet). NZB/BlNJ-derived alleles confer increased HDL cholesterol with additive inheritance. Potential candidate genes for Hdlq29 are Abcg5 and Abcg8.

Hdlq30 mapped to 48 cM (LOD=4.2 on CHOW diet at D18Mit9) and Hdlq31 mapped to 56 cM (LOD=5.2 cM on Ath diet at D18Mit4) on mouseChromosome 18. The QTL range of Hdlq31 spans 42 cM - 60 cM. A potential candidate gene for Hdlq31 is Lipg. NZB/BlNJ-derived alleles confer increased HDL cholesterol with additive inheritance at both Hdlq30 and Hdlq31.

A female-specific locus named Hdlq32 mapped to 26 cM on mouse Chromosome 19 near D19Mit11 (LOD=4.0 on Ath diet). The QTL range of Hdlq32 spans 10 cM - 70 cM. NZB/BlNJ-derived alleles confer increased HDL cholesterol with recessive inheritance. Hdlq32 overlaps with a previously identified QTL named Chab5 (cholesterol absorption 5) at 16 cM. Fas has been proposed as a candidate gene for both Hdlq32 and Chab5. Vldlr is also a potential candidate gene for Hdlq32.

References

• Original: J:76707 Pitman WA, et al., Quantitative trait locus mapping of genes that regulate HDL cholesterol in SM/J and NZB/B1NJ inbred mice. Physiol Genomics. 2002;9(2):93-102
• All: 2 reference(s)