Nhdlq4^129S1/SvImJ
QTL Variant Detail

Summary

• QTL variant: Nhdlq4^129S1/SvImJ
• Name: non-HDL QTL 4; 129S1/SvImJ
• MGI ID: MGI:3497792
• QTL: Nhdlq4 Location: Chr10:122041304-122041528 bp Genetic Position: Chr10, cM position of peak correlated region/allele: 70.36 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: 129S1/SvImJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased non-HDL cholesterol compared to C57BL/6J.
• Inheritance: Recessive

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Nhdlq4 shows interactive effects with Nhdlq5 and Nhdlq7.

Homozygosity for 129S1/SvImJ-derived alleles at Nhdlq4 in conjunction with homozygosity for C57BL/6J-derived alleles at Nhdlq5 confers significantly increased non-HDL concentrations.

Homozygosity for 129S1/SvImJ-derived alleles at Nhdlq4 in conjunction with homozygosity for C57BL/6J-derived alleles at Nhdlq7 confers significantly increased non-HDL concentrations.

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

J:93243

Genome scan was performed on 294 (C57BL/6J x 129S1/SvImJ)F2 female animals to identify loci associated with plasma lipids and obesity. 88 SSLP markers at an average spacing of 20 cM across the genome were genotyped for linkage analysis. Animals were placed on a high fat diet for 14 weeks. Parental strain C57BL/6J exhibits increased non-HDL levels, decreased plasma triglycerides, lower % body fat, and lower body mass index (BMI) compared to parental strain 129S1/SvImJ.

A previously identified QTL named Nhdlq1 (non-HDL QTL 1) was detected and confirmed in this study.

03.31.2015 Curators Note: Because Nhdlq1 was originally mapped in 2004 in J:88732 using a (CAST/Ei x 129/SvImJ)F2 intercross, which differs from the cross used here, we consider the currentstudy a separate mapping experiment and have named the QTL Nhdlq14.

Nhdlq14 maps to 38 cM on mouse Chromosome 8 with LOD=4.4 at D8Mit248. The 95% confidence interval for Nhdlq14 spans 15 cM - 52 cM. C57BL/6J-derived alleles confer increased non-HDL concentrations with a dominant mode of inheritance at Nhdlq14. Potential candidate genes for Nhdlq14 are Lpl (33 cM) and Cpe (32.6 cM). This locus was observed to interact with a locus at 8 cM (D7Mit294) on mouse Chromosome 7 named Nhdlq6. Homozygosity for C57BL/6J-derived alleles at Nhdlq14 in conjunction with homozygosity for 129S1/SvImJ-derived alleles at Nhdlq6 confers significantly increased non-HDL concentrations. The 95% confidence interval for Nhdlq6 spans 5 cM - 20 cM. A potential candidate gene forNhdlq6 is Apoc2 (4 cM).

Nhdlq4 mapped to 70 cM on mouse Chromosome 10 with LOD=4.0 at D10Mit35a. The 95% confidence interval of Nhdlq4 spans 65 cM - 70 cM. 129S1/SvImJ-derived alleles confer increased non-HDL concentrations with a recessive mode of inheritance at Nhdlq4. Nhdlq4 overlaps with a previously identified phospholipid transfer QTL named Pltpq2 (66 cM). A potential candidate gene for Nhdlq4 is Apof (73 cM). This locus was observed to interact with a locus at 0 cM on mouse Chromosome 6 named Nhdlq5. The 95%confidence interval for Nhdlq5 span 0 cM - 24 cM and peak linkage is at D6Mit86 (LOD=2.4). Homozygosity for 129S1/SvImJ-derived alleles at Nhdlq4 in conjunction with homozygosity for C57BL/6J-derived alleles at Nhdlq5 confers significantly increased non-HDL concentrations.

Nhdlq4 also interacts with a locus on mouse Chromosome 15 at D15Mit13 (0 cM). The interacting locus was named Nhdlq7. The 95% confidence interval for Nhdlq7 span 0 cM - 20 cM. Homozygosity for 129S1/SvImJ-derived alleles atNhdlq4 in conjunction with homozygosity for C57BL/6J-derived alleles at Nhdlq7 confers significantly increased non-HDL concentrations.

Triglyceride QTL Tgq1 mapped to 42 cM on mouse Chromosome 18 with LOD=3.2 at D18Mit50. The 95% confidence interval forTgq1spans37 cM - 44 cM. Heterozygosity for C57BL/6J and 129S1/SvImJ alleles at Tgq1 confers increased plasma triglycerides.

Two interacting triglycerides QTLs named Tgq2 and Tgq3 were identified at 66 cM on mouse Chromosome 9 (LOD=2.2 at D9Mit281) and58 cMon mouse Chromosome 4 (D4Mit308), respectively. The 95% confidence interval of Tgq2 spans 44 cM - 68 cM and the 95% confidence interval of Tgq3 spans 30 cM - 90 cM. Homozygosity for C57BL/6J-derived alleles at Tgq2 in conjunction with homozygosity for 129S1/SvImJ-derived alleles at Tgq3 contribute to significantly increased triglycerides. Potential candidate genes for Tgq3 are Lepr (46.7 cM), Cpt2 (54.4 cM), and Angptl3 (48.5 cM).

A new obesity QTL named Obq16 was identified at 48 cM on mouse Chromosome8.The 95% confidence interval of Obq16 spans 42 cM - 53 cM and peak linkage occurs at D8Mit248 (LOD=10). 129S1/SvImJ-derived alleles confer additively inherited increase in % body fat at Obq16. Obq16 also shows linkage to body mass index (LOD=2.5)with 129S1/SvImJ-derived alleles conferring increased BMI. Obq16 interacts with a locus at 65 cM (D9Mit281) on mouse Chromosome 9 named Obq18. Obq18 does not have an effect by itself but the C57BL/6J allele has an additive or codominant effect in conjunction with homozygosity at Obq16 for 129S1/SvImJ alleles. Animals with this genotype exhibit significantly increased % body fat. The 95% confidence interval of Obq18 spans 0 cM - 75 cM. Obq18 overlaps with a previously identified adiposity QTL named Adip5 but these are thought be separate and distinct QTLs.

A previously identified obesity QTL named Mob2 was detected and confirmed as a suggestive locus in this study. Mob2 maps to 0 cM on mouse Chromosome 6 with LOD=2.6 at D6Mit86.

02.12.2015 Curators Note:Because Mobq2 (Mob2) was originally mapped in J:14189 in 1993 using a (C57BL/6J x M.spretus)F1 x C57BL/6J backcross, which differs from the cross used here, we consider the current study a separate mapping experiment and have named the QTL Mobq9.

A suggestive obesity locus at 74 cM on mouse Chromosome 1 named Obq17 was identified. The 95% confidence interval of Obq17 spans 48 cM - 108 cM. Obq17 reaches peak linkage at D1Mit495 (LOD=2.3). 129S1/SvImJ-derived alleles confer increased % body fat at Obq17. Obq17 alsoshows linkage to body mass index (LOD=2.4) with 129S1/SvImJ-derived alleles conferring increased BMI. Obq17 overlaps with previously identified obesity QTLs Obq8 and Obq9, which were mapped using different inbred strains.

A locus associated with bodymass index, Obq19, was identified at 8 cM on mouse Chromosome 17 (LOD=2.9 at D17Mit143). The 95% confidence interval of Obq19 spans 1 cM - 25 cM. C57BL/6J-derived alleles confer increased BMI at Obq19. Potential candidate genes for Obq19 are Ppard (13.5 cM),Igf2r (7.35 cM), and Acat2 (7.55 cM).

References

• Original: J:93243 Ishimori N, et al., Quantitative trait loci that determine plasma lipids and obesity in C57BL/6J and 129S1/SvImJ inbred mice. J Lipid Res. 2004 Oct;45(9):1624-32
• All: 1 reference(s)