Hdlq16^129S1/SvImJ
QTL Variant Detail

Summary

• QTL variant: Hdlq16^129S1/SvImJ
• Name: HDL QTL 16; 129S1/SvImJ
• MGI ID: MGI:3038661
• QTL: Hdlq16 Location: Chr8:93411976-93412125 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: 129S1/SvImJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased HDL cholesterol levels on an atherogenic diet compared to C57BL/6J. (J:88486)
• Inheritance: Not Specified

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Hdlq16 also interacts with Hdlq1 on chromosome 5. Homozygosity for 129S1/SvImJ-derived allele at both Hdlq1 and Hdlq16 significantly decreased plasma HDL concentration in male and female animals fed a CHOW diet.

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

J:88486

Linkage analysis was performed on 294 female (C57BL/6J x 129S1/SvImJ)F2 intercross animals to identify QTLs associated with HDL cholesterol levels and susceptibility to atherosclerosis. 88 polymorphic loci at an average spacing of 20 cM were typed. The animals were placed on a high fat diet for 14 weeks before examination. Parental strain 129S1/SvImJ exhibits elevated HDL cholesterol and resistance to atherosclerotic lesions compared to parental strain C57BL/6J. F1 hybrids exhibit an intermediate phenotype.

Two loci exhibiting significant linkage to HDL cholesterol, Hdlq14 (LOD=5.3 at D1Mit159) and Hdlq15 (LOD=9.7 at D1Mit406), were identified on mouse Chromosome 1 at 80 cM and 104 cM, respectively. A candidate gene mapping near Hdlq15 is Apoa2. An interaction between Hdlq14 and Hdlq15 was identified. Homozygosity for C57BL/6J-derived alleles at Hdlq14 and homozygosity for 129S1/SvImJ-derived alleles at Hdlq15 confers decreased HDL cholesterol levels.

An interaction was also detected between Hdlq15 and Hdlq19 at 90 cM (D2Mit285) on mouse Chromosome 2. Homozygosity for C57BL/6J-derived alleles at Hdlq15 and homozygosity for 129S1/SvImJ-derived alleles at Hdlq19 confers decreased HDL cholesterol levels. Hdlq19 colocalizes with a previously identified QTL named Hdl1 and a previously mapped suggestive locus at D2Mit50 (Colinayo et al, 2003). A candidate gene for Hdlq19 is Pltp.

Hdlq16 mapped to 44 cM on mouse Chromosome 8 (P=0.0283 at D8Mit248). This locus was identified with suggestive linkage in a previous cross and is confirmed in the present study.

Hdlq17 mapped to 24 cM on mouse Chromosome 9 (P=8 x 10-5 at D9Mit129). 129S1/SvImJ-derived alleles confer dominantly-inherited increased HDL cholesterol at Hdlq17. This locus colocalizes with a previously identified suggestive QTL near D9Mit2 (Mehrabian et al, 2000). A candidate gene for Hdlq17 is Apoa1.

Hdlq18 mapped to 22 cM on mouse Chromosome 12 (P=3 x 10-5 at D12Mit172). 129S1/SvImJ-derived alleles confer dominantly-inherited increased HDL cholesterol at Hdlq18.

Ath17 mapped to 34 cM on mouse Chromosome 10 (P=0.0040 at D10Mit31). C57BL/6J-derived alleles confer dominantly-inherited resistance to atherosclerosis at Ath17. This locus partially overlaps a previously identified QTL named Aorls1 (Artles2) but the authors suspect they are separate loci.

An interacting locus pair (Ath18-Ath19) was identified. Ath18 mapped to 16 cM on mouse Chromosome 12 (P=0.0008 at D12Mit243) and Ath19 mapped to 60 cM on mouse Chromosome 11 (P=0.0166at D11Mit333). Homozygosity for C57BL/6J-derived alleles at Ath18 in conjunction with 129S1/SvImJ-derived alleles at Ath19 confers susceptibility to atherosclerosis. Homozygosity for 129S1/SvImJ-derived alleles at Ath18 in conjunction with homozygosity for C57BL/6J-derivedalleles at Ath19 also confers atherosclerosis susceptibility. Ath18 maps near a previously identified QTL named Ath6 but the authors suspect they are separate loci.

Interacting locus pair Ath20-Ath21 was identified. Ath20 mapped to 10 cM on mouse Chromosome 10 (P=0.0065 at D10Mit213) and Ath21 mapped to 50 cM on mouse Chromosome 12 (P=0.0061 at D12Mit7). Homozygosity for 129S1/SvImJ-derived alleles confers increased susceptibility to atherosclerosis regardless of the genotypeat Ath21. However, homozygosity for C57BL/6J-derived alleles at Ath20 in conjunction with 129S1/SvImJ-derived alleles at Ath21 confers atherosclerosis susceptibility. Homozygosity or heterozygosity for 129S1/SvImJ-derived alleles at Ath20 in conjunction with recessive or additive C57BL/6J-derived alleles at Ath21 also confers atherosclerosis susceptibility. Ath20 overlaps with a previously identified QTL named Ath11 (from a different cross), and Ath21 overlaps with a previously identified QTL named Ath7 (from a different cross).

J:144089

Linkage analysis was performed on 528 animals from a (C57BL/6J x 129S1/SvImJ)F2 intercross to map QTL associated with plasma HDL levels on either a CHOW or atherogenic diet. F2 animals were fed a CHOW diet until 8 weeks of age and then placed on an atherogenic diet until 16 weeks of age. An array of 508 SNPs was used for genome scan. Plasma HDL is significantly higher in 129S1/SvImJ parental strain compared to C57BL/7J on CHOW and high fat diets, with a stronger effect observed in males compared to females. Several previously identified HDL QTL were detected in this study as well as several novel loci, some of which showed interactive effects.

On mouse Chromosome 8, a female specific locus named Hdlq44 mapped to 79.7 Mb (34 cM) near rs13479840 (LOD=4.3). This locus displays significant linkage to plasma HDL concentration on CHOW diet with C57BL/6J-derived alleles conferring increased plasma HDL in females. The 95% confidence interval for Hdlq44 spans 71 Mb (33 cM) to 90 Mb (43 cM).

12.15.2014_djr Because Hdlq44 was originally mapped in J:114073 in 2003 using an (C57BL/6J x A/J)F2 intercross, which differs from the cross used here, we consider the current study a separate mapping experiment and have named this QTL Hdlq95.

Hdlq16 (HDL QTL 16) mappeddistally at 107.7 Mb (51 cM) in linkage to plasma HDL concentration on a CHOW diet at rs30731821 (LOD=3.4). C57BL/6J-derived alleles at Hdlq16 confer increased plasma HDL values. The 95% confidence interval for Hdlq16 spans 94 Mb (43 cM) to 121 Mb (61 cM). This locus interacts with Hdlq1 on chromosome 5. Homozygosity for 129S1/SvImJ-derived allele at both Hdlq1 and Hdlq16 significantly decreases plasma HDL concentration in male and female animals on CHOW diet.

References

• Original: J:88486 Ishimori N, et al., Quantitative trait loci analysis for plasma HDL-cholesterol concentrations and atherosclerosis susceptibility between inbred mouse strains C57BL/6J and 129S1/SvImJ. Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):161-6
• All: 2 reference(s)