Experiment
Linkage analysis was performed on 241 female animals from a (C57BL/6J-Apoetm1Unc x C3H/HeJ-Apoetm1Unc/Wshi)F2 intercross to identify QTLs for carotid artery atherosclerosis susceptibility. Female animals were placed on a 12-week Western diet startingat 6 weeks of age. Upon sacrifice animals were phenotyped for left common carotid artery lesion size and plasma lipid levels. Parental strain C57BL/6J-Apoetm1Unc displays significantly greater susceptibility to carotid artery atherosclerosis compared toparental strain C3H/HeJ-Apoetm1Unc/Wshi. Genome scan was performed using 143 polymorphic markers at a 12 cM resolution.
Significant linkage to carotid atherosclerosis, Cath1, mapped to 25 cM on mouse Chromosome 12 near D12Mit285 (LOD=4.5). This locusexplains 8% of the phenotypic variance. The 1-LOD support interval spans 21 cM - 28 cM. C57BL/6J-derived alleles at Cath1 confer increased carotid artery lesion area with an additive mode of inheritance.
Suggestive linkage to carotid atherosclerosis lesion size mapped to 58.5 cM on mouse Chromosome 1 near D1Mit45 (LOD=2.9), 64 cM on mouse Chromosome 5 near D5Mit210 (LOD=3.2), 38.5 cM on mouse Chromosome 6 near D6Mit102 (LOD=3.1), and 47.6 cM on mouse Chromosome 11 near D11Mit36 (LOD=2.4). Previously identified QTLs Artles (61 cM) and Athsq2 (62 cM) map near the chromosome 6 locus. C57BL/6J-derived alleles confer increased carotid artery lesion size with an additive mode of inheritance at loci on chromosomes 1, 6, and 11. The chromosome 5 locus exhibitsdominant inheritance with C3H/HeJ-derived alleles conferring increased lesion size.
Significant linkage to LDL/VLDL (LOD=10.1), HDL (LOD=7.2), and triglycerides (LOD=8.8) mapped to 92.3 cM on mouse Chromosome 1 near D1Mit270 and D1Mit406. C3H/HeJ-derived alleles confer increased levels of LDL/VLDL (dominant), HDL (additive), and triglycerides (dominant). This locus may be identical to previously identified QTL Hdlq15 (104 cM).
12.10.2014 Curator Note: Because Hdlq15 was originally mapped in J:88486 in 2004 using an (C57BL/6J x 129S1/SvImJ)F2 intercross, which differs from the cross used here, we consider the current study a separate mapping experiment and have named this QTL Hdlq86.
A novel QTL for non-HDL cholesterol mapped to 38 cM on mouse Chromosome 9 near D9Mit274 (LOD=2.7). This locus is named Nhdlq11. C3H/HeJ-derived alleles at Nhdlq11 confer increased LDL/VLDL and triglycerides with dominant inheritance. Nhdlq11 accounts for 5% of the LDL/VLDL variance and 5% of the triglyceride variance.
A novel QTL for non-HDL cholesterol, Nhdlq12, mapped to 47 cM on mouse Chromosome 12 near D12Mit97 (LOD=4.6). C57BL/6J-derived alleles at Nhdlq12 confer increased LDL/VLDL cholesterol with additive inheritance. Nhdlq12 accounts for 8% of the trait variance.
Suggestive linkage to LDL/VLDL levels mapped to 19.2 cM on mouse Chromosome 3 near D3Mit21 (LOD=2.7). This locus colocalizes with previously identified QTL Hdl5. C57BL/6J-derived alleles confer increased LDL/VLDL with additive inheritance.
Pnhdlc1 on Chromosome 6 was detected in this study at 30.4 cM near D6Mit243 (LOD=2.7) in linkage to LDL/VLDL levels. C57BL/6J-derived alleles confer increased LDL/VLDL with additive inheritance.
12.31.2014 Curator Note: Because Pnhdlc1 was originally mapped inJ:94547 in 2003 using a (CASA/RkJ x C57BL/6J)F2 intercross, which differs from the cross used here, we consider the current study a separate mapping experiment and have named this QTL Pnhdlc6.
Previously identified QTL Hdlq19 was detected in this study at 92cM near D2Mit263(LOD=4.3). C57BL/6J-derived alleles at Hdlq19 confer increased HDL cholesterol with dominant inheritance.
12.10.2014 Curator Note: Because Hdlq19 was originally mapped in J:88486 in 2004 using an ((C57BL/6J x 129S1/SvImJ)F2 intercross which differs from the cross used here, we consider the current study a separate mapping experiment and have named this QTL Hdlq91.
Linkage to HDL cholesterol mapped to 55.7 cM on mouse Chromosome 17 near D17Mit244 (LOD=3). This locus overlaps withpreviouslyidentified QTLs Hdl4 and Hdlq39. C57BL/6J-derived alleles confer increased HDL cholesterol with dominant inheritance.
12.10.2014 Curator Note: Because Hdlq39 was originally mapped in J:112688 using meta data from combined crosses, which differsfrom thecross used here, we consider the current study a separate mapping experiment and have named this QTL Hdlq94.
Linkage to triglycerides colocalized with Lprq4 at D5Mit95 (68 cM, LOD=3.2). C3H/HeJ-derived alleles confer increased triglyceride levels at this locus.
04.13.2015 Curator's Note: Because the QTL identified here as colocalizing with Lprq4 is a unique triglyceride QTL, we have named it Trigq4.
A novel triglyceride QTL mapped to 92 cM on chromosome 2 near D2Mit263 (LOD=2.5). This locus explains 6%of the phenotypic variance and the 1-LOD support interval spans 89 cM - 103 cM. C3H/HeJ-derived alleles confer increased triglyceride levels with dominant inheritance. This QTL has not yet been named.
Linkage to triglycerides colocalized with Trigq1 on mouse Chromosome 9 (38 cM, LOD=2.5). C3H/HeJ-derived alleles at this locus confer increased triglyceride levels with a dominant mode of inheritance.
04.13.2015 Curators Note: Because Triqg1 was originally mapped in 2003 in J:87328 using an (C57BL/6J x KK-Ay)F2 cross, which differs from the cross used here, we consider this a separate map study and have named this QTL Trigq3.