Linkage analysis was performed on 305 (PERA/EiJ x I/LnJ)F2 and 324 (PERA/EiJ x DBA/2J)F2 intercross animals to identify QTLs associated with lipoprotein cholesterol phenotypes. In the (PERA/EiJ x I/LnJ)F2 population 105 microsatellite markers at an average resolution of 16 cM were used, and in the (PERA/EiJ x DBA/2J)F2 population 98 microsatellite markers at an average resolution of 17.1 cM were used for the genome scan. Animals were fed a high fat diet for 8 weeks before phenotype analysis. Parental strain PERA/EiJ exhibits increased HDL cholesterol compared to I/LnJ and DBA/2J after 8 weeks on the high fat diet, while parental strain I/LnJ exhibit increased non-HDL cholesterol compared to PERA/EiJ and DBA/2J. Males typically exhibit higher HDL cholesterol than females, except in the PERA/EiJ inbred strain. Non-HDL cholesterol is typically increased in males except for inbred strain DBA/2J where levels are equal in males and females. A correlation between high lipoprotein cholesterol and gallstone formation was observed in the (PERA/EiJ x DBA/2J)F2 cross.
Hdlq33 (HDL QTL 33) mapped to 84 cM on mouse Chromosome 1 in the (PERA/EiJ x DBA/2J)F2 cross with LOD=6.5. The QTL interval spans 78 cM - 92 cM. This locus colocalizes with Hdlq5 (85 cM) and is syntenic to human Chromosome 1q23-q25.
Significant linkage to HDL cholesterol mapped to Chromosome 4 in both F2 crosses. This locus is the same as Hdlq10 (HDL QTL 10).
12.09.2014 Curator's Note: Because Hdlq10 was originally mapped in J:83460 in 2003 using a (CAST/Ei x DBA/2J)F2 cross, which differs from both of the crosses used here, we consider each cross a separate map experiment mapping novel QTL.
The QTL identified in the (PERA/EiJ x I/LnJ)F2 cross on Chromosome 4, mapping to 20cM, 95% confidence level spanning 8cM - 42cM, with a LOD=3.2, has been named Hdlq83.
The QTL identified in the (PERA/EiJ x DBA/2J)F2 cross on Chromosome 4, mapping to 22cM, 95% confidence level spanning 12cM - 40cM, and a LOD=3.4, has been named Hdlq84.
PERA/EiJ- derived alleles at both QTL confer increased HDL cholesterol; and are syntenic to human Chromosome 9p21. Abca1 at 23.1 cM is a positional candidate gene. Mutations in ABCA1 results in Tangier's disease in humans, which is associated with very lowlevels of HDL cholesterol.
Significant linkage to HDL cholesterol mapped to proximal mouse Chromosome 5 near D5Mit145 (0 cM) in the (PERA/EiJ x I/LnJ)F2 cross with LOD=5.6. This locus is named Hdlq34 (HDL QTL 34) and the 95% confidence interval spans 0cM-8cM.PERA/EiJ-derived alleles at Hdlq34 confer increased non-HDL cholesterol. Hdlq34 is syntenic to human Chromosome 7q11-q22.
Hdlq35 (HDL QTL 35) mapped to 42 cM on mouse Chromosome 6 in the (PERA/EiJ x I/LnJ)F2 cross with LOD=3.0. Hdlq35 is also significantlyassociatedwith gallstoneformation in both F2 crosses. The QTL interval spans 32 cM - 54 cM. This locus colocalizes with Hdlq11 (46 cM) and is syntenic to portions of human Chromosome 2p, 3p, 10p, and 12p.
Significant linkage to HDL cholesterol mapped to 28 cM onmouse Chromosome 11 in the (PERA/EiJ xI/LnJ)F2 cross with LOD=3.5. This locus is named Hdlq37 (HDL QTL 37). The QTL interval spans 8 cM - 52 cM. PERA/EiJ-derived alleles at Hdlq37 confer increased HDL cholesterol. Hdlq37 is syntenic to human Chromosome 5q35.