Experiment
To identify loci that influence lipo-protein cholesterol levels QTL mapping was performed on PERA/EiJ x I/LnJ and PERA/EiJ x DBA/2J intercrosses and in a combined data set from both crosses. 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 exhibits increased non-HDL cholesterol compared to PERA/EiJ and DBA/2J.
LOD scores for HDL cholesterol concentrations were considered significant when exceeding 2.9in each of the PERA intercrosses.
A LOD score of 3.0 or better was the threshold for significance in the combined cross data when the cross was an additive covariate; 3.7 when the cross was an interactive covariate.The analysis of combined data from bothcrosses increased the detection power of the analysis and identified additional significant loci for HDL cholesterol levels on Chromosomes 7, 15 and 16.
The chromosome 7 QTL, labeled Hdlq36, achieved a LOD score of 2.7 in the (PERA/EiJ x I/LnJ) F2 cross and 0.7 in the (PERA/EiJ x DBA/2J)F2 cross. In the combined cross analysis, using cross as an interactive covariate, the LOD score was 4.7, peaking between 68 - 74 cM. This interval on mouse chromosome 7 is homologous with human regions: 1p15, 11q13-14, 16q11-12 and 10q26. [Table 3].
Chol1 (65 cM) is a previously identified cholesterol QTL located near Hdlq36.
The Chromosome 15 QTL, labeled Hdlq38, achieved a LOD score of 2.3 in the (PERA/EiJ x I/LnJ)F2 cross and 0.7 in the (PERA/EiJ x DBA/2J)F2 cross.In the combined cross analysis, using cross as an interactive covariate, the LOD score was 4.6, peaking between 32 - 62 cM. This interval on mouse chromosome 15 is homologous with human regions: 18q24, 12q12-13; and 22q12-13. [Table 3]. Hdlq27 (48 cM)and Lipq3 (49.6 cM) colocalize with Hdlq38
The Chromosome 17 QTL, labeled Hdlq39, achieved a LOD score of 1.6 in the (PERA/EiJ x I/LnJ)F2 cross and 1.6 in the (PERA/EiJ x DBA/2J)F2 cross. In the combined cross analysis, using cross as an interactive covariate, the LOD score was 3.7, peaking between 42-58 cM. This interval on mouse chromosome 17 is homologous with human regions: 2p23-16, and 18.p11 [Table 3].