Experiment
90 female animals from an (SM/J x NZB/BlNJ)F1 x NZB/BlNJ backcross population were screened for an initial set of 78 SSLP markers to identify QTLs associated with HDL cholesterol (HDL-C) concentrations. Parental strain NZB/BlNJ exhibits elevated HDL-C onboth a CHOW and atherogenic diet compared to parental SM/J and F1 hybrid animals. A QTL linked to HDL-C on a CHOW diet, Hdlq1, peaked at 65 cM on mouse Chromosome 5 near D5Mit370 (LOD=2.7). NZB-derived alleles confer increased HDL cholesterol concentrations at Hdlq1. Scarb1 was identified as a viable candidate gene, but expression analysis did not reveal a difference in protein or mRNA levels between SM/J and NZB/BlNJ on CHOW or atherogenic diets. Sequence analysis detected a single nucleotide polymorphism between the 2 strains that does not result in an amino acid change. Therefore, Scarb1 is not likely to be the gene underlying Hldq1. A QTL linked to HDL-C on an atherogenic diet, Hdlq2, also mapped to mouse Chromosome 5 and peaks at 45 cM near D5Mit239(LOD=3.6). NZB-derived alleles confer increased HDL-C concentrations at Hdlq2. Both Hdlq1 and Hdlq2 were detected in linkage to HDL-C in previous QTL studies of different crosses such as (NZB/BlNJ x SM/J)F2, (CAST/Ei x C57BL/6J)F2, and (C57BL/6J x C3H/HeJ)F2. Suggestive loci were also detected near D6Mit44 (48 cM) and D18Mit24 (18 cM) in linkage to inducible HDL-C, and on mouse Chromosome 11 at 14 cM and 44 cM in linkage to non-HDL-C on a CHOW diet and non-HDL-C on an atherogenic diet, respectively.
Analysis Tools