Nucleotide Sequence and Association Analysis of Pig Apolipoprotein-B and LDL-Receptor Genes

Three genes are the major determinants of heritable hypercholesterolemia diseases in humans: APOB, LDLR and LDLRAP1, which encode for proteins that physically interact to promote cholesterol uptake in the cell. We have carried out association analyses of these variants with serum cholesterol and triglycerides concentrations in a half-sib Duroc pig population. Given the structure of the population (six paternal half-sib families), we have used a statistical model that considers separately the allele transmission through dams (at population level) and through sires (within-families from heterozygous sire). Only polymorphisms showing a relevant substitution effect for both male- and female-transmitted alleles are likely to be causal mutations. Thus, although we have found statistical association between genotypes for LDLR and APOB polymorphisms and serum lipid levels (mean allele substitution effects ranging from 15 to 40% of the standard deviation of these traits), none of them seem to be the causal mutation but probably represent closely linked polymorphisms. We have shown here that these three genes also contribute to genetic variability in pigs, with the description of new polymorphisms in their coding regions. Moreover, we have demonstrated that variants on two of these three genes are segregating in a number of commercial breeds. Finally, we report here the coding region for the porcine LDLRAP1 gene and describe a polymorphism in the last exon of this gene.