Genetic Arehitechture Of Serum Lipid Traits In Pigs

Serum lipids widely exist in animals and are the necessary materials in the foundationof cell metabolism, which are associated with cardiovascular disease, obesity, metabolismsyndrome and diabetes. Hence, Serum lipids including total cholesterol (TC), low densitylipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) andtriglyceride (TG) are used as clinical diagnostic indexes to determine whether the serumlipids are abnormal on the related illnesses. In our previous study, we identified asignificant region on SSC2and SSC3associated with serum lipid traits in a White Duroc×Erhualian F2resource population and Sutai pigs.To further dig out the significant chromosomal region associated with serum lipidtraits, we chose Chinese native Laiwu pigs as the research object because of the obviousfeature on the fat deposition. All animals were genotyped using Porcine SNP60BeadChips.Then, GWAS was performed for serum lipid traits. We found that a total of73SNPsachieved chromosomal significance threshold of P<2.02×10-5(1/49,442), corresponding to5chromosomes (1,3,5,12and13). Some regions were associated with several blood serumlipid traits, of which43achieved genome-wide significance levelP<1.01×10-6(0.05/49,442). MARC0083986, which was the most prominent associationwith LDL-C and TC, was identified on SSC3:125,211,999bp explained23.77%and16.00%of LDL-C and TC phenotypic variation, respectively. All of them were mapped to118.61Mb~131.79Mb region on SSC3except one SNP (ALGA0115386) which did notlocate on the specific chromosome.42SNPs were significantly associated with LDL-C,contained all of the22SNPs influenced TC. In addition, we found the important candidategenes around the most significant SNP region, such as, APOB and NCOA1gene in theregion (118.61Mb~131.79Mb) on SSC3and the COQ10A and APOF gene associated withHDL-C/LDL-C on SSC5. Meanwhile, the Meta analysis was carried out in fivepopulations (White Duroc×Erhualian F2intercoss, Sutai pigs, Duroc×Landrace×LargeWhite, Laiwu pigs and Erhualian population). By the way, we found some new SNPs onSSC1, SSC9and SSC12, which were associated with HDL-C/LDL-C, HDL-C and TC, andwe also found some new important candidate genes such as CILP2, LIPG and ACAA2gene.In our previous study, a1%genome-wide significant QTL for LDL-C and TC wasidentified around LDLR gene on SSC2in a White Duroc×Erhualian F2resourcepopulation (Chen et al.2009). In our further GWAS study (Chen et al.2013), this QTLwas found the most predominant effect on LDL-C and TC in Sutai pigs. To separate themajor gene and the causal mutation in the QTL region, we systematically assessed the associations of LDLR with LDL-C and TC in the three populations (Sutai pigs, WhiteDuroc×Erhualian F2resource population and Duroc×Landrace×Large Whitepopulation). Firstly, we used the DNA from six individuals which had extremelyphenotypic traits in Sutai pigs and Duroc×Landrace×Large White population,respectively, as templates to search all the exons. We identified a total of10SNPsincluding2missense mutations and8synonymous mutations. Furthermore, the standardassociation analysis, F-drop value and haplotype-based association were used to analysethe association between the missense mutaions and LDL-C and TC. In Sutai pigs, theresults showed c.1812C>T was the strongly associated with LDL-C and TC (adjust P=5.40×10-11and P=3.64×10-8), showing that the SNPs had close linkage with major loci ofQTL at least, and could be the causal mutation cite. Moreover, it explained all the QTLeffect in the F-drop test. The significance was the strongest between the SNP of haplotypeand LDL-C and TC, explaining all the phenotypic variation of QTL in Sutai pigs. All theresults suggested the c.1812C>T is the strong causal candidate to QTL for LDL-C and TCin the Sutai pigs. However, the strong effect between c.1812C>T and LDL-C and TC wasnot in the other two populations due to the fact that it has no such cite in White Duroc×Erhualian F2resouce population or very low polymorphism in Duroc×Landrace×LargeWhite population (0.74%). Hence, heterogeneity exists in different populations of the QTLon SSC2which affects LDL-C and TC.