Identification and association analysis of several hundred single nucleotide polymorphisms within candidate genes for back fat thickness in Italian Large White pigs using a selective genotyping approach1

Abstract

Combining different approaches (resequencing of portions of 54 obesity candidate genes, literature mining for pig markers associated with fat deposition or related traits in 77 genes, and in silico mining of porcine expressed sequence tags and other sequences available in databases), we identified and analyzed 736 SNP within candidate genes to identify markers associated with back fat thickness (BFT) in Italian Large White sows. Animals were chosen using a selective genotyping approach according to their EBV for BFT (276 with most negative and 279 with most positive EBV) within a population of ≈ 12,000 pigs. Association analysis between the SNP and BFT has been carried out using the MAX test proposed for case-control studies. The designed assays were successful for 656 SNP: 370 were excluded (low call rate or minor allele frequency <5%), whereas the remaining 286 in 212 genes were taken for subsequent analyses, among which 64 showed a P(nominal) value <0.1. To deal with the multiple testing problem in a candidate gene approach, we applied the proportion of false positives (PFP) method. Thirty-eight SNP were significant (P(PFP) < 0.20). The most significant SNP was the IGF2 intron3-g.3072G>A polymorphism (P(nominal) < 1.0E-50). The second most significant SNP was the MC4R c.1426A>G polymorphism (P(nominal) = 8.0E-05). The third top SNP (P(nominal) = 6.2E-04) was the intronic TBC1D1 g.219G>A polymorphic site, in agreement with our previous results obtained in an independent study. The list of significant markers also included SNP in additional genes (ABHD16A, ABHD5, ACP2, ALMS1, APOA2, ATP1A2, CALR, COL14A1, CTSF, DARS, DECR1, ENPP1, ESR1, GH1, GHRL, GNMT, IKBKB, JAK3, MTTP, NFKBIA, NT5E, PLAT, PPARG, PPP2R5D, PRLR, RRAGD, RFC2, SDHD, SERPINF1, UBE2H, VCAM1, and WAT). Functional relationships between genes were obtained using the Ingenuity Pathway Analysis (IPA) Knowledge Base. The top scoring pathway included 19 genes with a P(nominal) < 0.1, 2 of which (IKBKB and NFKBIA) are involved in the hypothalamic IKKβ/NFκB program that could represent a key axis to affect fat deposition traits in pigs. These results represent a starting point to plan marker-assisted selection in Italian Large White nuclei for BFT. Because of similarities between humans and pigs, this study might also provide useful clues to investigate genetic factors affecting human obesity.

Rab GAPs AS160 and Tbc1d1 play nonredundant roles in the regulation of glucose and energy homeostasis in mice

“…How AS160 and Tbc1d1 control body weight, energy expenditure, and fatty acid oxidation is currently not known. But Tbc1d1 mutations and single nucleotide polymorphisms are associated with body weight and body composition changes in animals (4,12,37,38) and with obesity in humans (16,20,23,31).…”

Analysis of Association Between a Microsatellite at Intron 1 of the Insulin-Like Growth Factor 1 (IGF1) Gene and Fat Deposition, Meat Production and Quality Traits in Italian Large White and Italian Duroc Pigs

“…Studies of CasasCarrillo et al (1997) and Assis de Faria et al (2009) based on microsatellite analyses (including the IGF1 short tandem repeat marker) indicated that this chromosome region harbours QTL for growth and carcass traits. However, previous genome wide association studies we conducted on Italian Large White pigs by using single nucleotide polymorphisms in a few hundred candidate genes and the Illumina PorcineSNP60 BeadChip tool did not show any marker significantly associated with BFT in the region of SSC5 located around IGF1 (Fontanesi et al, 2012b(Fontanesi et al, , 2012c. These results would indicate that no important segregating SSC5QTL, at least for BFT, might be present in this breed.…”

“…The first group of the selective genotyping approach was constituted by 560 Italian Large White gilts with no common parents, selected among ~12,000 performance tested pigs of this breed in the period 1995-2007 (Fontanesi et al, 2012b Fontanesi et al, 2008Fontanesi et al, , 2010 (Fontanesi et al, 2010).…”

Associations of fifty single nucleotide polymorphisms within candidate genes with meatness in pigs

“…On the other hand, an interaction among and within loci may also be shown in the ranking of chromosomes. Complex genetic determination of meatness has been reported by a number of authors (Kamiński et al, 2009;Srikanchai et al, 2010;Weisz et al, 2011;Fontanesi et al, 2012).…”