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 identifi ed 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 Pnominal 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 signifi cant (PPFP < 0.20). The most signifi cant SNP was the IGF2 intron3-g.3072G>A polymorphism (Pnominal < 1.0E-50). The second most signifi cant SNP was the MC4R c.1426A>G polymorphism (Pnominal = 8.0E-05). The third top SNP (Pnominal = 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 signifi cant 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, LAT, 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 coring pathway included 19 genes with a Pnominal < 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.
|Autori:||Fontanesi, L.;Galimberti, G.;Calò, D.G.;Fronza, R.;Martelli, P.L.;Scotti, E.;Colombo, M.;Schiavo, G.;Casadio, R.;Buttazzoni, L.; Russo, V.|
|Data di pubblicazione:||2012|
|Titolo:||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 approach|
|Rivista:||JOURNAL OF ANIMAL SCIENCE|
|Appare nelle tipologie:||1.1 Articolo in rivista|