Revealing new candidate genes for reproductive traits in pigs: combining Bayesian GWAS and functional pathways

Abstract

BackgroundReproductive traits such as number of stillborn piglets (SB) and number of teats (NT) have been evaluated in many genome-wide association studies (GWAS). Most of these GWAS were performed under the assumption that these traits were normally distributed. However, both SB and NT are discrete (e.g. count) variables. Therefore, it is necessary to test for better fit of other appropriate statistical models based on discrete distributions. In addition, although many GWAS have been performed, the biological meaning of the identified candidate genes, as well as their functional relationships still need to be better understood. Here, we performed and tested a Bayesian treatment of a GWAS model assuming a Poisson distribution for SB and NT in a commercial pig line. To explore the biological role of the genes that underlie SB and NT and identify the most likely candidate genes, we used the most significant single nucleotide polymorphisms (SNPs), to collect related genes and generated gene-transcription factor (TF) networks.ResultsComparisons of the Poisson and Gaussian distributions showed that the Poisson model was appropriate for SB, while the Gaussian was appropriate for NT. The fitted GWAS models indicated 18 and 65 significant SNPs with one and nine quantitative trait locus (QTL) regions within which 18 and 57 related genes were identified for SB and NT, respectively. Based on the related TF, we selected the most representative TF for each trait and constructed a gene-TF network of gene-gene interactions and identified new candidate genes.ConclusionsOur comparative analyses showed that the Poisson model presented the best fit for SB. Thus, to increase the accuracy of GWAS, counting models should be considered for this kind of trait. We identified multiple candidate genes (e.g. PTP4A2, NPHP1, and CYP24A1 for SB and YLPM1, SYNDIG1L, TGFB3, and VRTN for NT) and TF (e.g. NF-κB and KLF4 for SB and SOX9 and ELF5 for NT), which were consistent with known newborn survival traits (e.g. congenital heart disease in fetuses and kidney diseases and diabetes in the mother) and mammary gland biology (e.g. mammary gland development and body length).Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-016-0189-x) contains supplementary material, which is available to authorized users.

Genetic analysis of teat number in pigs reveals some developmental pathways independent of vertebra number and several loci which only affect a specific side

“…The concept that additional mammary glands arise from somite division in the developing embryo is supported by the effects of the VRTN gene that were observed on vertebra number and teat count [6, 12, 16, 17, 23] and of the NR6A1 gene on SSC1 [6]. However, since genetic variation within NR6A1 is only observed in crosses between Asian and European breeds, we were not able to evaluate this result.…”

“…Putative causative genetic variations for vertebra number in the NR6A1 gene [14] on SSC1 and the VRTN gene [15] on SSC7 have been associated with variation in teat number in Meishan × occidental cross populations [6, 12]. VRTN has also been associated with teat number in commercial swine populations [13, 16, 17]. …”

Genome-wide association study for conformation traits in three Danish pig breeds

“…In humans, it was shown that mutations in RIPPLY2 are associated with segment defects of the vertebrae [41]. In pigs, Verardo et al [42] reported that SYNDIG1L was associated with number of teats while Duijvesteijn et al [43] showed that number of teats and number of vertebras were controlled by several pleiotropic coding genes. These findings suggest that SYNDIG1L may have a role in the development of vertebrae in pigs.…”

Genome-wide association study and accuracy of genomic prediction for teat number in Duroc pigs using genotyping-by-sequencing

“…Another GWAS, using 32,911 SNPs on 1550 Large White pigs, reported 21 QTL with additive effects on chromosomes 6, 7 and 12, one QTL with a dominant effect on chromosome 4, and identified VRTN as the most promising candidate gene for teat number [3]. A third GWAS using 41,647 SNPs on 1657 Large White pigs found 65 significant SNPs on chromosomes 1, 2, 7, 8, 12 and 14, including SNPs in the region 102.9 between 105.2 Mb on chromosome 7 [4]. A fourth GWAS using 39,778 SNPs identified the VRTN gene with pleiotropic and desirable effects on thoracic vertebral number, teat number and carcass (body) length across four pig populations, and showed that, of all SNPs on chromosome 7, a SNP within the VRTN gene had the most significant effect on teat number in Duroc pigs [5].…”

“…A GWAS using the porcine 60 K SNP chip on a F2 population from a cross between Landrace and Korean pigs identified highly significant SNPs on chromosome 7 that were more than 40 Mb away from the VRTN gene [6], and in another GWAS using 36,588 SNPs and 1024 Duroc pigs, the most significant SNPs on chromosome 7 were found 2 to 3 Mb downstream of the VRTN region [7]. However, other than for the VRTN region, there is little consensus among the GWAS results on genomic regions that affect teat number [2–4, 6, 7]. Therefore, additional studies are needed to identify the genetic factors that affect swine teat number.…”