Multiple association studies identify 3 novel candidate genes for teat number trait in Danish Landrace and Large White pigs: BRINP3, LIN52, and UBE3B.

Milk is an essential source of nutrition for preweaning piglets. Therefore, in the breeding process, sows were expected to have sufficient teats to suckle their piglets. However, in Danish Landrace and Large White pigs, the number of piglets born currently exceeds the number of teats, making it urgent to select and breed for an increased teat number. In this study, the samples of 491 Danish Landrace pigs and 1,047 Danish Large White pigs with teat number phenotype were used to perform genome-wide association studies to identify SNPs associated with total teat number (TTN) based on SNP-chip data and data imputed to the level of whole-genome sequencing (iWGS), respectively. In Landrace pigs, the most significant SNP on SSC10 explains 5.14% of the phenotypic variance, while in Large White pigs, the most significant SNP on SSC7 explains 4.46% of the phenotypic variance. Additionally, linkage disequilibrium and linkage analysis (LDLA) were used to refine the regions of QTLs on SSC10 to 2.89 to 5.43 Mb in Danish Landrace pigs and to 96.00 to 97.95 Mb on SSC7 in Danish Large White pigs, respectively. To maximize the utility of information from 2 populations, meta-analysis was conducted across multiple populations. A total of 12 protein-coding genes were identified within the candidate QTL regions determined by LDLA and meta-analysis. To supplement the candidate gene set, transcriptome-wide association studies (TWAS) based on embryo and placenta tissues identified 7 protein-coding genes associated with TTN in Landrace and Large White pigs. Phenome-wide association studies (PheWAS) query was conducted for all the above genes, revealing that nearly all of them are associated with teat number traits. Additionally, some genes showed strong associations with carcass traits, suggesting a potential association between teat number and carcass traits. Through functional annotation and integrated analysis, BRINP3, LIN52, ABCD4, and UBE3B were determined as the functional candidate genes regulating TTN. These findings lay the foundation for identifying the genetic loci regulating teat number in Danish pigs, as well as for their molecular breeding.