Imputed whole genome sequence based association pinpoints genetic architecture of labour dystocia of pigs using multi-breed populations

Abstract

Abstract Background Labour dystocia (LAD) in sows is a common reproductive disorder that reduces piglet survival rates and increases the number of stillbirths, causing substantial economic losses to pig farms. However, the genetic basis of LAD remains elusive. Herein, we performed a single-breed genome-wide association study (GWAS) for LAD using imputed whole-genome sequence data from 3263 sows (487 Landrace and 2776 Yorkshire). Results In this study, analysis of the reproductive traits showed that the total number of piglets born and the number of piglets born alive were 1.43–2.85 and 1.60–2.94 higher, respectively, in sows with natural labour than in those with LAD. We identified 250 and 12 SNPs associated with LAD in primiparous and multiparous sows, respectively. Furthermore, in primiparous Yorkshire sows, two major QTL were fine-mapped to a 498.44 kb interval (23.18–23.68 Mb) on SSC2 and a 779.85 kb interval (43.34–44.12 Mb) on SSC9. Further analysis revealed that the two significant SNPs (2_23340612 and 9_44119733) within these QTL regions were located within regulatory regions across multiple pig breeds and tissues. The potentially regulatory SNP (2_23340612) is located within the binding sites of 27 transcription factors, that are primarily involved in oxytocin signalling, muscle contraction, and the development of female genitalia and embryo. The other potentially regulatory SNP (9_44119733) is located within the binding sites of eight transcription factors, among which three transcription factors (ZNF274, HMGA1, and CTCF) are predicted to interact with six candidate genes ( APOA1 , APOC3 , APOA4 , APOA5 , BUD13 , and ZPR1 ). Finally, eight promising candidate genes ( APOA1 , APOC3 , APOA4 , APOA5 , BUD13 , ZPR1 , ACAN , and HAPLN3 ) were identified to be associated with LAD. Functional enrichment analysis indicated that the candidate genes were enriched in pathways related to lipid metabolism, extracellular matrix organization, cell adhesion and response to estrogen. Conclusions The LAD is a prominent reproductive disorder trait that negatively impacts the reproductive efficiency of sows. This study identified potentially regulatory SNPs (2_23340612 and 9_44119733) and eight promising genes ( APOA1 , APOC3 , APOA4 , APOA5 , BUD13 , ZPR1 , ACAN , HAPLN3 ) associated with LAD. To our knowledge, this is the first whole-genome-sequence-based GWAS with large-scale reproductive data to identify genetic markers and candidate genes of LAD of sows.