Genome-wide Association Study Identifies Candidate Susceptibility Loci For Pig Inguinal/Scrotal Hernias

Pig inguinal/scrotal hernias are one of the most common congenital disorders in pigs and cause severe economic loss in the pig industry. Pigs develop inguinal/scrotal hernias with a prevalence of1%and estimated heritabilities between0.2and0.6in different breeds and environment. It is difficult to decrease the occurring frequencies of pig inguinal/scrotal hernias by traditional phenotype selection in the breeding schemes. Identification of causative genes or closely Linkage Disequilibrium markers for inguinal/scrotal hernias is an essential precondition for removal of this genetic defect by marker-assisted selection(MAS).We herein collected739commercial pubred pigs representing Landrace, Large White, Duroc and Pietrain breeds with239inguinal/scrotal individual cases and their unaffected siblings in222families from16commercial pig breeding farms in8provinces in China All animals were genotyped with Illumina porcine60k DNA chips. After quality control, a total of39289SNPs and711samples including226inguinal/scrotal case animals from211families were used for genome-wide association analysis.To avoid population stratification effect on GWAS, we analyzed population structures. Transmission disequilibrium test (TDT) and QQ-plots of the P values analysis were first implemented to identified candidate susceptibility loci for pig inguinal/scrotal hernias, however no significant locus was detected. Genome-wide linkage analysis of inguinal/scrotal hernias were then conducted separately and collectively in3half-sib families each with more than7inguinal/scrotal case animals. Again,we failed to identify significant locus. Lastly, we performed the case-control genome-wide analysis based on single-maker and haplotype by using Q-Q plots for veridation. Five susceptibility loci in a region of17.83-18.13Mb on SSC1including ASGA0097745, ASGA0001418, ASGA0001422, ALGA0001427, and H3GA0001012, and one SNP at16.85Mb on SSC7, showed significant association with pig inguinal/scrotal hernia. Of these loci, ASGA0097745is the most significant with a P value of0.00057.This results confirmed the previous finding on SSC1,while the locus on SSC7was reported for the first time.Two positional candidate genes, UST and CDKAL1, were found from these two susceptibility regions using Ensembl website. The UST gene on SSC7is a more promising candidate gene affecting pig inguinal/scrotal hernia for its function on biosynthesis of dermatan sulfate glycosaminoglycan, which has been shown to be associated with human syndromes with phenotype of hernia. While CDKAL1(cyclin-dependent kinase5regulatory subunit associated protein1-like1) could affect the occurrence of hernia through the function on cell death. Further study should be directed to validate the above-mentioned candidate region and genes for pig scrotal/inguinal hernia by larger population&deep GWAS strategies.In summary, this study identified two susceptibility loci for pig inguinal/scrotal hernia by GWAS.The findings paved the load to fine mapping the two loci of interest, and to develop molecular breeding technologies for selections against inguinal/scrotal hernia in pigs.