Whole-Genome Resequencing-Based Selection-Signal and Association Analyses Prioritize Candidate Genes and Haplotypes...

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRSV, causes substantial economic losses in the swine industry. Because viral variability and host genetic complexity limit conventional control, identifying host genetic factors associated with PRRS resistance through genomic approaches is important for disease-resistant breeding. In this study, 699 pigs were immunized with a PRRSV vaccine, 135 were selected for PRRSV infection experiments, and 133 were retained for whole-genome resequencing after two-stage phenotypic screening based on post-immunization and post-infection profiles. Genome-wide selection-signal analysis identified 12 highly differentiated regions (F_st > 0.15), annotated to 11 candidate genes: NFXL1, NIPAL1, CHIC2, LOC100623351, LOC100513671, LOC100513484, CENPC, STAP1, UBA6, GNRHR, and LOC100512727. The original exploratory GWAS identified candidate association signals, including signals annotated to PYGM, NFXL1, KIAA1324L, and FLNC; after PC1/PC2 adjustment, NFXL1 retained exploratory support, and additional exploratory signals were observed. Public PRRSV-related transcriptomic datasets provided additional expression-level evidence, with NIPAL1 and PYGM showing increased expression in PRRSV-infected porcine alveolar macrophages. Functional enrichment and variant-level analyses supported the biological relevance of the prioritized candidate gene set, particularly the chromosome 8 NFXL1 region, where the A-C-G haplotype was more frequent in resistant pigs. These findings provide useful genetic clues for further validation and PRRS resistance breeding.