{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T02:24:08Z","timestamp":1789957448252,"version":"4.0.1"},"reference-count":68,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation project of Shandong Province","award":["ZR2023QC044"],"award-info":[{"award-number":["ZR2023QC044"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32402725"],"award-info":[{"award-number":["32402725"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Project of Improved Agricultural Varieties in Shandong Province","award":["2021LZGC010"],"award-info":[{"award-number":["2021LZGC010"]}]},{"name":"Shandong Provincial Sheep and Goat Industry Technology System","award":["SDAIT-10-01"],"award-info":[{"award-number":["SDAIT-10-01"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Gastrointestinal nematode infections represent a major constraint to sheep production globally, with widespread drug resistance requiring alternative control strategies. Methods: This systematic review combined genome-wide association study findings to understand the genetic basis underlying parasite resistance traits in sheep. Following PRISMA guidelines, we identified 22 studies including 28,033 samples from 32 breeds across 11 countries, extracting 1580 candidate genes associated with resistance traits, including fecal egg count, packed cell volume, and immunoglobulin levels. Gene prioritization analysis using ToppGene identified 75 high-confidence candidate genes. Results: Functional enrichment analysis revealed significant involvement of the JAK-STAT signaling pathway, inflammatory response processes, and immune-related biological functions. Protein\u2013protein interaction network analysis identified nine key hub genes: TNF, STAT3, STAT5A, PDGFB, ADRB2, MAPT, ITGB3, SMO, and GH1. The JAK-STAT pathway emerged as particularly important, with multiple core genes involved in cytokine signaling and immune cell development. These findings demonstrate that parasite resistance involves complex interactions between inflammatory responses, immune signaling networks, and metabolic processes. Conclusions: This comprehensive genetic framework provides essential insights for developing genomic selection strategies and marker-assisted breeding programs to enhance natural parasite resistance in sheep, offering a sustainable approach to reducing drug dependence and improving animal welfare in global sheep production systems.<\/jats:p>","DOI":"10.3390\/genes16101151","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:00:32Z","timestamp":1759132832000},"page":"1151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Candidate Genes of Gastrointestinal Nematode Resistance Traits in Sheep: A Systematic Review of GWASs and Gene Prioritization Analysis"],"prefix":"10.3390","volume":"16","author":[{"given":"Zhirou","family":"Zhang","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong Provincial Animal Husbandry Station (Shandong Province Breeding Livestock and Poultry Quality Measuring Station), Jinan 250100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deji","family":"Xu","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueqi","family":"Ma","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianlong","family":"Wang","sequence":"additional","affiliation":[{"name":"Jinan Animal Disease Prevention and Control Center, Jinan 250022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"Jinan Animal Husbandry Technology Extension Station, Jinan 250300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Hou","sequence":"additional","affiliation":[{"name":"Tai\u2019an Animal Husbandry and Veterinary Service Center, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8753-4034","authenticated-orcid":false,"given":"Jiaqing","family":"Hu","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9721-0634","authenticated-orcid":false,"given":"Tianle","family":"Chao","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0304-4017(03)00204-8","article-title":"Modeling of host genetics and resistance to infectious diseases: Understanding and controlling nematode infections","volume":"115","author":"Bishop","year":"2003","journal-title":"Vet. 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