Weighted single-step genome-wide association study and functional enrichment analyses for gastrointestinal nematode resistance traits in Santa Ines sheep

Nedenia Bonvino Stafuzza; Ana Claudia de Freitas; Marina B Mioto; Rafael Medeiros de Oliveira Silva; Breno de Oliveira Fragomeni; Victor Breno Pedrosa; Ricardo Lopes Dias da Costa; Claudia Cristina Paro de Paz

doi:10.1016/j.vetpar.2023.110047

Weighted single-step genome-wide association study and functional enrichment analyses for gastrointestinal nematode resistance traits in Santa Ines sheep

Vet Parasitol. 2023 Oct 7:323:110047. doi: 10.1016/j.vetpar.2023.110047. Online ahead of print.

Authors

Nedenia Bonvino Stafuzza¹, Ana Claudia de Freitas², Marina B Mioto³, Rafael Medeiros de Oliveira Silva⁴, Breno de Oliveira Fragomeni⁵, Victor Breno Pedrosa⁶, Ricardo Lopes Dias da Costa⁷, Claudia Cristina Paro de Paz³

Affiliations

¹ Sustainable Livestock Research Center, Animal Science Institute, 15130-000 São José do Rio Preto, SP, Brazil. Electronic address: nedeniabs@gmail.com.
² São Paulo Agency of Agribusiness and Technology, Animal Science Institute, 13380-011 Nova Odessa, SP, Brazil; Agricultural Research Agency of the State of Minas Gerais, 38709-899 Patos de Minas, MG, Brazil.
³ Sustainable Livestock Research Center, Animal Science Institute, 15130-000 São José do Rio Preto, SP, Brazil.
⁴ Zoetis, 04710-230 São Paulo, SP, Brazil.
⁵ Department of Animal Science, University of Connecticut, 06269 Storrs, CT, USA.
⁶ Department of Animal Science, State University of Ponta Grossa, 84030-900 Ponta Grossa, PR, Brazil.
⁷ São Paulo Agency of Agribusiness and Technology, Animal Science Institute, 13380-011 Nova Odessa, SP, Brazil.

PMID: 37857178
DOI: 10.1016/j.vetpar.2023.110047

Abstract

This study aimed to identify genomic regions, pathways, and putative candidate genes associated with resistance to gastrointestinal nematode in Santa Ines sheep. The phenotypic information comprised 5529 records from 1703 naturally infected animals. After genomic data quality control, 37,511 SNPs from 589 animals were available. The weighted single-step approach for genome-wide association study was performed to estimate the SNP effects and variances accounted by 10-SNP sliding windows. Confirming the polygenic nature of the studied traits, 20, 22, 21, and 19 genomic windows that explained more than 0.5% of the additive genetic variance were identified for fecal egg counts (FEC), Famacha© (FAM), packed cell volume (PCV), and total plasma protein (TPP), respectively. A total of 81, 122, 106, and 101 protein-coding genes were found in windows associated with FEC, FAM, PCV, and TPP, respectively. Several protein-coding genes related to the immune system and inflammatory response functions were identified within those genomic regions, such as ADCY9, ADRB2, BRAF, CADM1, CCL20, CD70, CREBBP, FNBP1, HTR4, IL16, IL22, IL26, MAPK8, NDFIP1, NLRC3, PAK5, PLCB1, PLCB4, ROCK1, TEK, TNFRSF12A, and VAV1. Functional enrichment analysis by DAVID tool also revealed many significant (P < 0.05) pathways and Gene Ontology terms that could be related to resistance to gastrointestinal nematode in Santa Ines sheep, such as chemokine signaling pathway (oas04062), cAMP signaling pathway (oas04024), cGMP-PKG signaling pathway (Oas04022), platelet activation (Oas04611), Rap1 signaling pathway (oas04015), and oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705). These results contribute to improving the knowledge of the genetic architecture of resistance to gastrointestinal nematode in Santa Ines sheep.

Keywords: Genomic regions; Haemonchus; Ovis aries; Parasites resistance; WssGWAS.