Genome-Wide Association Study Based on Pathways Analysis for Detection Candidate Genes Related to Hematological Traits in Sheep
2022
Mohammadi, Hossein | Najafi, Abouzar | Shamsollahi, Mohammad
BACKGROUND: Red blood cells play an essential role in the oxygen transport and the immune system. Moreover, hematologic parameters are an important clinical indicator of various diseases including anemia and metabolic syndrome.OBJECTIVES: The present study aimed to conduct genome-wide association studies (GWAS) based on gene-set enrichment analysis to identify the loci associated with hematological traits using 630K arrays.METHODS: For this purpose, the phenotype records included 498 genotyped Alpine Merino sheep were used for red blood cell count (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and RBC volume distribution width coefficient of variation (RWD_CV). Genome-wide association study was performed with hematological traits using TASSEL software. Using biomaRt2 R package R, SNP was assigned to genes. GO, KEGG, DAVID, and PANTHER databases were used to assign the genes to functional categories.RESULTS: 11 SNP markers on chromosomes 1, 2, 3, 6, 8, 10, 11, 14, and 20 located in TRPC4, SPAT1, TMCC2 (RBC), KRT26, GPLD1, EPAS1 (HGB), RAC2, HSPD1, PDGFRA (HCT) and BBS1, HAG1, PIK3R3, STXBP5, FCER1G (MCH, MHCH, RWD_CV) genes were identified. Based on the pathway analysis, 17 pathways from gene ontology and biological pathways were associated with hematological traits (P˂0.05). The pathways have important functions in the development and differential of red blood cells, hypoxia, adaptation process, environmental stress, and platelet activation.CONCLUSIONS: In total, this study supported previous results from the GWAS of hematological traits, and also revealed additional regions in the sheep genome associated with important traits, using these findings could be potentially useful for genetic selection in the breeding programs.
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