Identification of Selection Signatures Related to Johne's Disease in Iranian Holstein Cows using Genomic Data

Background : One of the principal and challenging animal studies in population genetics is to identify the signs of selection to improve economic traits and reduce diseases.Johne's disease is an incurable chronic bacterial infection that primarily affects the lower parts of the small intestine of ruminants, although its pathology and symptoms vary among species.The economic consequences of Johne's disease include reduced production, loss of genetic value, increased sensitivity to other diseases, increased interval between calving, weight loss, reduced carcass value, reduced fertility (due to reduced serum progesterone formation and corpus luteum), decreased quality and quantity of milk (decreasing fat and protein and increasing somatic cells in milk), and premature elimination.According to the results of new research, this bacterium may be a zoonotic pathogen that plays a role in causing Crohn's disease (a chronic inflammatory bowel disease (IBD)) in humans.Even after milk pasteurization, this pathogen remains alive and is therefore a threat to the health of society.This disease is one of the main diseases economically and one of the most prevalent diseases, causing great economic damage to the livestock industry worldwide.In this study, an extensive genome-wide scan was performed using single nucleotide polymorphisms (SNPs) to identify the signs of selection between populations of Holstein cows affected by Johne's disease and healthy animals.Methods: In this study, 145 Holstein cows of the Feka cattle farm in Isfahan were genotyped based on Illumina 30K chips.Cows were grouped into two sick and healthy groups, with 45 and 100 cows, respectively.Quality control indicators included the animal read rate (mind), SNP read rate (geno), rare allele frequency (MAF), and Hardy-Weinberg equilibrium.To identify important metabolic pathways, ClueGo (version 2.5.6) was used in Cytoscape software, which provides biological interpretations of genes.In this study, two statistics, iHS and RSB, were used to identify the signs of selection.Results: Using iHS statistics, 63 and 70 genes were identified in the diseased and healthy populations of Holstein cows, respectively.The important genes identified by iHS statistics included HCN2, DOCK4, ITGA8, and STAG1 in the patient population, and CAV2, CNTNAP4, MIB1, and TTC23 in the healthy population.After examining the selected regions, 39 and 53 genes were identified in the diseased and healthy populations of Holstein cows with RSB statistics.The important genes identified by RSB statistics included GRID2, PPIP5K2, and CTNNA2 in the patient population, and DOCK1, PCDH9, and AK1 in the healthy population. Conclusion:In the present study, the results of the iHS statistics showed that 84 and 96 genomic regions were under selection in the healthy and patient populations, as well as 152 and 129 genomic regions in the healthy and patient populations using the RSB statistics.Most of the genes identified in this study were related to immunity, cancer, bacterial invasion of cells, cell aging,