Genome-wide association study to identify genomic regions associated with Johne's disease in Iranian Holstein cattle

Paratuberculosis  known as Johne's disease, is a contagious, chronic, intestinal disease in ruminants, which is caused by Mycobacterium avium paratuberculosis subspecies (MAP) and causes a huge economic damage to the livestock industry. There is no effective treatment nor vaccine for MAP infection. Thus, investigating the genetic regions associated with susceptibility to MAP infection can provide a better understanding of paratuberculosis mechanisms and contribute to the genetic improvement of animals. The aim of this study was to identify genomic regions and candidate genes associated with susceptibility to MAP infection in Holstein dairy cattle using a genome-wide association study (GWAS). For this purpose, blood samples of 150 cows were collected, and DNA and serum of them were extracted.The prepared DNA samples were genotyped using bovine SNPchip30k (Illumina). Quality control of genotypes was performed based on the minor allele frequency (PMAF < 0.05), missing genotype (PMIND > 0.05), genotyping rate (PGENO > 0.05), and Hardy-Weinberg equilibrium (PH-W < 1) 10-6) using PLINK software. The association was performed using a mixed linear model in PLINK software. After quality control, 28749 markers on 142 cows (99 cases and 43 controls) were remained for the further analysis. Associations analysis showed that 16 markers located in chromosomes 30 and 6, were associated with  Johne's disease. Positional candidate genes for Johne's disease were identified. The most important identified genes were LMX1A, THSD7A, ELMOD2, ATP6AP2, RNF150, SLIT3, SDE2, PARP1, PBX1, TFB2M, SMYD3 and PYCR2. Gene ontology analysis showed that most of the identified genes are involved in the nervous system, cytoskeleton system, regulation of cytokines, Golgi apparatus, catalytic activity, calcium ion transport, and resistance to diseases. Whole genome-wide association study (GWAS) and ontology analysis (GO) can help to identify candidate genes and regions related to sensitivity to MAP in dairy cows, which can play an important role in the treatment and prevention of Johne's disease.