Genome-Wide Association Study in Mexican Holstein Cattle Reveals Novel Quantitative Trait Loci Regions and Confirms Mapped Loci for Resistance to Bovine Tuberculosis

SIMPLE SUMMARY: Bovine tuberculosis is an infectious disease of cattle caused by Mycobacterium bovis characterized by the formation of tubercles in any organ or tissue. Bovine tuberculosis represents a significant veterinary and public health problem in many parts of the world. It is zoonotic, transmitted to humans through consumption of infected milk and other cattle products. Although many factors influence infection and progression of the disease, there must be an important host genetic component that explains why some animals get sick and others remain healty. We present evidence of genetic variants associated with resistance to tuberculosis in Mexican Holstein dairy cattle using a case-control approach with a selective DNA pooling. Here, we identified novel quantitative trait loci regions harboring genes involved in Mycobacterium spp. immune response. This is a first screening about resistance to tuberculosis infection on Mexican Holstein cattle based on a dense single nucleotide polymorphism chip. The identified genes belong to both, the already known, and the undisclosed quantitative trait loci regions. ABSTRACT: Bovine tuberculosis (bTB) is a disease of cattle that represents a risk to public health and causes severe economic losses to the livestock industry. Recently, genetic studies, like genome-wide association studies (GWAS) have greatly improved the investigation of complex diseases identifying thousands of disease-associated genomic variants. Here, we present evidence of genetic variants associated with resistance to TB in Mexican dairy cattle using a case-control approach with a selective DNA pooling experimental design. A total of 154 QTLRs (quantitative trait loci regions) at 10% PFP (proportion of false positives), 42 at 5% PFP and 5 at 1% PFP have been identified, which harbored 172 annotated genes. On BTA13, five new QTLRs were identified in the MACROD2 and KIF16B genes, supporting their involvement in resistance to bTB. Six QTLRs harbor seven annotated genes that have been previously reported as involved in immune response against Mycobacterium spp: BTA (Bos taurus autosome) 1 (CD80), BTA3 (CTSS), BTA 3 (FCGR1A), BTA 23 (HFE), BTA 25 (IL21R), and BTA 29 (ANO9 and SIGIRR). We identified novel QTLRs harboring genes involved in Mycobacterium spp. immune response. This is a first screening for resistance to TB infection on Mexican dairy cattle based on a dense SNP (Single Nucleotide Polymorphism) chip.