Genome-Wide Association Analysis Identifies Suggestive Loci and Implicates SLC11A1 as a Positional Candidate Gene for Bovine Tuberculosis Resistance in Nili-Ravi Buffalo (Bubalus bubalis)

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains an important constraint to water buffalo (Bubalus bubalis) productivity and a zoonotic risk within Pakistan's dairy sector. In this study, we performed a genome-wide association scan for single intradermal comparative cervical tuberculin (SICCT) reactor status in Nili-Ravi buffalo using the Axiom Buffalo array (90K), followed by a focused evaluation of the SLC11A1 (NRAMP1) candidate region. After quality control, 45,183 SNPs were retained for analysis, and a confirmed subset of 85 animals was used for the targeted study (50 SICCT-negative and 35 SICCT-positive). No marker achieved genome-wide significance in the full scan. However, within the SLC11A1 interval, the strongest nominal association was observed for AX-85139659 (odds ratio = 13.2, Fisher's P = 0.0039), followed by AX-85109412 (odds ratio = 0.09, P = 0.0092) and AX-85128873 (odds ratio = 0.14, P = 0.0457). The first two SNPs were located within a shared 27 kb haplotype block, with complete linkage disequilibrium (D′ = 1.00, r² = 0.76), suggesting that they are likely inherited together rather than representing independent signals. The identified SNPs in the SLC11A1 region provide preliminary evidence for genetic variation associated with bTB resistance in Nili-Ravi buffalo and warrant validation in larger populations.