Whole-Genome association analysis of susceptibility to paratuberculosis in Holstein cattle.

The objective of this study was to identify genetic markers and genomic regions associated with susceptibility to Mycobacterium avium ssp. paratuberculosis (MAP) infection in Holstein cattle. Associated single nucleotide polymorphisms (SNPs) were identified by genotyping 521 MAP-infected Holstein cows and comparing SNP allele frequencies of these infected cows with allele frequencies estimated from specific reference populations. Reference population allele frequency estimates used Holstein sire genotype data and were weighted estimates based on sire usage within the population in question. The 521 infected cows were 233 and 288 cows from two resource populations of approximately 5000 cows each, collected independently. Population 1 was comprised primarily of daughters of twelve Holstein artificial insemination sires used heavily within the US dairy cattle population. Samples were obtained from 300 co-operating commercial dairy herds throughout the US and were tested by both MAP faecal culture and blood-enzyme-linked immunosorbent assay (ELISA). Population 2 consisted of dairy cattle from six co-operating dairy herds in Wisconsin, with all animals in the herds tested by blood enzyme-linked immunosorbent assay (ELISA) for MAP infection. Genotyping was performed with the Illumina Bovine SNP50 Bead Chip, providing genotypes for 35,772 informative SNPs. Data from the two resource populations were analysed both in separate and combined analyses. The most significant autosomal markers from the individual and combined analyses (n=197, nominal P<0.001) were used in a stepwise logistic regression analysis to identify a set of 51 SNPs that could be used as a predictor of genetics for Holstein cattle susceptibility to MAP infection.