A genome-wide association study for genetic susceptibility to Mycobacterium bovis infection in dairy cattle identifies a susceptibility QTL on chromosome 23.

BACKGROUND: Bovine tuberculosis (bTB) infection in cattle is a significant economic concern in many countries, with annual costs to the UK and Irish governments of approximately €190 million and €63 million, respectively, for bTB control. The existence of host additive and non-additive genetic components to bTB susceptibility has been established. METHODS: Two approaches i.e. single-SNP (single nucleotide polymorphism) regression and a Bayesian method were applied to genome-wide association studies (GWAS) using high-density SNP genotypes (n = 597,144 SNPs) from 841 dairy artificial insemination (AI) sires. Deregressed estimated breeding values for bTB susceptibility were used as the quantitative dependent variable. Network analysis was performed using the quantitative trait loci (QTL) that were identified as significant in the single-SNP regression and Bayesian analyses separately. In addition, an identity-by-descent analysis was performed on a subset of the most prolific sires in the dataset that showed contrasting prevalences of bTB infection in daughters. RESULTS: A significant QTL region was identified on BTA23 (P value >1 × 10(-5), Bayes factor >10) across all analyses. Sires with the minor allele (minor allele frequency = 0.136) for this QTL on BTA23 had estimated breeding values that conferred a greater susceptibility to bTB infection than those that were homozygous for the major allele. Imputation of the regions that flank this QTL on BTA23 to full sequence indicated that the most significant associations were located within introns of the FKBP5 gene. CONCLUSIONS: A genomic region on BTA23 that is strongly associated with host susceptibility to bTB infection was identified. This region contained FKBP5, a gene involved in the TNFα/NFκ-B signalling pathway, which is a major biological pathway associated with immune response. Although there is no study that validates this region in the literature, our approach represents one of the most powerful studies for the analysis of bTB susceptibility to date.

Variance components for susceptibility to Mycobacterium bovis infection in dairy and beef cattle.

BACKGROUND: Infection of livestock with bovine tuberculosis (bTB; Mycobacterium bovis) is of major economical concern in many countries; approximately 15 000 to 20 000 cattle are infected per year in Ireland. The objective of this study was to quantify the genetic variation for bTB susceptibility in Irish dairy and beef cattle. METHODS: A total of 105 914 cow, 56 904 heifer and 21 872 steer single intra-dermal comparative tuberculin test records (i.e., binary trait) collected from the years 2001 to 2010 from dairy and beef herds were included in the analysis. Only animal level data pertaining to periods of herd bTB infection were retained. Variance components for bTB were estimated using animal linear and threshold mixed models and co-variances were estimated using sire linear mixed models. RESULTS: Using a linear model, the heritability for susceptibility to bTB in the entire dataset was 0.11 and ranged from 0.08 (heifers in dairy herds) to 0.19 (heifers in beef herds) among the sub-populations investigated. Differences in susceptibility to bTB between breeds were clearly evident. Estimates of genetic correlations for bTB susceptibility between animal types (i.e., cows, heifers, steers) were all positive (0.10 to 0.64), yet different from one. Furthermore, genetic correlations for bTB susceptibility between environments that differed in herd prevalence of bTB ranged from 0.06 to 0.86 and were all different from one. CONCLUSIONS: Genetic trends for bTB susceptibility observed in this study suggest a slight increase in genetic susceptibility to bTB in recent years. Since bTB is of economic importance and because all animals are routinely tested at least once annually in Ireland and some other countries, the presence of genetic variation for bTB susceptibility suggests that bTB susceptibility should be included in a national breeding program to halt possible deterioration in genetic susceptibility to bTB infection.

A Population Genomics Analysis of the Native Irish Galway Sheep Breed.

The Galway sheep population is the only native Irish sheep breed and this livestock genetic resource is currently categorised as 'at-risk'. In the present study, comparative population genomics analyses of Galway sheep and other sheep populations of European origin were used to investigate the microevolution and recent genetic history of the breed. These analyses support the hypothesis that British Leicester sheep were used in the formation of the Galway. When compared to conventional and endangered breeds, the Galway breed was intermediate in effective population size, genomic inbreeding and runs of homozygosity. This indicates that, although the Galway breed is declining, it is still relatively genetically diverse and that conservation and management plans informed by genomic information may aid its recovery. The Galway breed also exhibited distinct genomic signatures of artificial or natural selection when compared to other breeds, which highlighted candidate genes that may be involved in production and health traits.

Genomic Characterisation of the Indigenous Irish Kerry Cattle Breed.

Kerry cattle are an endangered landrace heritage breed of cultural importance to Ireland. In the present study we have used genome-wide SNP array data to evaluate genomic diversity within the Kerry population and between Kerry cattle and other European breeds. Patterns of genetic differentiation and gene flow among breeds using phylogenetic trees with ancestry graphs highlighted historical gene flow from the British Shorthorn breed into the ancestral population of modern Kerry cattle. Principal component analysis (PCA) and genetic clustering emphasised the genetic distinctiveness of Kerry cattle relative to comparator British and European cattle breeds. Modelling of genetic effective population size (Ne) revealed a demographic trend of diminishing Ne over time and that recent estimated Ne values for the Kerry breed may be less than the threshold for sustainable genetic conservation. In addition, analysis of genome-wide autozygosity (FROH) showed that genomic inbreeding has increased significantly during the 20 years between 1992 and 2012. Finally, signatures of selection revealed genomic regions subject to natural and artificial selection as Kerry cattle adapted to the climate, physical geography and agro-ecology of southwest Ireland.