An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. It powerfully increases the risk associated with smoking and hypertension. It is time to undertake randomized controlled trials of the effect of vitamins that reduce plasma homocysteine levels on vascular disease risk.

Selected demographic features and trends in bovine tuberculosis (BTB) from 1995 to 2010 are described for the countries of the UK and the Republic of Ireland, using standardised definitions and measures. All countries experienced a reduction in the number of cattle and herds and in the proportion of dairy herds, while average herd size increased. In general, the trends indicate a stable situation of very low BTB prevalence in Scotland and, over most of the period, a rising prevalence in England and Wales. The prevalence in the Republic of Ireland declined while Northern Ireland experienced both a rise and fall. Differences in demography, BTB programme structure and test results were noted, particularly between the island of Ireland and Great Britain. Further investigation of these differences may provide valuable insights into risk factors for BTB and optimisation of existing BTB programmes.

Information is lacking on genetic parameters for tuberculosis (TB) susceptibility in dairy cattle. Mycobacterium bovis is the principal agent of tuberculosis in cattle. The objective of this study was to quantify the genetic variation present among Irish Holstein-Friesian dairy herds in their susceptibility to M. bovis infection. A total of 15,182 cow and 8,104 heifer single intradermal comparative tuberculin test (SICTT, a test for M. bovis exposure and presumed infection) records from November 1, 2002, to October 31, 2005, were available for inclusion in the analysis. Data on observed carcass TB lesions from abattoirs were also available for inclusion in the analysis. The only animals retained were those present in a herd during episodes in which at least 2 animals showed evidence of infection; this ensured a high likelihood of exposure to M. bovis. Linear animal models, and sire and animal threshold models were used to estimate the variance components for susceptibility to M. bovis-purified protein derivative (PPD) responsiveness and confirmed M. bovis infection. The heritability estimates from the threshold sire models were biased upward because the relatedness between dam-daughter pairs was ignored. The threshold animal model produced heritability estimates of 0.14 in cows and 0.12 in heifers for susceptibility to M. bovis-PPD responsiveness, and 0.18 in cows for confirmed M. bovis infection susceptibility. Therefore, exploitable genetic variation exists among Irish dairy cows for susceptibility to M. bovis infection. Sire rankings from the linear and threshold animal models were similar, indicating that either model could be used for the analysis of susceptibility to M. bovis-PPD responsiveness. A favorable genetic correlation close to unity was observed between susceptibility to confirmed M. bovis infection and M. bovis-PPD responsiveness, indicating that direct selection for resistance to M. bovis-PPD responsiveness will indirectly reduce susceptibility to confirmed M. bovis infection. Data from the national TB eradication program could be used routinely to estimate breeding values for susceptibility to M. bovis infection.

BackgroundBovine 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.MethodsTwo 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.ResultsA 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.ConclusionsA 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-016-0197-x) contains supplementary material, which is available to authorized users.

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