Genomic regions underlying susceptibility to bovine tuberculosis in Holstein-Friesian cattle

Abstract

BackgroundThe significant social and economic loss as a result of bovine tuberculosis (bTB) presents a continuous challenge to cattle industries in the UK and worldwide. However, host genetic variation in cattle susceptibility to bTB provides an opportunity to select for resistant animals and further understand the genetic mechanisms underlying disease dynamics.MethodsThe present study identified genomic regions associated with susceptibility to bTB using genome-wide association (GWA), regional heritability mapping (RHM) and chromosome association approaches. Phenotypes comprised de-regressed estimated breeding values of 804 Holstein-Friesian sires and pertained to three bTB indicator traits: i) positive reactors to the skin test with positive post-mortem examination results (phenotype 1); ii) positive reactors to the skin test regardless of post-mortem examination results (phenotype 2) and iii) as in (ii) plus non-reactors and inconclusive reactors to the skin tests with positive post-mortem examination results (phenotype 3). Genotypes based on the 50 K SNP DNA array were available and a total of 34,874 SNPs remained per animal after quality control.ResultsThe estimated polygenic heritability for susceptibility to bTB was 0.26, 0.37 and 0.34 for phenotypes 1, 2 and 3, respectively. GWA analysis identified a putative SNP on Bos taurus autosomes (BTA) 2 associated with phenotype 1, and another on BTA 23 associated with phenotype 2. Genomic regions encompassing these SNPs were found to harbour potentially relevant annotated genes. RHM confirmed the effect of these genomic regions and identified new regions on BTA 18 for phenotype 1 and BTA 3 for phenotypes 2 and 3. Heritabilities of the genomic regions ranged between 0.05 and 0.08 across the three phenotypes. Chromosome association analysis indicated a major role of BTA 23 on susceptibility to bTB.ConclusionGenomic regions and candidate genes identified in the present study provide an opportunity to further understand pathways critical to cattle susceptibility to bTB and enhance genetic improvement programmes aiming at controlling and eradicating the disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-017-0493-7) contains supplementary material, which is available to authorized users.

Summaries invited

“…SNP markers associated with bTB resistance will improve the accuracy of predictors (Tsairidou et al, 2014) and identify genomic regions for bTB resistance in cattle. We have identified a number of loci and candidate genes in three genome wide association (GWA) studies for bTB resistance Raphaka et al, 2017;Wilkinson et al, 2017). We have now whole genome sequenced 88 HF sires with known estimated breeding values (EBV) for bTB resistance in order to provide novel information that could enhance accuracy of genomic predictors as well as identifying novel SNPs closer to the causal loci for bTB resistance in cattle.…”

A putative genomic map for resistance ofBos indicuscattle in Cameroon to bovine tuberculosis

“…This region did not overlap with any other regions identified by studies of bTB resistance in cattle eg. (Bermingham et al, 2014; Finlay et al, 2012; Richardson et al, 2016; le Roex et al, 2013; Tsairidou et al, 2018; Amos et al, 2013; Driscoll et al, 2011; Raphaka et al, 2017). However, one of the genes within ±500Kbp of this region was tumor necrosis factor (TNF).…”

“…A Bonferroni correction was applied to the genome-wide significance threshold, calculated as p = − log 10 (0.05/ n ) = 7.00 (where n is the number of SNPs, n = 500815). Regions surrounding 100000bp of SNPs which had been identified as being associated with bTB resistance in cattle in the literature (Bermingham et al, 2014; Finlay et al, 2012; Richardson et al, 2016; le Roex et al, 2013; Tsairidou et al, 2018; Amos et al, 2013; Driscoll et al, 2011; Raphaka et al, 2017) were also evaluated with a lower significance threshold of p = − log 10 (0.05/45780) = 5.96.…”

Resistencia natural contra la tuberculosis en ganado. Revisión

“…Un estudio reciente que incluye el análisis de diferentes fenotipos (animales reactores a tuberculina, lesiones visibles y aislamiento de M. bovis por cultivo) en la susceptibilidad a TBb, identificó 2 SNP, en los cromosomas 2 y 23, asociados significativamente con diferentes rasgos de susceptibilidad, los cuales proporcionan posibles marcadores para la selección de individuos susceptibles, diferenciándolos de aquéllos con el potencial de resistencia a la enfermedad (27) .…”