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



The 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.



The 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.



Genomic 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.
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland, UK. kethusegile.raphaka@roslin.ed.ac.uk.
Kethusegile
K
Raphaka
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland, UK.
Oswald
O
Matika
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland, UK.
Enrique
E
Sánchez-Molano
Scotland's Rural College, The Roslin Institute Building, Easter Bush, Midlothian, EH25 9RG, Edinburgh, UK.
Raphael
R
Mrode
Scotland's Rural College, The Roslin Institute Building, Easter Bush, Midlothian, EH25 9RG, Edinburgh, UK.
Mike Peter
MP
Coffey
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland, UK.
Valentina
V
Riggio
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland, UK.
Elizabeth Janet
EJ
Glass
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland, UK.
John Arthur
JA
Woolliams
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland, UK.
Stephen Christopher
SC
Bishop
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland, UK.|Scotland's Rural College, The Roslin Institute Building, Easter Bush, Midlothian, EH25 9RG, Edinburgh, UK.
Georgios
G
Banos
D000818:Animals; D002417:Cattle; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D023281:Genomics; D014380:Tuberculosis, Bovine / Q000235:genetics*
Bovine tuberculosis; Chromosome association; Genome-wide association; Regional heritability mapping; Susceptibility