Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis.
Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of livestock that is of major economic importance worldwide, as well as being a zoonotic risk. There is significant heritability for host resistance to bovine TB (bTB) in dairy cattle. To identify resistance loci for bTB, we undertook a genome-wide association study in female Holstein-Friesian cattle with 592 cases and 559 age-matched controls from case herds. Cases and controls were categorised into distinct phenotypes: skin test and lesion positive vs skin test negative on multiple occasions, respectively. These animals were genotyped with the Illumina BovineHD 700K BeadChip. Genome-wide rapid association using linear and logistic mixed models and regression (GRAMMAR), regional heritability mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that attained chromosome-wise significance, protein tyrosine phosphatase receptor T (PTPRT; P=4.8 × 10(-7)) and myosin IIIB (MYO3B; P=5.4 × 10(-6)). We estimated that 21% of the phenotypic variance in TB resistance could be explained by all of the informative single-nucleotide polymorphisms, of which the region encompassing the PTPRT gene accounted for 6.2% of the variance and a further 3.6% was associated with a putative copy number variant in MYO3B. The results from this study add to our understanding of variation in host control of infection and suggest that genetic marker-based selection for resistance to bTB has the potential to make a significant contribution to bTB control.
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
M L
ML
Bermingham
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
S C
SC
Bishop
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
J A
JA
Woolliams
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
R
R
Pong-Wong
Agri-Food and Biosciences Institute Stormont, Belfast, UK.
A R
AR
Allen
Agri-Food and Biosciences Institute Stormont, Belfast, UK.
S H
SH
McBride
Queen's University Belfast, School of Biological Sciences, Medical Biology Centre, Belfast, UK.
J J
JJ
Ryder
Queen's University Belfast, School of Biological Sciences, Medical Biology Centre, Belfast, UK.
D M
DM
Wright
1] Agri-Food and Biosciences Institute Stormont, Belfast, UK [2] Queen's University Belfast, School of Biological Sciences, Medical Biology Centre, Belfast, UK.
R A
RA
Skuce
Agri-Food and Biosciences Institute Stormont, Belfast, UK.
S Wj
SW
McDowell
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
E J
EJ
Glass
D000818:Animals; D002417:Cattle; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics; D060467:Disease Resistance / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000662:veterinary*; D005838:Genotype; D006239:Haplotypes; D054884:Host-Pathogen Interactions / Q000235:genetics; D016014:Linear Models; D015810:Linkage Disequilibrium; D016015:Logistic Models; D009163:Mycobacterium bovis / Q000502:physiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014380:Tuberculosis, Bovine / Q000235:genetics* / Q000382:microbiology