Genome-wide association study identifies novel loci associated with resistance to
bovine tuberculosis |
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Authors: | M L Bermingham S C Bishop J A Woolliams R Pong-Wong A R Allen S H McBride J J Ryder D M Wright R A Skuce S WJ McDowell E J Glass |
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Institution: | 1.The Roslin Institute and Royal (Dick) School
of Veterinary Studies, University of Edinburgh, Edinburgh, UK;2.Agri-Food and Biosciences Institute
Stormont, Belfast, UK;3.Queen''s University Belfast, School of
Biological Sciences, Medical Biology Centre, Belfast, UK |
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Abstract: | 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. |
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Keywords: | genome-wide association study bovine tuberculosis novel resistance loci |
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