Fine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cows

Abstract Background Susceptibility to Mycobacterium bovis infection in cattle is governed in part by host genetics. However, cattle diagnosed as infected with M. bovis display varying signs of pathology. The variation in host response to infection could represent a continuum since time of exposure or distinct outcomes due to differing pathogen handling. The relationships between host genetics and variation in host response and pathological sequelae following M. bovis infection were explored by genotyping 1966 Holstein-Friesian dairy cows at 538,231 SNPs with three distinct phenotypes. These were: single intradermal cervical comparative tuberculin (SICCT) test positives with visible lesions (VLs), SICCT-positives with undetected visible lesions (NVLs) and matched controls SICCT-negative on multiple occasions. Results Regional heritability mapping identified three loci associated with the NVL phenotype on chromosomes 17, 22 and 23, distinct to the region on chromosome 13 associated with the VL phenotype. The region on chromosome 23 was at genome-wide significance and candidate genes overlapping the mapped window included members of the bovine leukocyte antigen class IIb region, a complex known for its role in immunity and disease resistance. Chromosome heritability analysis attributed variance to six and thirteen chromosomes for the VL and NVL phenotypes, respectively, and four of these chromosomes were found to explain a proportion of the phenotypic variation for both the VL and NVL phenotype. By grouping the M. bovis outcomes (VLs and NVLs) variance was attributed to nine chromosomes. When contrasting the two M. bovis infection outcomes (VLs vs NVLs) nine chromosomes were found to harbour heritable variation. Regardless of the case phenotype under investigation, chromosome heritability did not exceed 8% indicating that the genetic control of bTB resistance consists of variants of small to moderate effect situated across many chromosomes of the bovine genome. Conclusions These findings suggest the host genetics of M. bovis infection outcomes is governed by distinct and overlapping genetic variants. Thus, variation in the pathology of M. bovis infected cattle may be partly genetically determined and indicative of different host responses or pathogen handling. There may be at least three distinct outcomes following M. bovis exposure in dairy cattle: resistance to infection, infection resulting in pathology or no detectable pathology

Solar angle of the distal phalanx is associated with scintigraphic evidence of subchondral bone injury in the palmar/plantar aspect of the third metacarpal/tarsal condyles in Thoroughbred racehorses

BACKGROUND: Subchondral bone injury at the palmar/plantar aspect of the condyles of the third metacarpal/metatarsal bone (MC/MT3) commonly causes lameness and poor performance in racehorses. Injury occurs due to repetitive loading, the magnitude of which may be influenced by the position of the distal phalanx relative to the ground surface, i.e. the solar angle. The association of solar angle and injury at the palmar/plantar condyles of distal MC/MT3 therefore warrants investigation. OBJECTIVES: Investigate the relationship between solar angle and radiopharmaceutical uptake at the palmar/plantar aspect of distal MC/MT3 on scintigraphic images of racehorses. STUDY DESIGN: Retrospective case-controlled study. METHODS: Scintigraphic images of Thoroughbred racehorses presented for poor performance or lameness were graded for intensity of radiopharmaceutical uptake in the palmar/plantar aspect of distal MC/MT3. Solar angle was graded (positive, neutral or negative), referring to the angle of the solar plane of the distal phalanx relative to the ground surface. Repeatability of solar angle (n = 1226 limbs) and agreement with objective radiographic evaluation (n = 52 limbs) were evaluated. Prescintigraphy performance data were collected from race records. Associations between solar angle, performance and radiopharmaceutical uptake were investigated using multivariable logistic regression. RESULTS: Repeatability of scintigraphic solar angle grading (κ = 0.89, 95% CI 0.87-0.91) and agreement of scintigraphic and radiographic solar angle (κ = 0.88, 95% CI 0.75-0.97) were excellent. Horses that performed best prior to presentation were more likely to have both greater radiopharmaceutical uptake and a neutral/negative solar angle. When controlling for prior performance, horses with neutral/negative forelimb solar angle were twice as likely to have moderate/marked radiopharmaceutical uptake than horses with positive solar angle (P<0.02). Horses with negative hindlimb solar angle were six times more likely to have moderate/marked radiopharmaceutical uptake than horses with positive/neutral solar angle (P<0.001). MAIN LIMITATIONS: Population bias due to preselected hospital population. CONCLUSIONS: Both solar angle and race performance are independently associated with increased bone activity in the palmar/plantar aspect of the third metacarpal/tarsal condyles. The Summary is available in Portuguese - see Supporting Information