title: Genome-wide association study of susceptibility to infection by Mycobacterium avium subspecies paratuberculosis in Holstein cattle.
abstract: Paratuberculosis, or Johne's disease, is a chronic, granulomatous, gastrointestinal tract disease of cattle and other ruminants caused by the bacterium Mycobacterium avium, subspecies paratuberculosis (MAP). Control of Johne's disease is based on programs of testing and culling animals positive for infection with MAP while concurrently modifying management to reduce the likelihood of infection. The current study is motivated by the hypothesis that genetic variation in host susceptibility to MAP infection can be dissected and quantifiable associations with genetic markers identified. For this purpose, a case-control, genome-wide association study was conducted using US Holstein cattle phenotyped for MAP infection using a serum ELISA and/or fecal culture test. Cases included cows positive for either serum ELISA, fecal culture or both. Controls consisted of animals negative for the serum ELISA test or both serum ELISA and fecal culture when both were available. Controls were matched by herd and proximal birth date with cases. A total of 856 cows (451 cases and 405 controls) were used in initial discovery analyses, and an additional 263 cows (159 cases and 104 controls) from the same herds were used as a validation data set. Data were analyzed in a single marker analysis controlling for relatedness of individuals (GRAMMAR-GC) and also in a Bayesian analysis in which multiple marker effects were estimated simultaneously (GenSel). For the latter, effects of non-overlapping 1 Mb marker windows across the genome were estimated. Results from the two discovery analyses were generally concordant; however, discovery results were generally not well supported in analysis of the validation data set. A combined analysis of discovery and validation data sets provided strongest support for SNPs and 1 Mb windows on chromosomes 1, 2, 6, 7, 17 and 29.
authors.affiliation: Department of Animal Science, Faculty of Veterinary Medicine, Uludag University, Bursa, 16059, Turkey.
authors.forename: Fazli
authors.initials: F
authors.lastname: Alpay
authors.affiliation: Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin, 53706, United States of America.
authors.forename: Yalda
authors.initials: Y
authors.lastname: Zare
authors.affiliation: Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin, 53706, United States of America; Department of Animal Science, Faculty of Agriculture, Universiti Putra, UPM Serdang, Selangor, Malaysia.
authors.forename: Mamat H
authors.initials: MH
authors.lastname: Kamalludin
authors.affiliation: College of Animal Science, Xinjiang Agricultural University, Urumqi, Xinjiang, China.
authors.forename: Xixia
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin, 53706, United States of America.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Dairy Science, University of Wisconsin-Madison, Madison, Wisconsin, 53706, United States of America.
authors.forename: George E
authors.initials: GE
authors.lastname: Shook
authors.affiliation: Department of Pathobiological Science, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, 53706, United States of America.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Collins
authors.affiliation: Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin, 53706, United States of America; Department of Dairy Science, University of Wisconsin-Madison, Madison, Wisconsin, 53706, United States of America.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Kirkpatrick
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D002417:Cattle; D005243:Feces / Q000382:microbiology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016927:Mycobacterium avium subsp. paratuberculosis / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014376:Tuberculosis / Q000235:genetics* / Q000382:microbiology / Q000662:veterinary