title: An across-breed genome wide association analysis of susceptibility to paratuberculosis in dairy cattle.
abstract: Paratuberculosis is a chronic disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). It occurs worldwide and causes a significant loss in the animal production industry. There is no cure for MAP infection and vaccination is problematic. Identification of genetics of susceptibility could be a useful adjunct for programs that focus on management, testing and culling of diseased animals. A case-control, genome-wide association study (GWAS) was conducted using Holstein and Jersey cattle in a combined analysis in order to identify markers and chromosomal regions associated with susceptibility to MAP infection across-breed. A mixed-model method (GRAMMAR-GC) implemented in the GenABEL R package and a Bayes C analysis implemented in GenSel software were used as alternative approaches to conduct GWAS analysis focused on single SNPs and chromosomal segments, respectively. After conducting quality control, 22 406 SNPs from 2157 individuals were available for the GRAMMAR-GC (Bayes C) analysis and 45 640 SNPs from 2199 individuals were available for the Bayes C analysis. One SNP located on BTA27 (8·6 Mb) was identified as moderately associated (P < 5 × 10-5, FDR = 0·44) in the GRAMMAR-GC analysis of the combined breed data. Nine 1 Mb windows located on BTA 2, 3 (3 windows), 6, 8, 25, 27 and 29 each explained ≥1% of the total proportion of genetic variance in the Bayes C analysis. In an analysis ignoring differences in linkage phase, two moderately significantly associated SNPs were identified; ARS-BFGL-NGS-19381 on BTA23 (32 Mb) and Hapmap40994-BTA-46361 on BTA19 (61 Mb). New common genomic regions and candidate genes have been identified from the across-breed analysis that might be involved in the immune response and susceptibility to MAP infection.
authors.affiliation: Department of Animal Sciences,College of Agricultural and Life Sciences,University of Wisconsin-Madison,Madison,WI 53706,USA.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Sallam
authors.affiliation: Department of Animal Sciences,College of Agricultural and Life Sciences,University of Wisconsin-Madison,Madison,WI 53706,USA.
authors.forename: Yalda
authors.initials: Y
authors.lastname: Zare
authors.affiliation: Department of Animal Sciences,College of Agricultural and Life Sciences,University of Wisconsin-Madison,Madison,WI 53706,USA.
authors.forename: Fazli
authors.initials: F
authors.lastname: Alpay
authors.affiliation: Department of Dairy Science,College of Agricultural and Life Sciences,University of Wisconsin-Madison,Madison,WI 53706,USA.
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,WI 53706,USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Collins
authors.affiliation: Animal and Poultry Production Division,Desert Research Center,Al-Mataria 11753,Cairo,Egypt.
authors.forename: Samir
authors.initials: S
authors.lastname: Alsheikh
authors.affiliation: Animal and Fish Production Department,Faculty of Agriculture,University of Alexandria,El-Shatby,Alexandria,Egypt.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Sharaby
authors.affiliation: Department of Animal Sciences,College of Agricultural and Life Sciences,University of Wisconsin-Madison,Madison,WI 53706,USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Kirkpatrick
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D001947:Breeding; D002417:Cattle / Q000235:genetics; D002418:Cattle Diseases / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods / Q000662:veterinary*; D005838:Genotype; D010283:Paratuberculosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013045:Species Specificity
keywords: Gene; Johne's disease; cow