title: A hereditary disposition for bovine peripheral nerve sheath tumors in Danish Holstein cattle.
abstract: BACKGROUND
  Peripheral nerve sheath tumors (PNSTs) are frequently found in Danish cattle at slaughter. Bovine PNSTs share several gross and histopathological characteristics with the PNSTs in humans with heritable neurofibromatosis syndromes. The aim of the present study was to investigate a possible hereditary disposition to PNSTs in dairy cattle by statistical analysis performed on data from 567 cattle with PNSTs. Furthermore, a preliminary genome-wide association study (GWAS) was performed on DNA isolated from 28 affected and 28 non-affected Holstein cows to identify loci in the bovine genome involved in the development of PNSTs.
  
  
  RESULTS
  PNSTs were significantly more common in the Danish Holstein breed than in other breeds with 0.49% of Danish Holsteins slaughtered during an eight-year-period having PNSTs. PNSTs also occurred significantly more frequently in the offspring of some specific Holstein sires. Examination of three generation pedigrees showed that these sires were genetically related through a widely used US Holstein sire. The PNSTs included in GWAS were histologically classified as neurofibroma-schwannoma (43%), schwannoma (36%) and neurofibroma (21%) and derived from Holstein cows with multiple PNSTs. A single SNP on chromosome 27 reached genome-wide significance.
  
  
  CONCLUSIONS
  Gross and histological characteristics of bovine PNSTs are comparable to PNSTs in humans (schwannomatosis). Danish Holsteins are genetically disposed to develop PNSTs but the examined materials are insufficient to allow determination of the mode of inheritance.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 3, 1870, Frederiksberg C, Denmark. abg@minipigs.dk.|Present address: Ellegaard Göttingen Minipigs A/S, Sorø Landevej 302, 4261, Dalmose, Denmark. abg@minipigs.dk.
authors.forename: Anette B
authors.initials: AB
authors.lastname: Grossi
authors.affiliation: Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlægevej 68, 1870, Frederiksberg C, Denmark. jager@sund.ku.dk.
authors.forename: Jørgen S
authors.initials: JS
authors.lastname: Agerholm
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark. kc@sund.ku.dk.
authors.forename: Knud
authors.initials: K
authors.lastname: Christensen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 3, 1870, Frederiksberg C, Denmark. helj@sund.ku.dk.
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Jensen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 3, 1870, Frederiksberg C, Denmark. ple@sund.ku.dk.
authors.forename: Páll S
authors.initials: PS
authors.lastname: Leifsson
authors.affiliation: Department of Molecular Biology and Genetics, Faculty of Science and Technology, University of Aarhus, Blichers Allé 20, 8830, Tjele, Denmark. christian.bendixen@mbg.au.dk.
authors.forename: Christian
authors.initials: C
authors.lastname: Bendixen
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark. pkm@sund.ku.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Karlskov-Mortensen
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark. mf@sund.ku.dk.
authors.forename: Merete
authors.initials: M
authors.lastname: Fredholm
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000453:epidemiology* / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D005260:Female; D055106:Genome-Wide Association Study / Q000662:veterinary*; D015994:Incidence; D008297:Male; D018317:Nerve Sheath Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000662:veterinary*; D015995:Prevalence