title: Evidence for a genetic basis of urogenital carcinoma in the wild California sea lion.
abstract: Although neoplasia is a major cause of mortality in humans and domestic animals, it has rarely been described in wildlife species. One of the few examples is a highly prevalent urogenital carcinoma in California sea lions (CSLs). Although the aetiology of this carcinoma is clearly multifactorial, inbreeding depression, as estimated using levels of microsatellite multilocus heterozygosity, is identified as predictive for this neoplasia. On further analysis, this relationship appears to be largely driven by one marker, suggesting that a single locus might be associated with the occurrence of this disease in CSLs. In a case-control study, carcinoma was significantly associated with homozygosity at the Pv11 microsatellite locus. Pv11 was mapped to intron 9 of the heparanase 2 gene (HPSE2) locus, a very large gene encoding heparanase 2, which in humans is associated with multiple carcinomas. Correspondingly, immunohistochemical labelling in tissues was present in carcinoma cases within a single homozygous Pv11 genotype. To our knowledge, this is the first report of an individual locus being associated with cancer in any wildlife species. This adds emphasis to the study of HPSE2 in other species, including humans and will guide future studies on this sentinel species that shares much of its diet and environment with humans.
authors.affiliation: Sea Mammal Research Unit, Scottish Oceans Institute, University of St Andrews, Fife, UK.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Browning
authors.affiliation: Unit for Basic and Applied Microbiology, Autonomous University of Querétaro, Querétaro, Mexico.
authors.forename: Karina
authors.initials: K
authors.lastname: Acevedo-Whitehouse
authors.affiliation: The Marine Mammal Center, Fort Cronkhite, Sausalito, CA, USA.
authors.forename: Frances M D
authors.initials: FM
authors.lastname: Gulland
authors.affiliation: Sea Mammal Research Unit, Scottish Oceans Institute, University of St Andrews, Fife, UK.
authors.forename: Ailsa J
authors.initials: AJ
authors.lastname: Hall
authors.affiliation: The Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, UK.
authors.forename: Jeanie
authors.initials: J
authors.lastname: Finlayson
authors.affiliation: The Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, UK.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Dagleish
authors.affiliation: Pirbright Laboratory, The Pirbright Institute, Surrey, UK.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Billington
authors.affiliation: Zoological Pathology Program, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Maywood, IL, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Colegrove
authors.affiliation: Pirbright Laboratory, The Pirbright Institute, Surrey, UK john.hammond@pirbright.ac.uk.
authors.forename: John A
authors.initials: JA
authors.lastname: Hammond
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000662:veterinary*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005966:Glucuronidase / Q000235:genetics; D007178:Inbreeding; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D016017:Odds Ratio; D046070:Sea Lions / Q000235:genetics*; D014565:Urogenital Neoplasms / Q000235:genetics / Q000662:veterinary*
chemical_list: D005966:Glucuronidase
keywords: cancer; heparanase 2 gene; odds ratio; wildlife