@article{843f7d03682c4d55be9924dfff24db3b,
title = "A FAS-ligand variant associated with autoimmune lymphoproliferative syndrome in cats",
abstract = "British shorthair (BSH) kittens in multiple litters died as a result of a severe non-neoplastic lymphoproliferative disease that showed many similarities with human autoimmune lymphoproliferative syndrome (ALPS). Human ALPS is caused by inherited defects in FAS-mediated lymphocyte apoptosis and the possibility of similar defects was investigated in BSH cats. The whole genomes of two affected kittens were sequenced and compared to 82 existing cat genomes. Both BSH kittens had homozygous insertions of an adenine within exon 3 of the FAS-ligand gene. The resultant frameshift and premature stop codon were predicted to result in a severely truncated protein that is unlikely to be able to activate FAS. Three additional affected BSH kittens were homozygous for the variant, while 11 of 16 unaffected, but closely related, BSH cats were heterozygous for the variant. All BSH cats in the study were from a population with significant inbreeding. The variant was not identified in a further survey of 510 non-BSH cats. Identification of a genetic defect in the FAS-mediated apoptosis pathway confirms that the lymphoproliferative disease in BSH cats fulfills the diagnostic criteria for ALPS in humans. These results will enable the development of a genetic test to detect BSH carrier animals.",
author = "Danielle Aberdein and Munday, {John S.} and Barbara Gandolfi and Dittmer, {Keren E.} and Richard Malik and Garrick, {Dorian J.} and Lyons, {Leslie A.} and {99 Lives Consortium}, {Lives Consortium} and Alves, {Pauol C.} and Barsh, {Gregory S.} and Beale, {Holly C.} and Boyko, {Adam R.} and Castelhano, {Marta G.} and Patricia Chan and Ellinwood, {N. Matthew} and Helps, {Christopher R.} and Kaelin, {Christopher B.} and Tosso Leeb and Hannes Lohi and Maria Longeri and Montague, {Michael J.} and Murphy, {William J.} and Pedersen, {Niels C.} and Rothschild, {Max F.} and Swanson, {William F.} and Terio, {Karen A.} and Todhunter, {Rory J.} and Warren, {Wesley C.}",
note = "Funding Information: Funding was provided by the National Center for Research Resources R24 RR016094, and is currently supported by the Office of Research Infrastructure Programs/OD R24OD010928, the University of Missouri ??? Columbia Gilbreath-McLorn Endowment, the Winn Feline Foundation (W10-014, W11-041, MT13-010), the Phyllis and George Miller Trust (MT08-015), the University of California ??? Davis, Center for Companion Animal Health (2008-36-F, 2008-06-F), and the Cat Health Network (D12FE-510) (LAL). Richard Malik is supported by the Valentine Charlton Bequest. The authors wish to thank the veterinarians who dealt with these cases over the years: Sue Foster, David Church, and especially Hugh Bain, who facilitated getting detailed information from a key breeder in Australia who provided many of the critical specimens; and Lydia Tong and Mark Krockenberger who provided necropsy and histology for the Australian cats. Funding for the 99 Lives Cat Genome Sequencing Initiative has been provided by the Winn Feline Foundation and the George Sydney and Phyllis Redman Miller Trust (MT???13-010), the National Geographic Society Education Foundation (2P-14), the University of Missouri Gilbreath-McLorn Endowment (LAL), contributions from the 99 Lives Consortium participants, donations from Associazione Nazionale Felina Italiana, Zoetis, Orivet Genetic Pet Care, Langford Veterinary Services, the World Cat Federation, and public donations. The authors appreciate the provision of cat DNA samples by Cristy Bird, Bruno Chomel, Kyung Sik Kim, Nassem N. Naimi of Best Friend Veterinary Clinic in Amman, Jordan, Julie Pomerantz, John Snape, Susanne and Claus Wehnert, Nancy Carpenter at Utah???s Hogle Zoo, Ashleigh Lutz-Nelson at San Francisco Zoo & Gardens, and Julie Feinstein at the American Museum of Natural History. Pauol C. Alves (CIBIO/InBIO, Centro de Investiga????o em Biodiversidade e Recursos Gen??ticos, Universidade do Porto, Campus Agr??rio de Vair??o, 4485???661, Vair??o, Portugal; Departamento de Biologia, Faculdade de Ci??ncias da Universidade do Porto (FCUP), 4169-007 Porto, Portugal; Wildlife Biology Program, University of Montana, Missoula, Montana 59812, USA); Gregory S. Barsh (HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA; Department of Genetics, Stanford University, Stanford, California, 94305 USA); Holly C. Beale (Maverix Biomics, Inc., San Mateo, California, 94402 USA); Adam R. Boyko (Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, 14853 USA); Marta G. Castelhano (Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, 14853 USA); Patricia Chan (Maverix Biomics, Inc., San Mateo, California, 94402 USA); N. Matthew Ellinwood (Department of Animal Science, College of Agriculture and Life Sciences, Iowa State University, Ames, Iowa, 50011 USA); Christopher R. Helps (Langford Veterinary Services, University of Bristol, Langford, Bristol, BS40 5DU UK); Christopher B. Kaelin (HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA; Department of Genetics, Stanford University, Stanford, California, 94305 USA); Tosso Leeb (Vetsuisse Faculty, Institute of Genetics, University of Bern, Bern, Switzerland. Swiss Competence Center of Animal Breeding and Genetics, University of Bern, 3001, Bern University of Applied Sciences HAFL & Agroscope, 3001, Bern, Switzerland); Hannes Lohi (Department of Veterinary Biosciences and Research Programs Unit, Molecular Neurology, University of Helsinki and Folkh??lsan Research Center, Helsinki 00014, Finland); Maria Longeri (Dipartimento di Scienze Veterinarie e Sanit?? Pubblica, University of Milan, 20122 Milan, Italy); Michael J. Montague (The Genome Institute, Washington University School of Medicine, St. Louis, Missouri, 63108 USA); William J. Murphy (Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, 77845 USA); Niels C. Pedersen (Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California at Davis, Davis, California, 95616 USA); Max F. Rothschild (Department of Animal Science, College of Agriculture and Life Sciences, Iowa State University, Ames, Iowa, 50011 USA); William F. Swanson (Center for Conservation and Research of Endangered Wildlife (CREW), Cincinnati Zoo & Botanical Garden, Cincinnati, Ohio, 45220 USA); Karen A. Terio (Zoological Pathology Program, University of Illinois, Maywood, IL 60153); Rory J. Todhunter (Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, 14853 USA); Wesley C. Warren (Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, 77845 USA). Publisher Copyright: {\textcopyright} 2016, Springer Science+Business Media New York.",
year = "2017",
month = feb,
day = "1",
doi = "10.1007/s00335-016-9668-1",
language = "English (US)",
volume = "28",
pages = "47--55",
journal = "Mammalian Genome",
issn = "0938-8990",
publisher = "Springer",
number = "1-2",
}