Aberdein, Danielle; Munday, John S; Gandolfi, Barbara; Dittmer, Keren E; Malik, Richard; Garrick, Dorian J; Lyons, Leslie A; 99 Lives, Consortium (2017). A FAS-ligand variant associated with autoimmune lymphoproliferative syndrome in cats. Mammalian genome, 28(1-2), pp. 47-55. Springer-Verlag 10.1007/s00335-016-9668-1
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Aberdein_2017_99Lives_Consortium_Mamm_Genome_28_47_55.pdf - Published Version Available under License Publisher holds Copyright. Download (1MB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics 05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 590 Animals (Zoology) 600 Technology > 610 Medicine & health |
ISSN: |
0938-8990 |
Publisher: |
Springer-Verlag |
Language: |
English |
Submitter: |
Tosso Leeb |
Date Deposited: |
20 Sep 2019 14:32 |
Last Modified: |
10 May 2022 16:42 |
Publisher DOI: |
10.1007/s00335-016-9668-1 |
PubMed ID: |
27770190 |
Additional Information: |
Tosso Leeb: member of 99 Lives Consortium |
BORIS DOI: |
10.7892/boris.133169 |
URI: |
https://boris.unibe.ch/id/eprint/133169 |
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