A FAS-ligand variant associated with autoimmune lymphoproliferative syndrome in cats.
Mamm Genome
; 28(1-2): 47-55, 2017 02.
Article
en En
| MEDLINE
| ID: mdl-27770190
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Apoptosis
/
Receptor fas
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Proteína Ligando Fas
/
Síndrome Linfoproliferativo Autoinmune
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mamm Genome
Asunto de la revista:
GENETICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Nueva Zelanda