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A FAS-ligand variant associated with autoimmune lymphoproliferative syndrome in cats
- Source :
- 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
- Publication Year :
- 2017
- Publisher :
- Springer-Verlag, 2017.
-
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.
- Subjects :
- 0301 basic medicine
Fas Ligand Protein
Population
610 Medicine & health
Apoptosis
Biology
medicine.disease_cause
Fas ligand
Frameshift mutation
03 medical and health sciences
Exon
Genetics
medicine
Animals
Humans
Lymphocytes
fas Receptor
education
Frameshift Mutation
Gene
Mutation
education.field_of_study
CATS
Genome
Whole Genome Sequencing
Autoimmune Lymphoproliferative Syndrome
medicine.disease
030104 developmental biology
Codon, Nonsense
Autoimmune lymphoproliferative syndrome
Immunology
Cats
570 Life sciences
biology
590 Animals (Zoology)
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- 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 <http://dx.doi.org/10.1007/s00335-016-9668-1>
- Accession number :
- edsair.doi.dedup.....fbe2ef4e3b40c1c6c8fb328ff70d92e4
- Full Text :
- https://doi.org/10.7892/boris.133169