Genomic localization and genetic characterization of amyloidosis in Abyssinian and Siamese cats

Amyloidosis is a rare disorder which occurs in different species including humans, chickens and wild and domestic felids. The disease is characterized by the abnormal deposition of amyloid proteins in organs or tissues causing different associated maladies. Feline amyloidosis can be inherited or acquired, often secondary to chronic inflammatory processes and is reported in Siamese/Oriental (Fig.1A) and in Abyssinian/Somali (Fig.1B) cats. In these breeds, the accumulation of amyloid occurs mainly in kidney for the Abyssinians and in the liver for the Siamese. Amyloidosis diagnosis is obtained definitively only by a specific histological staining, as the affected tissues are positive to Congo Red. The genetic cause underlying the feline conditions are still unknown, no DNA tests are available and the mode of inheritance of the disorder is still unclear in felines. To genetically localize the locus or loci, 26 affected Abyssinian cases and 21 Abyssinian controls were genotyped on a high-density array. Associations were obtained with cat chromosome B4 and C2, and candidate genes were visually explored within these regions. Subsequently, whole genome sequencing was performed on two Abyssinian and two Siamese affected cats and added to the 99 Lives Project, to allow the effective screening of possible causative variants associated with the disorder. A further analysis of the sequences available for the affected cats, confirmed the presence of mutations within the candidate genes and within other genes. Screening all the variants in all the chromosomes led to 51 SNPs for the Abyssinians and 15 SNPs for the Siamese. The genotyping of the variants identified in the WGS affected cats (Abyssinian and Siamese) was performed on all available samples as well as on a population of breeds and random bred cats to confirm the association with the disorder. These preliminary results could be promising in the reconstruction of the Amyloidosis pathological pathways