Seeking to solve the insoluble feline amyloidosis riddle

Amyloidosis is an unresolved and recurrent disease in the history of cat breeding. The disease appears in periodic waves worldwide likely because no in vivo diagnostic tool is available. The disease onset is extremely variable and the syndrome is characterized by the abnormal presence of a proteic complex, positive to Congo Red, that accumulates in target tissues. This build-up eventually affects organ function and leads to the animal's death. The disease is documented in wild felids1 and in fancy breeds such as Abyssinian/Somali2 and Siamese/Oriental. In the Abyssinian/Somali group, the disease is characterized by the presence of renal deposits of amyloid, while in the Siamese/Oriental group, deposits in the liver are detected. In man, several types of inherited amyloidosis are caused by single gene variants. The mode of inheritance in the domestic cat is still unclear. To identify the causal DNA variant(s) associated with the syndrome, a case-control genome-wide association study was performed. Over 130 samples (90 Siamese/Oriental and 44 Abyssinian/Somali) were ascertained from several countries. Genomic DNA was extracted from tissues of cats with post mortem positive reports for amyloidosis (ages than 6 years, affected) and with post mortem negative report (aqe z than 7 years, controls). The genome-wide association study was performed using the data obtained from the Illumina feline 63K array. Preliminary analyses in Siamese/Oriental cohort, showed an association of the trait within a coding region of chromosome Al, while in Abyssinian/Somali an association with chromosome D2 was detected, within a 3.5 Mb haplotype block. Genomic results are supported by the results of a shotgun proteomic approach of the proteic deposits.