Feline Amyloidosis : new genomic and proteomic approaches for an old and current disorder

Amyloidosis is a disorder wherein amyloid proteins are abnormally deposited in organs, causing secondary health complications. In humans, eight genes cause different forms of amyloidosis. In Abyssinian / Somali and Siamese / Oriental cats, juvenile amyloidosis has been reported as familial. After being a significant health concern in Abyssinians in the recent past, the disease is now emerging in Siamese / Orientals worldwide, however with different pathogenesis. Abyssinians tend to succumb to renal disease while Siamese tend to succumb to hepatic disease. As the pathogenesis of feline amyloidosis is unknown, the onset of symptoms unpredictable, and biopsy confirmation of disease unreliable, a genomic and proteomic approach was designed to clarify the mechanisms and to find the genetic basis of the disease. Genomic DNA from 22 Abyssinian / Somali and 23 Siamese / Oriental, all with post mortem positive reports for amyloidosis, ages ≤ than 6 years and an equal number of controls with post mortem negative reports, ages ≥ than 7 years, was extracted from tissues of cats bred in Europe, USA and Australia. To inspect population stratification of cats from the different countries, 148 unlinked SNP markers will be genotyped using Sequenom MassARRAY technology to further support the selection of controls and the combined analysis of the cats from different regions. A preliminary genome-wide association will be performed using the Illumina feline 63K array on 48 samples to identify the regions harboring causative genes. Moreover, to characterize the main proteic components, samples from massive deposits and corresponding normal tissues have been digested. A mass spectrometric strategy for in-depth protein sequencing has been applied, shotgun proteomics, using the ThermoFisher LTQ Orbitrap Velos ETD equipped with Nano HPLC Ultimate 3000, which is ideally suited for discovery-driven profiling and can achieve the identification of different proteins from a biological sample.