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Research article2021Peer reviewedOpen access

Multi-omic analyses in Abyssinian cats with primary renal amyloid deposits

Genova, Francesca; Nonnis, Simona; Maffioli, Elisa; Tedeschi, Gabriella; Strillacci, Maria Giuseppina; Carisetti, Michela; Sironi, Giuseppe; Cupaioli, Francesca Anna; Di Nanni, Noemi; Mezzelani, Alessandra; Mosca, Ettore; Helps, Christopher R.; Leegwater, Peter A. J.; Dorso, Laetitia; Longeri, Maria; Buckley, Reuben M.; Aberdein, Danielle; Alves, Paulo C.; Andersson, Asa Ohlsson; Barsh, Gregory S.;
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Abstract

The amyloidoses constitute a group of diseases occurring in humans and animals that are characterized by abnormal deposits of aggregated proteins in organs, affecting their structure and function. In the Abyssinian cat breed, a familial form of renal amyloidosis has been described. In this study, multi-omics analyses were applied and integrated to explore some aspects of the unknown pathogenetic processes in cats. Whole-genome sequences of two affected Abyssinians and 195 controls of other breeds (part of the 99 Lives initiative) were screened to prioritize potential disease-associated variants. Proteome and miRNAome from formalin-fixed paraffin-embedded kidney specimens of fully necropsied Abyssinian cats, three affected and three non-amyloidosis-affected were characterized. While the trigger of the disorder remains unclear, overall, (i) 35,960 genomic variants were detected; (ii) 215 and 56 proteins were identified as exclusive or overexpressed in the affected and control kidneys, respectively; (iii) 60 miRNAs were differentially expressed, 20 of which are newly described. With omics data integration, the general conclusions are: (i) the familial amyloid renal form in Abyssinians is not a simple monogenic trait; (ii) amyloid deposition is not triggered by mutated amyloidogenic proteins but is a mix of proteins codified by wild-type genes; (iii) the form is biochemically classifiable as AA amyloidosis.

Published in

Scientific Reports
2021, Volume: 11, number: 1, article number: 8339Publisher: NATURE RESEARCH