Multi-omic analyses in Abyssinian cats with primary renal amyloid deposits.
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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.
author list (cited authors)
Genova, F., Nonnis, S., Maffioli, E., Tedeschi, G., Strillacci, M. G., Carisetti, M., ... Longeri, M.
complete list of authors
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 AJ||Dorso, Laetitia||Longeri, Maria