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

  • Author(s): 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
  • 99 Lives Consortium
  • Longeri, Maria
  • et al.
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.

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