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.

Details

Title
Multi-omic analyses in Abyssinian cats with primary renal amyloid deposits
Author
Genova, Francesca 1 ; Nonnis Simona 1 ; Maffioli Elisa 1 ; Tedeschi, Gabriella 1 ; Strillacci Maria Giuseppina 1 ; Carisetti Michela 1 ; Sironi Giuseppe 1 ; Cupaioli, Francesca Anna 2 ; Di Nanni Noemi 2 ; Mezzelani Alessandra 2 ; Mosca Ettore 2 ; Helps, Christopher R 3 ; Leegwater Peter A J 4 ; Dorso Laetitia 5 ; Buckley, Reuben M 6 ; Aberdein Danielle 7 ; Alves, Paulo C 8 ; Andersson, Asa Ohlsson 9 ; Barsh, Gregory S 10 ; Bellone, Rebecca R 11 ; Bergström, Tomas F 12 ; Boyko, Adam R 13 ; Brockman, Jeffrey A 14 ; Casal, Margret L 15 ; Castelhano, Marta G 16 ; Distl Ottmar 17 ; Dodman, Nicholas H 18 ; Matthew, Ellinwood N 19 ; Fogle, Jonathan E 20 ; Forman, Oliver P 21 ; Garrick, Dorian J 22 ; Ginns, Edward I 23 ; Haase Bianca 24 ; Häggström Jens 9 ; Harvey, Robert J 25 ; Hasegawa Daisuke 26 ; Hernandez, Isabel 27 ; Hytönen, Marjo K 28 ; Kaukonen, Maria 28 ; Kaelin, Christopher B 10 ; Kosho Tomoki 29 ; Leclerc Emilie 30 ; Lear, Teri L 31 ; Leeb Tosso 32 ; Li Ronald H L 33 ; Lohi Hannes 28 ; Magnuson, Mark A 34 ; Malik, Richard 35 ; Mane, Shrinivasrao P 36 ; Munday, John S 7 ; Murphy, William J 37 ; Pedersen, Niels C 38 ; Peterson-Jones, Simon M 39 ; Rothschild, Max F 40 ; Rusbridge Clare 41 ; Shapiro, Beth 42 ; Stern, Joshua A 38 ; Swanson, William F 43 ; Terio, Karen A 44 ; Todhunter, Rory J 16 ; Warren, Wesley C 45 ; Wilcox, Elizabeth A 16 ; Wildschutte, Julia H 46 ; Yu, Yoshihiko 26 ; Lyons, Leslie A 6 ; Longeri, Maria 1 

1  University of Milan, Department of Veterinary Medicine, Lodi, Italy (GRID:grid.4708.b) (ISNI:0000 0004 1757 2822) 
2  National Research Council of Italy (CNR-ITB), Institute of Biomedical Technologies, Segrate, Italy (GRID:grid.5326.2) (ISNI:0000 0001 1940 4177) 
3  University of Bristol, Langford Vets, Langford, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
4  Utrecht University, Department of Clinical Sciences of Companion Animals, Utrecht, The Netherlands (GRID:grid.5477.1) (ISNI:0000000120346234) 
5  Ecole Nationale Vétérinaire Oniris, Pathology Service for Large Animals, Nantes, France (GRID:grid.5477.1) 
6  University of Missouri, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, Columbia, USA (GRID:grid.134936.a) (ISNI:0000 0001 2162 3504) 
7  Massey University, School of Veterinary Science, Palmerston North, New Zealand (GRID:grid.148374.d) (ISNI:0000 0001 0696 9806) 
8  Universidade Do Porto, CIBIO/InBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos/InBIO Associate Lab & Faculdade de Ciências, Vila do Conde, Portugal (GRID:grid.5808.5) (ISNI:0000 0001 1503 7226); University of Montana, Wildlife Biology Program, Missoula, USA (GRID:grid.253613.0) (ISNI:0000 0001 2192 5772) 
9  Swedish University of Agricultural Sciences, Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Uppsala, Sweden (GRID:grid.6341.0) (ISNI:0000 0000 8578 2742) 
10  HudsonAlpha Institute for Biotechnology, Huntsville, USA (GRID:grid.417691.c) (ISNI:0000 0004 0408 3720); Stanford University, Department of Genetics, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
11  University of California - Davis, Veterinary Genetics Laboratory, Davis, USA (GRID:grid.27860.3b) (ISNI:0000 0004 1936 9684); University of California - Davis, Department of Population Health and Reproduction, Davis, USA (GRID:grid.27860.3b) (ISNI:0000 0004 1936 9684) 
12  Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics, Uppsala, Sweden (GRID:grid.6341.0) (ISNI:0000 0000 8578 2742) 
13  Cornell University, Department of Biomedical Sciences, College of Veterinary Medicine, Ithaca, USA (GRID:grid.5386.8) (ISNI:000000041936877X) 
14  Hill’s Pet Nutrition Inc, Topeka, USA (GRID:grid.418753.c) (ISNI:0000 0004 4685 452X) 
15  University of Pennsylvania, Reproduction, and Pediatrics, School of Veterinary Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
16  Cornell University, Department of Clinical Sciences, College of Veterinary Medicine, Ithaca, USA (GRID:grid.5386.8) (ISNI:000000041936877X) 
17  University of Veterinary Medicine Hannover, Institute for Animal Breeding and Genetics, Hannover, Germany (GRID:grid.412970.9) (ISNI:0000 0001 0126 6191) 
18  Cummings School of Veterinary Medicine, Tufts University, Department of Clinical Sciences, Grafton, USA (GRID:grid.429997.8) (ISNI:0000 0004 1936 7531) 
19  National MPS Society, Durham, USA (GRID:grid.484506.b) 
20  North Carolina State University, Department of Population Health and Pathobiology, College of Veterinary Medicine, Raleigh, USA (GRID:grid.40803.3f) (ISNI:0000 0001 2173 6074) 
21  WALTHAM Centre for Pet Nutrition, Leicestershire, UK (GRID:grid.435741.0) (ISNI:0000 0004 0597 4939) 
22  Massey University, AL Rae Centre of Genetics and Breeding, Palmerston North, New Zealand (GRID:grid.148374.d) (ISNI:0000 0001 0696 9806) 
23  University of Massachusetts Medical School, Department of Psychiatry, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364) 
24  University of Sydney, Sydney School of Veterinary Science, Faculty of Science, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
25  University of the Sunshine Coast, School of Health and Behavioural Sciences, Sippy Downs, Australia (GRID:grid.1034.6) (ISNI:0000 0001 1555 3415) 
26  Nippon Veterinary and Life Science University, Laboratory of Veterinary Radiology, Musashino, Japan (GRID:grid.412202.7) (ISNI:0000 0001 1088 7061) 
27  Cornell University, Pediatrics and Medical Genetics Service, College of Veterinary Medicine, Ithaca, USA (GRID:grid.5386.8) (ISNI:000000041936877X) 
28  University of Helsinki and Folkhälsan Research Center, Department of Veterinary Biosciences; Department of Medical and Clinical Genetics, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
29  Shinshu University School of Medicine, Department of Medical Genetics, Matsumoto, Nagano, Japan (GRID:grid.263518.b) (ISNI:0000 0001 1507 4692) 
30  SPF, Symrise Group, Elven, France (GRID:grid.263518.b) 
31  University of Kentucky - Lexington, Department of Veterinary Science, Lexington, USA (GRID:grid.266539.d) (ISNI:0000 0004 1936 8438) 
32  University of Bern, Vetsuisse Faculty, Institute of Genetics, Bern, Switzerland (GRID:grid.5734.5) (ISNI:0000 0001 0726 5157) 
33  University of California Davis, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, Davis, USA (GRID:grid.27860.3b) (ISNI:0000 0004 1936 9684) 
34  Vanderbilt University, Departments of Molecular Physiology and Biophysics, Cell and Developmental Biology, and Medicine, School of Medicine, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217) 
35  University of Sydney, Centre for Veterinary Education, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
36  Elanco Animal Health, Greenfield, USA (GRID:grid.414719.e) (ISNI:0000 0004 0638 9782) 
37  Texas A&M University, Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, College Station, USA (GRID:grid.264756.4) (ISNI:0000 0004 4687 2082) 
38  University of California Davis, Department of Medicine and Epidemiology, School of Veterinary Medicine, Davis, USA (GRID:grid.27860.3b) (ISNI:0000 0004 1936 9684) 
39  Michigan State University, Small Animal Clinical Sciences, College of Veterinary Medicine, East Lansing, USA (GRID:grid.17088.36) (ISNI:0000 0001 2150 1785) 
40  Iowa State University, Department of Animal Science, College of Agriculture and Life Sciences, Ames, USA (GRID:grid.34421.30) (ISNI:0000 0004 1936 7312) 
41  University of Surrey, School of Veterinary Medicine, Faculty of Health & Medical Sciences, Guildford, UK (GRID:grid.5475.3) (ISNI:0000 0004 0407 4824) 
42  University of California Santa Cruz, Department of Ecology and Evolutionary Biology, Santa Cruz, USA (GRID:grid.205975.c) (ISNI:0000 0001 0740 6917) 
43  Center for Conservation and Research of Endangered Wildlife (CREW), Cincinnati, USA (GRID:grid.27860.3b) 
44  University of Illinois, Zoological Pathology Program, Brookfield, USA (GRID:grid.185648.6) (ISNI:0000 0001 2175 0319) 
45  University of Missouri, Division of Animal Sciences, College of Agriculture, Food and Natural Resources, School of Medicine, Columbia, USA (GRID:grid.134936.a) (ISNI:0000 0001 2162 3504) 
46  Bowling Green State University, Department of Biological Sciences, Bowling Green, USA (GRID:grid.253248.a) (ISNI:0000 0001 0661 0035) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-021-87168-0
ProQuest document ID
2513413290
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.