Genova/Longeri

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PhD Student: Francesca Genova

Francesca Genova, MSc, graduated in Veterinary Biotechnological Science in July 2016 at the University of Milan, with full marks and honors. Her thesis concerned the study of potential biomarkers in the canine oral cavity melanoma and was entitled “LTA4H and FXR1 gene expression analyses for canine oral cavity melanoma metastasis in FFPE samples”. She obtained the Bachelor’s Degree in Veterinary Biotechnology in July 2014 at the University of Milan with the thesis “Test assembling and genetic screening for the Muchopolysaccaridosis VI in the Birman cat” that led to the publication of a scientific paper (Lyons et al., 2016 BMC Veterinary Research, 12:136. DOI: 10.1186/s12917-016-0764-y). The research field in which she is involved is mainly focused on genetic diseases and genomic analyses, but it is integrated in a multidisciplinary and translational approach which includes proteomics, pathology and histology.

 

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Tutor: Prof. Maria Longeri

Maria Longeri, DVM, PhD, is Associate Professor of Animal breeding and Genetics at DiMeVet-UNIMI since 2005, and passed the National Academic Qualification as Full Professor in 2014. She participated to the first bovine genome mapping (EU project - BovMap) and she has been unit leader of two National projects (PRIN-MIUR 2003 and PRIN-MIUR 2006). During her academic carrier she experienced researches in genetics of immune response and genetics/genomics of the inherited diseases both in farm animals and in pets. She is holder of two patents and among other works, she has helped the identification of the causative mutation of the Ichtyosis in Chianina cattle using the first bovine high-density SNP panel in Genome Wide Analysis and has been co-author of its publication in Nature Genetics.  Introducing the study of the cat genetics and genomics in Italy at Academic level, she has been co-founder of the “Osservatorio Veterinario  Italiano Cardiopatie del cane e del gatto” and of the UNIMI-Spin-off Vetogene. She is Member of the Standing Committee “Applied Genetics of Companion Animals” of the International Society of Animal Genetics (terms 2014-2019).

PROJECT DESCRIPTION:

Next generation genomic and proteomic analyses in Feline Amyloidosis.

Amyloidosis is a rare disorder which occurs in many species including humans, chickens, bovine, domestic and wild felids. The disease is determined by abnormal depositions of “Amyloid” proteins in organs or tissues causing different harms. Feline Amyloidosis can be inherited or acquired (often secondary to chronic inflammatory processes), but the pathogenesis remains unknown, the onset of symptoms is unpredictable and the diagnosis is only possible by post-mortem evidence of huge Amyloid deposits in single organs or systemically. In humans, at least eight causative single genes have been identified as causative of different forms of Amyloidosis. In Felines, no causative genes are known, but in the Abyssinian/Somali and the Siamese/Oriental cat breeds, familial forms with storage of Amyloid, mainly in kidney and liver respectively, have been reported. The affected animals suddenly and unpredictably fall ill and quite rapidly die at a young age. The in vivo diagnosis could be performed by biopsy, however it might fail to notice the deposits. A certain diagnosis is only obtained when histological tissue preparations are positive to Congo Red, a specific stain with high affinity for Amyloid. No clinical exams and no DNA tests are available for the Amyloidosis diagnosis at the moment.

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The main objectives of our project are:

1) Developing of protocols that allow a good DNA extraction from the specimens in order to make the Formalin – Fixed, Paraffin – Embedded samples (FFPE) archives, gold mines of additional case samples.

2) GWAS analyses by running the cohorts of cases and controls on a new large Feline SNP DNA chip array (about 400.000 SNPs).

3) Sequencing the whole genome of two Siamese/Oriental and two Abyssinian/Somali to identify mutations in the candidate regions. The variants identified will be prioritized and priority will be given to variants that: a) map in genes that are both causative or candidate in other species, b) underlay up/down – regulated proteins in the deposits and c) are homozygous in affected cats, but heterozygous or wild-type in unaffected cats. 

4) Validating the more promising variants identified and screening of the cases and controls to find markers for diagnosis and selection. 

5) Performing a shotgun proteomic approach on Abyssinian/Somali and Siamese/Oriental both fresh and FFPE samples for Amyloid deposits characterization (this part will be performed by Prof. Tedeschi’s group – DIMEVET, UNIMI).

6) Matching the genomic and proteomic results to reconstruct the pathogenic molecular mechanism of Amyloidosis.

7) (Possibly) Designing tools for genetic screening.

The discovery of new potential biomarkers could represent a real turning point in the diagnosis and the treatment of the cat Amyloidosis disease. Moreover, genomic and proteomic approach to Feline Amyloidosis will provide important comparative information on human protein folding disorders.

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