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Laboratory of Applied Biology to reproduction and development  

Laboratory of Applied Biology to reproduction and development

In our lab, we identify and characterize the genetic mutations associated with human disorders.

The preliminary identification is conducted by means of genome wide (GW) high throughput tools in collaboration with other groups. The further characterization is conducted with in vitro assays and by using the animal model zebrafish (Danio rerio). The main interests of the laboratory are reproduction and development.

 

Premature Ovarian Failure (POF) (Prof. Anna Marozzi)

Cessation of female reproductive function, at menopause, is associated with increased risk of age-related diseases including cardiovascular disease, osteoarthritis and osteoporosis. Premature Ovarian Failure (POF) has implications for women’s well-being as well as for fertility with an increasing clinical, social and economic impact. POF has an incidence of 1 in 10,000 women by age 20; 1 in 1,000 women by age 30; 1 in 100 women by age 40.The POF might be caused by different factors such as genetic factors, however, the majority of POF cases is still without explanation. The aim of the project is the study of molecular mechanisms responsible for POF through application of genome wide (GW) high throughput tools for identification of genes and risk-variants and elucidation of their function. Taking advantage of the technological advancements in genome research, such as the dense arrays to identify Single Nucleotide Polymorphisms (SNP), copy number (CNV) and gene expression variation and Next Generation Sequencing (NGS), we identify POF candidate genes. These genetic factors are further validated in vitro and in vivo in the zebrafish model and will be caused as a whole to develop a first generation diagnostic test for ovarian reserve. Indeed, a diagnosis of POF is nowadays possible only when amenorrhea is already established and the ovarian reserve is likely exhausted.

 

Functional analysis of human genes in zebrafish (Danio rerio

Zebrafish organs are functionally and morphologically similar to the human, so it was hoped that the use of this system might unveil mechanisms and pathways directly relevant to human disease and therapy. Until now, most zebrafish genes have been studied with regard to their roles in early embryonic development rather than to later organ formation. However, clinically, the phenotypes of many mutations do resemble common human disorders. Indeed, the effects of some mutations bear remarkable resemblance to human illness, thereby suggesting that diseases might be categorized as perturbations of evolutionarily conserved ontogenetic mechanisms. In addition, the mutant genes, once cloned, provide entrance points to critical disease pathways in medicine as in developmental biology. This model offers, among others, the possibility to interfere specifically with gene expression by injection of morpholino antisense oligomers. Although such defects are transient and not heritable, morpholinos can be used to assess the effects of diminishing function of orthologs of genes, including those known to be involved in human diseases.

 

Contacts

Prof. Anna Marozzi,
via Viotti 3/5, 20133 Milan, Italy
tel. +390250315845
anna.marozzi@unimi.it

 

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