Munis Dundar, Kevan M.A. Gartland and Peter B. Gahan
Kevan M.A. Gartland and Jill S. Gartland
Biotechnology, including genetic modifications, can play a vital role in helping to meet future food and environmental security needs for our growing population. The nature and use of biotechnology crops are described and related to aspects of food security. Biotechnological applications for food and animal feed are described, together with trends on global adoption of these crops. The benefits of biotechnology crops through increased yield, reduced pesticide use and decreased environmental damage are discussed. Examples of biotechnology crops which do not involve genetic modification are also described. Applications of biotechnology to drought and salt tolerance, and biofortification in which micronutrient content is enhanced are discussed. Emergent technologies such as RNA spraying technology, use of genome editing in agriculture and future targets for improved food and environmental security are considered.
Laura Paneghetti, Andrea Gallotta, Chiara Parrozzani and Giorgio Fassina
The ageing process in the European society will become one of the key driving forces of change over the next decades. The specific demands of older generations constitute a key market of the future, and the pressure to improve and expand health services increases, especially as far as chronic diseases, such as cancer. Availability of cost effective cancer early detection protocols, based on predictive biomarkers, will improve patients management reducing consequently the high costs associated to treating patients when the disease is at an advanced stage.
Elena Manara, Andi Abeshi and Matteo Bertelli
MAGI is concerned with research and diagnosis of rare genetic diseases. It has been operating since 2006 in Italy and abroad. Today it has three centers in Italy, including a medical genetics laboratory specialized in next generation sequencing in Bolzano, a medical genetics laboratory specialized in MLPA in Rovereto (Trento) and a genetic diseases information center at San Felice del Benaco (Brescia). MAGI has also invested outside Italy, setting up non-profit genetics laboratories in countries such as Albania, Russia and in the near future, Kazakhstan.
Sandro Michelini, Mrco Cardone, Paolo Maltese, Alice Bruson, Alessandro Fiorentino and Matteo Bertelli
Primary lymphedema can be familial (in which more than one member of the same family has a lymphedema phenotype), syndromic (in which lymphedema is one symptom of a complex clinical syndrome) or sporadic (in which an isolated family member has lymphedema). All types of lymphedema are determined by genetic alteration of one or more genes. Not all the genes involved are known.
Elena Manara, Paolo E. Maltese, Giulia Guerri, Giuseppe Marceddu, Natale Capodicasa, Andi Abeshi and Matteo Bertelli
Molecular diagnosis relieves patients of uncertainty, aids informed decisions about health and reproductive choices, and helps them join clinical trials or access available therapy. Genetic testing by next generation sequencing (NGS) is the suggested choice for a wide variety of disorders with heterogeneous phenotypes, alleles and loci. The development of a NGS service at MAGI Balkans, through the support of a partner, increases the availability of forefront genetic testing in Albania with great advantages for patients and their families. Here we report the NGS tests performed in collaboration with MAGI Euregio, Italy, for the diagnosis of rare genetic disease in seven probands and their families. The diseases/manifestations included ichthyosis, familial adenomatous polyposis, diabetes, syndromic craniosynostosis, fronto-temporal dementia, fragile X syndrome and ataxia. We obtained an overall detection rate of 57%. For 4/7 probands we identified a pathogenic or likely pathogenic variant, while for the others, the results did not completely explain the phenotype. All variants were confirmed by Sanger sequencing. Segregation of the variant with the affected phenotype was also evaluated.
Vanna Micheli and Matteo Bertelli
Lesch-Nyhan Disease (LND) is a rare X-linked genetic disease with hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency, due to mutation in the encoding gene, located on the X-chromosome. LND patients exhibit hyperuricemia with stones due to unrecycled purine accumulation and increased synthesis, and a devastating neurological syndrome with dystonia and self-injurious behaviour, choreoathetosis and spasticity. In spite of biochemical and molecular research, the fine connection between the neurological syndrome and HGPRT deficiency is still unclear, though there is consensus regarding brain neurotransmitter dysfunction with few dopaminergic neuron terminals in the striatum. The rarity of the disease makes it difficult to obtain homogeneous population of patients to study. The aim of this paper is to contribute to the understanding of the connection between genotype and phenotype in a cohort of Italian patients, to propose a reliable method of identifying carrier women in affected families, and to provide evidence of a possible link between HGPRT deficiency and altered adenosinergic and serotonergic neurotransmission. Biochemical and mutation analysis is reported in 28 LNS Italian patients from 25 families, with virtually no HGPRT activity and typical LNS phenotype. Genetic analysis identified 24 HPRT mutations, nine of which had never previously been reported, and no mutation hotspots. Carrier females were identified by a new semiquantitative real-time PCR. Studies performed by real-time PCR on knockout mice demonstrated altered adenosinergic and serotonergic pathways, with greatly increased ADORA1A receptor expression, slightly decreased ADORA2A expression and unchanged ADORA2B expression. Increased HTRC2 expression with no significant difference in mRNA editing suggested serotonergic involvement. The different approaches used allowed us to study certain aspects of LND, focusing on mutation analysis in patients and carriers and on simultaneous analysis of biochemical and genetic features. Mouse models elucidated the possible involvement of adenosine and serotonine receptors in the neurotransmission aberration occurring in HGPRT deficiency.
Antonietta R. Silini and Ornella Parolini
A goal of regenerative medicine is to repair and regenerate damaged cells, tissues, and organs and ultimately restore function. Regeneration can be obtained by cell replacement or by stimulating the body’s own repair mechanisms. It requires a favorable microenvironment so that regenerative signals can stimulate resident stem/stromal cells. Regeneration is only possible after resolution of injury-induced inflammation. Immune response may be aggravated in degenerative, inflammation-based diseases. In this mini-review we discuss how cells isolated from the amniotic membrane of human term placentas and their derivatives, such as conditioned cell culture medium, can help resolve many diseases characterized by altered immune response by acting on different inflammatory mediators. Amniotic cells and derivatives have a wide spectrum of immunomodulatory properties that help trigger tissue regeneration. They can promote resolution of injury-related inflammation by reducing pro-inflammatory signals and favoring anti-inflammatory immune components. The multifaceted, immunomodulatory properties of amniotic membrane-derived cells and derivatives make them attractive for a variety of applications, especially in diseases with an exacerbated immune response, such as degenerative, inflammatory- based diseases.
Letizia Mazzini, Fabiola De Marchi, Lucia Corrado and Sandra D’Alfonso
Amyotrophic lateral sclerosis, also known as motor neuron disease or Lou Gehrig’s disease, is an adult-onset neurodegenerative disease that targets motor neurons in the spinal cord, cortex and brain stem. Selective degeneration of corticospinal (upper) and spinal (lower) motor neurons manifests as a linear decline in muscular function, eventually resulting in paralysis, speech and swallowing deficits and death, usually from impaired respiratory function, over a time course of approximately 3-5 years.
Liborio Stuppia and Valentina Gatta
Approximately 15% of couples in western countries have infertility problems. Identification of genetic alterations responsible for infertility is important for therapy and to avoid transmission of genetic abnormalities that could impair the health of offspring, especially for couples with idiopathic infertility and those undergoing assisted reproductive techniques (ART). The aim of this review is to summarize the main genetic tests to offer to infertile couples during diagnostic work-up and in cases of ART, considering future directions of risk assessment in the field of reproductive medicine. Before offering a genetic test to an infertile couple, it is crucial to characterize their clinical and hormonal profile. Genetic testing should only be carried out when appropriate, that is when clinical and family history suggest a genetic cause of infertility. The genetic tests to offer to infertile couples must be targeted at infertility and should always consider the cost/benefit ratio. No causative genes have been identified for certain conditions, making clinical genetic testing impractical. Next generation sequencing (NGS) is a powerful tool for the identification of pathological mutations and for discovering new disease-associated loci in the field of reproduction. Comprehensive multigene panels for infertile risk assessment could simplify the diagnostic and therapeutic process. The main limitation is interpretation of the enormous amount of NGS data, since the clinical role and biological implications of variants, especially those of unknown significance, are still unclear.