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Identificazione di nuovi geni associati al fenotipo di Hirschsprung in C. Elegans e loro controparte umanaGoldoni, Alberto <1975> 12 June 2007 (has links)
No description available.
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Analisi di varianti strutturali e di sequenza in geni candidati per l'autismo sul cromosoma 2qCarone, Simona <1976> 12 June 2007 (has links)
No description available.
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DNA embrio-fetale nel sangue materno nel primo trimestre di gravidanzaCapone, Lucia <1978> 11 May 2007 (has links)
No description available.
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Analysis of TNFRSF5 gene mutations and splicing variants in CD40 receptor regulationCaraffi, Stefano Giuseppe <1977> 12 June 2007 (has links)
No description available.
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L'analisi di Linkage come metodo per la mappatura di malattie genetiche: studio di famiglie con paraparesi spastica ereditaria e anomalie del corpo callosoPippucci, Tommaso <1977> 12 June 2007 (has links)
No description available.
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Trapianto di cellule staminali autologhe geneticamente modificate per il trattamento di patologie metaboliche del fegato: approccio di terapia genica ex vivo per la sindrome di Crigler Najjar tipo IVenturi, Beatrice <1982> 07 June 2010 (has links)
No description available.
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Lo studio di famiglie con patologia genetica per l'identificazione del gene malattia: sindrome di mungan e trombocitopenia autosomica dominante (thc2)Castegnaro, Giovanni <1981> 07 June 2010 (has links)
No description available.
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Pathogenic mechanisms in mitochondrial optic neuropathiesMaresca, Alessandra <1982> 05 May 2011 (has links)
Leber’s hereditary optic neuropathy (LHON) and Autosomal Dominant Optic Atrophy (ADOA) are the two most common inherited optic neuropathies and both are the result of mitochondrial dysfunctions. Despite the primary mutations causing these disorders are different, being an mtDNA mutation in subunits of complex I in LHON and defects in the nuclear gene encoding the mitochondrial protein OPA1 in ADOA, both pathologies share some peculiar features, such a variable penetrance and tissue-specificity of the pathological processes.
Probably, one of the most interesting and unclear aspect of LHON is the variable penetrance. This phenomenon is common in LHON families, most of them being homoplasmic mutant. Inter-family variability of penetrance may be caused by nuclear or mitochondrial ‘secondary’ genetic determinants or other predisposing triggering factors.
We identified a compensatory mechanism in LHON patients, able to distinguish affected individuals from unaffected mutation carriers. In fact, carrier individuals resulted more efficient than affected subjects in increasing the mitochondrial biogenesis to compensate for the energetic defect. Thus, the activation of the mitochondrial biogenesis may be a crucial factor in modulating penetrance, determining the fate of subjects harbouring LHON mutations. Furthermore, mtDNA content can be used as a molecular biomarker which, for the first time, clearly differentiates LHON affected from LHON carrier individuals, providing a valid mechanism that may be exploited for development of therapeutic strategies. Although the mitochondrial biogenesis gained a relevant role in LHON pathogenesis, we failed to identify a genetic modifying factor for the variable penetrance in a set of candidate genes involved in the regulation of this process. A more systematic high-throughput approach will be necessary to select the genetic variants responsible for the different efficiency in activating mitochondrial biogenesis. A genetic modifying factor was instead identified in the MnSOD gene. The SNP Ala16Val in this gene seems to modulate LHON penetrance, since the Ala allele in this position significantly predisposes to be affected. Thus, we propose that high MnSOD activity in mitochondria of LHON subjects may produce an overload of H2O2 for the antioxidant machinery, leading to release from mitochondria of this radical and promoting a severe cell damage and death
ADOA is due to mutation in the OPA1 gene in the large majority of cases. The causative nuclear defects in the remaining families with DOA have not been identified yet, but a small number of families have been mapped to other chromosomal loci (OPA3, OPA4, OPA5, OPA7, OPA8). Recently, a form of DOA and premature cataract (ADOAC) has been associated to pathogenic mutations of the OPA3 gene, encoding a mitochondrial protein. In the last year OPA3 has been investigated by two different groups, but a clear function for this protein and the pathogenic mechanism leading to ADOAC are still unclear.
Our study on OPA3 provides new information about the pattern of expression of the two isoforms OPA3V1 and OPA3V2, and, moreover, suggests that OPA3 may have a different function in mitochondria from OPA1, the major site for ADOA mutations. In fact, based on our results, we propose that OPA3 is not involved in the mitochondrial fusion process, but, on the contrary, it may regulate mitochondrial fission. Furthermore, at difference from OPA1, we excluded a role for OPA3 in mtDNA maintenance and we failed to identify a direct interaction between OPA3 and OPA1. Considering the results from overexpression and silencing of OPA3, we can conclude that the overexpression has more drastic consequences on the cells than silencing, suggesting that OPA3 may cause optic atrophy via a gain-of-function mechanism. These data provide a new starting point for future investigations aimed at identifying the exact function of OPA3 and the pathogenic mechanism causing ADOAC.
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