1,721,109 research outputs found
A commentary on the novel complex allele [A238V; F508del] of the CFTR gene: clinical phenotype and possible implications for cystic fibrosis etiological therapies (INVITED)
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New era of cystic fibrosis: full mutational analysis and personalized therapy
Full text linkDespite its apparently simple genetics, cystic fibrosis (CF) is a rather complex genetic disease. A lot of variability in the steps of the path from the cystic fibrosis transmembrane conductance regulator (CFTR ) gene to the clinical manifestations originates an uncertain genotype - phenotype relationship. A major determinant of this uncertainty is the incomplete knowledge of the CFTR mutated genotypes, due to the high number of CFTR mutations and to the higher number of their combinations in trans and in cis. Also the very limited knowledge of functional effects of CFTR mutated alleles severely impairs our diagnostic and prognostic ability. The
final phenotypic modulation exerted by CFTR modifier genes and interactome further complicates the framework.
The next generation sequencing approach is a rapid, lowcost and high-throughput tool that allows a near complete structural characterization of CFTR mutated genotypes, as well as of genotypes of several other genes cooperating to the final CF clinical manifestations. This powerful method perfectly complements the new personalized therapeutic approach for CF. Drugs active on specific CFTR mutational classes are already available for CF patients or are in phase 3 trials. A complete genetic characterization has been becoming crucial for a correct personalized therapy. However, the need of a functional classification of each CFTR mutation potently arises. Future big efforts towards an ever more detailed knowledge of both structural and
functional CFTR defects, coupled to parallel personalized therapeutic interventions decisive for CF cure can be
foreseen
Reti trofiche a base detrito di 3 laghi dell'Italia Centrale: effetti per delezione di specie su struttura e funzione
No full textFunctional parameters are more affected by number and kind of taxa than are structural ones. The more complex system shows the greater stability resistance. -from English summar
Metodo per la determinazione di mutazioni del gene della Fibrosi Cistica
No full textLa presente invenzione concerne un metodo di rivelazione di mutazioni del gene CFTR (“Cystic Fibrosis Transmembrane Conductance Regulator”) della Fibrosi Cistica (FC) basato sulla tecnologia SNaPshot (Applied Biosystems), indicato di seguito anche come saggio CF-SNAP+20. Il saggio CF-SNAP+20 è stato ideato dagli autori dell’invenzione per indagare 20 mutazioni mediante amplificazione PCR di 7 esoni del gene CFTR, successivo minisequencing e analisi mediante elettroforesi capillare. Queste mutazioni si sono rivelate particolarmente frequenti nell’Italia Centrale, ma ben rappresentate anche nel resto d’Italia e in Europa. Il saggio CF-SNAP+20 è stato ideato per essere il complemento di un test commerciale noto (PCR/OLA/SCS: indagine delle 31 mutazioni del gene CFTR più frequenti nel mondo, Celera Diagnostics), anche nella versione aggiornata CF-OLA (indagine delle medesime 31 mutazioni + ulteriori 2, Abbott). Gli autori hanno individuato e selezionato particolari primers di PCR e di minisequencing, hanno messo a punto l’architettura complessiva del saggio (formato a 96-well e reazioni multiplex sia di PCR che di minisequencing), e hanno personalizzato la programmazione del software di analisi con la produzione di un insieme di regole volte ad identificare in maniera automatica le mutazioni eventualmente presenti nel campione.
L’uso della stessa piattaforma strumentale ABI PRISM del test commerciale CF-OLA, dello stesso polimero e la complementarietà delle mutazioni incluse, rendono il saggio CF-SNAP+20 particolarmente interessante per quei laboratori che già utilizzano il test commerciale CF-OLA e in ogni caso per aumentare la sensibilità diagnostica dell’indagine mutazionale del CFTR
Alcohol addiction: a molecular biology perspective.
Full text linkAlcohol misuse represents worldwide an important risk factor for death and disability. Excessive alcohol consumption is widely diffused in different ethnicities and alcohol use is part of the lifestyle of both young and old people. The genetic basis of alcohol dependence concerning ethanol metabolism and the pathways of reward circuits are well known. The role of genetic variants in the neurobiology of addiction as well as in response to medication in alcoholism therapy still represents an intriguing argument that needs to be deeply analyzed and explained. The molecular approach to the study of these aspects could be difficult because of the large number of genes and variations involved. Our work is intended to offer an overview of genes and variants involved in alcohol addiction and pharmacogenetics. Our aim is to delineate a molecular approach strategy to look at alcohol dependence from a genetic and applicative point of view. The indications provided in this work should be of help for those who wish to undertake a molecular study of this multifactorial disease
A reassessment of semiquantitative analytical procedures for DNA methylation: Comparison of bisulfite- and HpaII polymerase-chain-reaction-based methods
No full textTwo techniques in particular are used to study site-specific DNA methylation: genomic sequencing after bisulfite modification and polymerase chain reaction after digestion by a methylation-sensitive endonuclease (usually HpaII). Only the former methodology assesses the methylation status of all the cytosine residues in the DNA sequence, but it is so complex and time consuming that the latter procedure, though limited to the restriction sites recognized by the endonucleasets) used, is often preferred at least for a first analysis. In this work we investigate differences between these two techniques in the assessment of DNA methylation and offer some suggestions on how to avoid uncorrected results. Although there is substantial accordance in the results obtained using these different techniques, we observed a general overestimate for methylation levels above 30% and a general underestimate for methylation levels below this value using the HpaII/ PCR technique in the study of methylation of the 5'-flanking region of the mouse myogenin gene in cultured muscle cells and mouse tissues. (c) 2005 Elsevier Inc. All rights reserved
Erythroid differentiation and regulatory gene expression are modulated by adenosine derivatives interfering with S-adenosylmethionine metabolic pathway
No full textThe differentiation of murine erythroleukemia cells and the expression of SCL, Id1 and c-myc regulatory genes were studied. The first gene is a positive regulator of differentiation, while the other two are both negative regulators of differentiation and positive regulators of proliferation. Accordingly, our data show that when differentiation is stimulated SCL is upregulated while Id1 and c-myc are, coordinately, downregulated. The cultures were treated with two adenosine derivatives, 3-deazaadenosine and 3-deazaaristeromycin, known to act on the metabolic pathway of the methyl donor S-adenosylmethionin, in order to assess the possibility of a coordinated modulation, by these drugs, of regulatory gene expression and erythroid cell differentiation. 3-Deazaaristeromycin caused the simultaneous downregulation of Id1 and c-myc, whereas 3-deazaadenosine caused their upregulation; both drugs produced a transient increase in SCL expression. The use of these drugs evidenced a predominant regulatory effect of negative regulators in the control of erythroid differentiation. The distinct effects of the two drugs on regulatory gene expression led to an increased differentiation induced by 3-deazaaristeromycin and to a reduced differentiation induced by 3-deazaadenosine, if compared with controls. Southern analysis of DNA digested with methylation-specific restriction endonucleases showed that the administration of 3-deazaaristeromycin resulted in hypomethylation of SCL and c-myc, thus evidencing, in these cells, a clear correlation between DNA hypomethylation and differentiation but no straightforward correlation between DNA methylation and gene expression
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