1,720,979 research outputs found
STUDIO DELL’ESOMA MEDIANTE TECNOLOGIE DI GENOTIPIZZAZIONE AD ALTA EFFICIENZA: SEQUENZIAMENTO DI NUOVA GENERAZIONE (NGS) e IBRIDAZIONE GENOMICA COMPARATIVA (CGH), PER L’IDENTIFICAZIONE DI NUOVI GENI MALATTIA IN PATOLOGIE NEUROMUSCOLARI.
No full textOver the years many different approaches and techniques have been employed to get insight genetic data of family and patients. The first approach for genetic studies and gene discovery was the linkage analysis, but to be efficient it required large family or large numbers of patients sharing the same disease phenotype.
The advent of sequencing technology made the genetic analysis more handy but still it was time consuming and not cost effective when a large number of genes needed to be screened , for example in case of diseases with a known genetic heterogeneity as the neuromuscular disorders (NMDs).
The high throughput molecular diagnostics tools such as Comparative Genomic Hybridization (CGH) and next Generation Sequencing (NGS) technology are changing medical genomics by accelerating new disease causing mutations discovery; these techniques could enable quick, reliable and cost-effective analysis of numerous NMD genes in parallel.
The NGS methods promise to speed up the discovery of the genetic causes of diseases both in the research and the clinical setting.
We performed whole exome sequencing analysis (WES) through NGS technology on a family with a Bethlem phenotype (BM) orphan of mutations in COLVI genes and a coohort of patients with a clinical diagnosis of myofibrillar myopathy (MFM).
We performed the linkage analysis on BM family; the linkage regions identified were used as filters in WES output data. We selected four components (two affected and two unaffected) of this family and performed Whole Exome Sequencing by Illumina GAIIe platform obtaining a few candidate genes.
Regarding the MFMs patients, we identified a large rearrangements in laminin alpha 2 (LAMA2) gene through CGH; while WES identified small variations in five patients: mutations in a known gene, and two variations in two novel genes previously unreported as involved in MFMs
Biomarkers in rare neuromuscular diseases
No full textNeuromuscular diseases (NMDs) comprise a range of rare disorders that include both hereditary peripheral neuropathies and myopathies. The heterogeneity and rarity of neuromuscular disorders are challenges for researchers seeking to develop effective diagnosis and treatment strategies. In particular, clinical trials of new therapies are made more difficult due to lack of reliable and monitorable clinical outcome measures. Biomarkers could be a way to speed up research in this field, shedding light on the pathophysiological mechanisms behind such diseases and providing invaluable tools for monitoring their progression, prognosis and response to drug treatment. Furthermore, biomarkers could represent a surrogate endpoint for clinical trials, enabling better stratification of patient cohorts through more accurate diagnosis and prognosis prediction.
This review summarizes the types, applications, characteristics and best strategies for biomarker discovery to date
Rapid, comprehensive analysis of the dystrophin transcript by a custom micro-fluidic exome array
No full textDuchenne and Becker muscular dystrophies are caused by mutations in the dystrophin gene. Both the enormous size of this gene and heterogeneous set of causative mutations behind these pathologies may hamper and even prevent accurate molecular diagnosis. Often RNA analysis is required not only to identify mutations escaping MLPA/CGH or exon sequencing but also to validate the functional effect of novel variations that may affect the exon composition of the DMD gene. We present the design and experimental validation of a new, simple, and easy-to-use platform we call FluiDMD. This platform is based on the Applied Biosystems 7900HT TaqMan ® low-density array technology and is able to define the full-exon composition, profile the dystrophin isoforms present, establish changes in mRNA decay, and potentially identify all deletions/duplications and splicing affecting mutations contemporaneously. Moreover, we demonstrate that this system accurately detects the pathogenic effect of all dystrophin mutations belonging to any category, thereby highlighting the functional validation capacity of this system. The high efficacy and sensitivity of this tool in detecting mutations in the dystrophin transcript can be exploited in a variety of cells/tissues, in particular skin, which is harvested by causing minimum patient discomfort. We therefore propose FluiDMD as a validated diagnostic biomarker for molecular profiling of dystrophinopathies. © 2011 Wiley Periodicals, Inc
Biomarkers in rare diseases
No full textNowadays 7,000 rare diseases (RDs) have been identified with a prevalence less than 5/10,000. Despite of the enormous effort the European Union (EU) has already invested in this field, still 4,000 RDs remain orphan of genetic diagnosis and causative gene identification. The genetic definition of RDs represents a prerequisite for being diagnosed, for having a robust prevention, for entering in a specific standard of care, and ultimately, for being included in clinical trials, often via personalized medicine. It is well established that biomarkers can offer a way to speed up research by understanding the pathophysiological mechanisms of diseases. In particular, biomarkers will offer an invaluable tool for monitoring disease progression, prognosis and response to drug treatment
NMD CHIP: Un Progetto Europeo per la diagnosi delle patologie neuromuscolari
No full textLe malattie neuromuscolari sono un ampio gruppo di patologie ereditarie caratterizzate da eterogeneità genetica e allelica. La
diagnosi molecolare è talora un processo lungo e dispendioso e nel 50% circa dei pazienti non si arriva ad identificare la
mutazione patologica. E’ dunque necessario sviluppare nuove tecniche che permettano ridurre sia tempi e costi delle indagini
sia il numero di pazienti “orfani” di mutazione e dunque privati della possibilità di essere inclusi in trials terapeutici innovativi.
NMD-Chip è un progetto europeo di cui l’Università di Ferrara è partner che ha come scopo quello di studiare i pazienti con
malattie neuromuscolari mediante specifici arrays genomici. Nell’ambito del progetto è stato creato ad oggi un array con 50
geni noti causare malattie neuromuscolari e uno con 40 geni noti causare neuropatie ereditarie. Abbiamo validato l’array per le
malattie neuromuscolari con DNA di pazienti affetti da distrofia di Duchenne identificando la mutazione patologica; abbiamo
inoltre studiato un gruppo di pazienti con miopatia miofibrillare risultati negativi alla analisi molecolare.Il progetto NMD Chip
prevede inoltre che i pazienti risultati negativi per i geni noti vengano studiati con array specifici per geni candidati. Inoltre lo
step finale è lo sviluppo di arrays per la identificazione di piccole mutazioni in tutti i geni indagati. La sensibilità e specificità
diagnostica di questo approccio nei pazienti sarà del 98% e permetterà di ridurre i tempi e i costi delle indagini nelle patologie
neuromuscolari
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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