Search results for "VARIATION"
showing 10 items of 2124 documents
Molecular epidemiology of KPC-producing Klebsiella pneumoniae from invasive infections in Italy: Increasing diversity with predominance of the ST512 …
2016
Objectives The spread of carbapenem-resistant Enterobacteriaceae (CRE) represents one of the most worrisome problems for clinical medicine worldwide. In Italy, the Antibiotic-Resistance-Istituto Superiore di Sanita surveillance network, in collaboration with the Committee for Antimicrobial Agents of the Italian Society of Clinical Microbiologists, promoted a study to investigate the carbapenem-resistance mechanisms, clonal relatedness and capsular typing of a recent collection of carbapenem-resistant Klebsiella pneumoniae (CR-KP). Methods A total of 17 laboratories distributed across Italy collected all consecutive non-replicate CR-KP isolated from invasive infections during two different s…
Genetic Polymorphism in Wine Yeasts: Mechanisms and Methods for Its Detection
2017
The processes of yeast selection for using as wine fermentation starters have revealed a great phenotypic diversity both at interspecific and intraspecific level, which is explained by a corresponding genetic variation among different yeast isolates. Thus, the mechanisms involved in promoting these genetic changes are the main engine generating yeast biodiversity. Currently, an important task to understand biodiversity, population structure and evolutionary history of wine yeasts is the study of the molecular mechanisms involved in yeast adaptation to wine fermentation, and on remodeling the genomic features of wine yeast, unconsciously selected since the advent of winemaking. Moreover, the…
Collective Infectious Units in Viruses
2017
Increasing evidence indicates that viruses do not simply propagate as independent virions among cells, organs, and hosts. Instead, viral spread is often mediated by structures that simultaneously transport groups of viral genomes, such as polyploid virions, aggregates of virions, virion-containing proteinaceous structures, secreted lipid vesicles, and virus-induced cell-cell contacts. These structures increase the multiplicity of infection, independently of viral population density and transmission bottlenecks. Collective infectious units may contribute to the maintenance of viral genetic diversity, and could have implications for the evolution of social-like virus-virus interactions. These…
Ancient European dog genomes reveal continuity since the Early Neolithic
2017
Europe has played a major role in dog evolution, harbouring the oldest uncontested Palaeolithic remains and having been the centre of modern dog breed creation. Here we sequence the genomes of an Early and End Neolithic dog from Germany, including a sample associated with an early European farming community. Both dogs demonstrate continuity with each other and predominantly share ancestry with modern European dogs, contradicting a previously suggested Late Neolithic population replacement. We find no genetic evidence to support the recent hypothesis proposing dual origins of dog domestication. By calibrating the mutation rate using our oldest dog, we narrow the timing of dog domestication t…
Assessing Human Genetic Variations in Glucose Transporter SLC2A10 and Their Role in Altering Structural and Functional Properties
2018
Purpose: Demand is increasing for clinical genomic sequencing to provide diagnoses for patients presenting phenotypes indicative of genetic diseases, but for whom routine genetic testing failed to yield a diagnosis. DNA-based testing using high-throughput technologies often identifies variants with insufficient evidence to determine whether they are disease-causal or benign, leading to categorization as variants of uncertain significance (VUS). Methods: We used molecular modeling and simulation to generate specific hypotheses for the molecular effects of variants in the human glucose transporter, GLUT10 (SLC2A10). Similar to many disease-relevant membrane proteins, no experimentally derived…
A multicentric study to evaluate the use of relative retention times in targeted proteomics.
2016
Despite the maturity reached by targeted proteomic strategies, reliable and standardized protocols are urgently needed to enhance reproducibility among different laboratories and analytical platforms, facilitating a more widespread use in biomedical research. To achieve this goal, the use of dimensionless relative retention times (iRT), defined on the basis of peptide standard retention times (RT), has lately emerged as a powerful tool. The robustness, reproducibility and utility of this strategy were examined for the first time in a multicentric setting, involving 28 laboratories that included 24 of the Spanish network of proteomics laboratories (ProteoRed-ISCIII). According to the results…
Genetically elevated gamma-glutamyltransferase and Alzheimer's disease
2018
Observational epidemiological evidence supports a linear and independent association between serum gamma-glutamyltransferase (GGT) concentrations and the risk of Alzheimer's disease (AD). However, the causality of this association has not been previously investigated. We sought to assess the causal nature of this association using a Mendelian randomization (MR) approach. Using inverse-variance weighted MR analysis, we assessed the association between GGT and AD using summary statistics for single nucleotide polymorphism (SNP)-AD associations obtained from the International Genomics of Alzheimer's Project of 17,008 individuals with AD and 37,154 controls. We used 26 SNPs significantly associ…
Recommendations for the implementation of BRCA testing in the care and treatment pathways of ovarian cancer patients
2016
In the last 20 years, following the identification of the BRCA1 and BRCA2 genes (hereinafter referred to as the BRCA genes), preventive pathways have been developed for the identification and clinical management of individuals at high risk of developing breast and ovarian cancer due to the presence of a pathogenic variant in either of these genes. These pathways are aimed at educating high-risk subjects on programs targeted toward early diagnosis and cancer risk reduction. The approval of a novel class of drugs, the PARP enzyme inhibitors, for the treatment of ovarian cancer patients carrying high-risk BRCA pathogenic variants has changed this scenario. BRCA testing, in addition to providin…
Genomic Amplifications and Distal 6q Loss: Novel Markers for Poor Survival in High-risk Neuroblastoma Patients.
2018
Abstract Background Neuroblastoma is characterized by substantial clinical heterogeneity. Despite intensive treatment, the survival rates of high-risk neuroblastoma patients are still disappointingly low. Somatic chromosomal copy number aberrations have been shown to be associated with patient outcome, particularly in low- and intermediate-risk neuroblastoma patients. To improve outcome prediction in high-risk neuroblastoma, we aimed to design a prognostic classification method based on copy number aberrations. Methods In an international collaboration, normalized high-resolution DNA copy number data (arrayCGH and SNP arrays) from 556 high-risk neuroblastomas obtained at diagnosis were coll…
Copy number variations inDCC/18q andERBB2/17q are associated with disease-free survival in microsatellite stable colon cancer
2017
We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q, and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% stage II patients vs 31% stage III patients (p<0.0001). The 4-year DFS was significan…