Search results for "Mutational analysis"
showing 10 items of 245 documents
Preservation of genetic and regulatory robustness in ancient gene duplicates of Saccharomyces cerevisiae
2014
[EN] Biological systems remain robust against certain genetic and environmental challenges. Robustness allows the exploration of ecological adaptations. It is unclear what factors contribute to increasing robustness. Gene duplication has been considered to increase genetic robustness through functional redundancy, accelerating the evolution of novel functions. However, recent findings have questioned the link between duplication and robustness. In particular, it remains elusive whether ancient duplicates still bear potential for innovation through preserved redundancy and robustness. Here we have investigated this question by evolving the yeast Saccharomyces cerevisiae for 2200 generations …
Mechanisms of quinolone resistance in Aeromonas species isolated from humans, water and eels.
2009
Mechanisms of resistance were determined in 33 quinolone-resistant isolates of the species Aeromonas hydrophila, Aeromonas caviae, Aeromonas media, Aeromonas salmonicida, Aeromonas popoffii and Aeromonas veronii, recovered from humans, freshwater and eels. The quinolone resistance-determining regions (QRDRs) of gyrA and parC genes were sequenced in these resistant strains, as well as in 8 quinolone-sensitive Aeromonas used as controls. All quinolone-resistant Aeromonas carried point mutations in the gyrA QRDR at codon 83, respectively giving rise to substitutions Ser(83)-->Ile (32 strains) or Ser(83)-->Val (1 strain). Almost half of these isolates (48%) carried additional point mutations in…
Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis
2006
Familial haemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous disorder characterised by constitutive defects in cellular cytotoxicity resulting in fever, hepatosplenomegaly and cytopenia, and the outcome is fatal unless treated by chemoimmunotherapy followed by haematopoietic stem‐cell transplantation. Since 1999, mutations in the perforin gene giving rise to this disease have been identified; however, these account only for 40% of cases. Lack of a genetic marker hampers the diagnosis, suitability for transplantation, selection of familial donors, identification of carriers, genetic counselling and prenatal diagnosis. Mutations in the Munc13–4 gene have recently been des…
A familial disorder of altered DNA-methylation
2014
BackgroundIn a subset of imprinting disorders caused by epimutations, multiple imprinted loci are affected. Familial occurrence of multilocus imprinting disorders is rare.Purpose/objectiveWe have investigated the clinical and molecular features of a familial DNA-methylation disorder.MethodsTissues of affected individuals and blood samples of family members were investigated by conventional and molecular karyotyping. Sanger sequencing and RT-PCR of imprinting-associated genes (NLRP2, NLRP7, ZFP57, KHDC3L, DNMT1o), exome sequencing and locus-specific, array-based and genome-wide technologies to determine DNA-methylation were performed.ResultsIn three offspring of a healthy couple, we observed…
Extensive molecular analysis of patients bearing CFTR-related disorders.
2012
Cystic fibrosis transmembrane conductance regulator (CFTR)–related disorders (CFTR-RDs) may present with pancreatic sufficiency, normal sweat test results, and better outcome. The detection rate of mutations is lower in CFTR-RD than in classic CF: mutations may be located in genes encoding proteins that interact with CFTR or support channel activity. We tested the whole CFTR coding regions in 99 CFTR-RD patients, looking for gene mutations in solute carrier (SLC) 26A and in epithelial Na channel (ENaC) in 33 patients who had unidentified mutations. CFTR analysis revealed 28 mutations, some of which are rare. Of these mutations, RT-PCR demonstrated that the novel 1525-1delG impairs exon 10 s…
The Epithelial Mesenchymal Transition Process in Wilms Tumor
2011
Background Until now, only a few mouse-transplanted human tumors or experimental Wilms tumor (WT) cell lines have been described. The aim of this study was to show the biological behavior, including histology, immunohistochemistry (IHC), and molecular biology, of a WT including the original tumor and metastasis transferred into nude mice and followed for successive generations in xenografts. Methods A WT metastasis was xenotransplanted into nude mice and the mice was monitored for 7 passages over a period of 29 months; the original neoplasm was comparatively studied. The morphology was evaluated by optical and electron microscopy. The protein expression was analyzed by immunohistochemistry …
Prevalence of Angelman syndrome and Prader-Willi syndrome in Estonian children: sister syndromes not equally represented.
2006
In 2000-2004, we performed a focused search for individuals with Angelman syndrome (AS) and Prader-Willi syndrome (PWS) aiming to establish the prevalence data for the individuals born between 1984 and 2004 in Estonia. All persons with probable AS or PWS (n = 184) were studied using the DNA methylation test. Individuals with abnormal methylation were all further tested by chromosomal and FISH analysis, and if necessary for uniparental disomy and UBE3A gene mutation. Nineteen cases with abnormal methylation test result were identified. Seven of them had AS, including six (85.7%) due to 15q11-13 deletion and one paternal UPD15. Twelve subjects had PWS: 4 (33%) 15q11-13 deletions, 6 (50%) mate…
Confidence-based Somatic Mutation Evaluation and Prioritization
2012
Next generation sequencing (NGS) has enabled high throughput discovery of somatic mutations. Detection depends on experimental design, lab platforms, parameters and analysis algorithms. However, NGS-based somatic mutation detection is prone to erroneous calls, with reported validation rates near 54% and congruence between algorithms less than 50%. Here, we developed an algorithm to assign a single statistic, a false discovery rate (FDR), to each somatic mutation identified by NGS. This FDR confidence value accurately discriminates true mutations from erroneous calls. Using sequencing data generated from triplicate exome profiling of C57BL/6 mice and B16-F10 melanoma cells, we used the exist…
The FBN2 gene: new mutations, locus-specific database (Universal Mutation Database FBN2), and genotype-phenotype correlations.
2009
International audience; Congenital contractural arachnodactyly (CCA) is an extremely rare disease, due to mutations in the FBN2 gene encoding fibrillin-2. Another member of the fibrillin family, the FBN1 gene, is involved in a broad phenotypic continuum of connective-tissue disorders including Marfan syndrome. Identifying not only what is in common but also what differentiates these two proteins should enable us to better comprehend their respective functions and better understand the multitude of diseases in which these two genes are involved. In 1995 we created a locus-specific database (LSDB) for FBN1 mutations with the Universal Mutation Database (UMD) tool. To facilitate comparison of …
RNA sequencing-based transcriptome profiling of cardiac tissue Implicados novela putative disease mechanisms in FLNC-associated arrhythmogenic cardio…
2020
Arrhythmogenic cardiomyopathy (ACM) encompasses a group of inherited cardiomyopathies including arrhythmogenic right ventricular cardiomyopathy (ARVC) whose molecular disease mechanism is associated with dysregulation of the canonical WNT signalling pathway. Recent evidence indicates that ARVC and ACM caused by pathogenic variants in the FLNC gene encoding filamin C, a major cardiac structural protein, may have different molecular mechanisms of pathogenesis. We sought to identify dysregulated biological pathways in FLNC-associated ACM. RNA was extracted from seven paraffin-embedded left ventricular tissue samples from deceased ACM patients carrying FLNC variants and sequenced. Transcript le…