Search results for "mutation."
showing 10 items of 2808 documents
Effectiveness of screening for known mutations in Sicilian patients with "probable" familial hypercholesterolemia.
2002
Background and Aim: More than 750 mutations in the low-density lipoprotein (LDL) receptor gene are currently known to cause familial hypercholesterolemia (FH), but the array of mutations varies considerably in different populations. The definition of essentially all the LDL receptor gene mutations in a population is therefore a prerequisite for the implementation of nation-wide genetic testing for FH. Methods and Results: In this study, a screening strategy based on PCR-enzymatic digestion and PCR-allele specific hybridisation procedures was used to evaluate the frequency distributions of 11 known mutations in a cohort of 214 unrelated subjects meeting the diagnostic criteria of "probable" …
Comparison of two polygenic risk score to identify non-monogenic primary hypocholesterolemias in a large cohort of Italian hypocholesterolemic subjec…
2022
Background: Primary Hypobetalipoproteinemias (HBL) are a group of dominant and recessive monogenic genetic disorders caused by mutations in APOB, PCSK9, ANGPTL3, MTTP, Sar1b genes and characterized by plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5th percentile of the distribution in a given population. Mutations in the candidate genes account only for a small proportion of subjects with HBL suggesting a role for a polygenic contribution to the low cholesterol phenotype. Objective: To explore the complex genetic architecture of HBL we compared two polygenic risk scores in order to assess the role of the polygenic b…
CRISPR-Cas12a-Based Detection of SARS-CoV-2 Harboring the E484K Mutation
2021
The novel respiratory virus SARS-CoV-2 is rapidly evolving across the world with the potential of increasing its transmission and the induced disease. Here, we applied the CRISPR-Cas12a system to detect, without the need of sequencing, SARS-CoV-2 genomes harboring the E484K mutation, first identified in the Beta variant and catalogued as an escape mutation. The E484K mutation creates a canonical protospacer adjacent motif for Cas12a recognition in the resulting DNA amplicon, which was exploited to obtain a differential readout. We analyzed a series of fecal samples from hospitalized patients in Valencia (Spain), finding one infection with SARS-CoV-2 harboring the E484K mutation, which was t…
Permutation Tests in Linear Regression
2015
Exact permutation tests are available only in rather simple linear models. The problem is that, although standard assumptions allow permuting the errors of the model, we cannot permute them in practice, because they are unobservable. Nevertheless, the residuals of the model can be permuted. A proof is given here which shows that it is possible to approximate the unobservable permutation distribution where the true errors are permuted by permuting the residuals. It is shown that approximation holds asymptotically and almost surely for certain quadratic statistics as well as for statistics which are expressible as the maximum of appropriate linear functions. The result is applied to testing t…
Genetic diversity within the R408W phenylketonuria mutation lineages in Europe
2003
The R408W phenylketonuria mutation in Europe has arisen by recurrent mutation in the human phenylalanine hydroxylase (PAH) locus and is associated with two major PAH haplotypes. R408W-2.3 exhibits a west-to-east cline of relative frequency reaching its maximum in the Balto–Slavic region, while R408W-1.8 exhibits an east-to-west cline peaking in Connacht, the most westerly province of Ireland. Spatial autocorrelation analysis has demonstrated that the R408W-2.3 cline, like that of R408W-1.8, is consistent with a pattern likely to have been established by human dispersal. Genetic diversity within wild-type and R408W chromosomes in Europe was assessed through variable number tandem repeat (VNT…
Contribution of Taq polymerase-induced errors to the estimation of RNA virus diversity.
1998
The genetic diversity of a vesicular stomatitis virus population was analysed by RT-PCR, cloning and sequencing of two approximately 500 nucleotide regions of the virus genome. PCR amplifications were performed in parallel experiments with both Taq and Pfu DNA polymerases, and important differences were observed. Between 10 and 22 mutations were detected when virus populations were analysed by Taq amplification (20 clones from each region), whereas amplification of the same samples with Pfu revealed between 0 and 5 mutations. PCR fidelity assays, performed under the same PCR conditions as those used in the population analysis, showed that the Taq error-rate estimate of 0.27 x 10(-4) misinco…
Fitness Trade-Offs Determine the Role of the Molecular Chaperonin GroEL in Buffering Mutations
2015
Molecular chaperones fold many proteins and their mutated versions in a cell and can sometimes buffer the phenotypic effect of mutations that affect protein folding. Unanswered questions about this buffering include the nature of its mechanism, its influence on the genetic variation of a population, the fitness trade-offs constraining this mechanism, and its role in expediting evolution. Answering these questions is fundamental to understand the contribution of buffering to increase genetic variation and ecological diversification. Here, we performed experimental evolution, genome resequencing, and computational analyses to determine the trade-offs and evolutionary trajectories of Escherich…
The transcriptome of Spodoptera exigua larvae exposed to different types of microbes.
2012
We have obtained and characterized the transcriptome of Spodoptera exigua larvae with special emphasis on pathogen-induced genes. In order to obtain a highly representative transcriptome, we have pooled RNA from diverse insect colonies, conditions and tissues. Sequenced cDNA included samples from 3 geographically different colonies. Enrichment of RNA from pathogen-related genes was accomplished by exposing larvae to different pathogenic and non-pathogenic microbial agents such as the bacteria Bacillus thuringiensis, Micrococcus luteus, and Escherichia coli, the yeast Saccharomyces cerevisiae, and the S. exigua nucleopolyhedrovirus (SeMNPV). In addition, to avoid the loss of tissue-specific …
The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus.
2004
6 pages, 3 figures.-- PMID: 15159545 [PubMed].-- PMCID: PMC420405.-- Supporting information (Table 3: Relevant information about each single-nucleotide substation mutant created) available at: http://www.pnas.org/content/101/22/8396/suppl/DC1
The population genetics and evolutionary epidemiology of RNA viruses.
2004
Key Points The authors discuss the main mechanisms of RNA virus evolution — mutation, recombination, natural selection, genetic drift and migration, and how these interact to shape the genetic structure of populations.The quasispecies model of RNA virus evolution is explained and the question of whether this model provides an accurate description of RNA virus evolution is discussed.Experiments that can be carried out to test the basic principles of evolutionary theory are briefly described. The authors review what such experiments have told us about virus evolution and, more widely, what these experiments have revealed in terms of general evolutionary principles.RNA viruses evolve quickly, …