Search results for "VARIATION"
showing 10 items of 2124 documents
RNAi knock-down mice: an emerging technology for post-genomic functional genetics
2003
RNA interference (RNAi) has been extensively used for sequence-specific silencing of gene function in mammalian cells. The latest major breakthrough in the application of RNAi technology came from experiments demonstrating RNAi-mediated gene repression in mice and rats. After more than two decades of functional mouse research aimed at developing and continuously improving transgenic and knock-out technology, the advent of RNAi knock-down mice represents a valuable new alternative for studying gene function in vivo. In this review we provide some basic insight as to how RNAi can induce gene silencing to then focus on recent findings concerning the applicability of RNAi for regulating gene fu…
Genetic variability in the endemic Leucojum valentinum
2009
The genetic variability of Leucojum valentinum Pau (Amaryllidaceae), a vulnerable endemic species restricted to a small area in the region of Valencia (Eastern Spain), has been studied using random amplified polymorphic DNA (RAPD) markers. A total of 197 individuals from eleven populations were studied using 13 RAPD primers. Our results show high variability for the species, low differentiation among populations and uncorrelated levels of genetic variability and population size. Four groups in which three populations (SAG, PUG and COL) are separated from all the others were found, but without connection to geographical location.
Class II HLA interactions modulate genetic risk for multiple sclerosis
2015
Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and cla…
Genetic Variability of Hepatitis C Virus before and after Combined Therapy of Interferon plus Ribavirin
2008
We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, t…
Phylogenomic Analysis Reveals Deep Divergence and Recombination in an Economically Important Grapevine Virus
2015
The evolutionary history of the exclusively grapevine (Vitis spp.) infecting, grapevine leafroll-associated virus 3 (GLRaV-3) has not been studied extensively, partly due to limited available sequence data. In this study we trace the evolutionary history of GLRaV-3, focussing on isolate GH24, a newly discovered variant. GH24 was discovered through the use of next-generation sequencing (NGS) and the whole genome sequence determined and validated with Sanger sequencing. We assembled an alignment of all 13 available whole genomes of GLRaV-3 isolates and all other publicly available GLRaV-3 sequence data. Using multiple recombination detection methods we identified a clear signal for recombinat…
TCR Clonality and Genomic Instability Signatures as Prognostic Biomarkers in High Grade Serous Ovarian Cancer.
2021
Simple Summary High-grade serous ovarian carcinoma (HGSC) could be analyzed with a molecular stratification defined by different genomic instability signatures associated with specific mutational process and prognostic biomarkers. Immune infiltrate is known to be a robust biomarker in HGSC. We aimed to investigate immune parameters according to genomic instability signatures. We observed that homologous recombination deficiency positive, copy cumber variant signature 7 and TCR (T cells receptor) clonality are good prognostic biomarkers in HGSC. Combining TCR clonality and genomic instability signature or T cell infiltration improved the prognostic value compared to each variable taken alone…
Genomic instability in an interspecific hybrid of the genus Saccharomyces: a matter of adaptability
2020
Ancient events of polyploidy have been linked to huge evolutionary leaps in the tree of life, while increasing evidence shows that newly established polyploids have adaptive advantages in certain stress conditions compared to their relatives with a lower ploidy. The genus Saccharomyces is a good model for studying such events, as it contains an ancient whole-genome duplication event and many sequenced Saccharomyces cerevisiae are, evolutionary speaking, newly formed polyploids. Many polyploids have unstable genomes and go through large genome erosions; however, it is still unknown what mechanisms govern this reduction. Here, we sequenced and studied the natural S. cerevisiae × Saccharomyces…
Variations in Substitution Rate in Human and Mouse Genomes
2003
We present a method to quantify spatial fluctuations of the substitution rate on different length scales throughout genomes of eukaryotes. The fluctuations on large length scales are found to be predominantly a consequence of a coarse-graining effect of fluctuations on shorter length scales. This is verified for both the mouse and the human genome. We also found that both species show similar standard deviation of fluctuations even though their mean substitution rate differs by a factor of two. Our method furthermore allows to determine time-resolved substitution rate maps from which we can compute auto-correlation functions in order to quantify how fast the spatial fluctuations in substitu…
Identification of sapovirus infection among Japanese infants in a day care center.
2005
A total of 921 fecal specimens collected from 44 infants in a day care center in Tokyo, Japan during June 1999 to July 2000 were tested for the presence of sapovirus by reverse transcription-polymerase chain reaction (RT-PCR). Of 88 fecal specimens from infants with acute gastroenteritis, 2.3% (2) were found to be positive for sapovirus. Twenty-two of 833 (2.6%) fecal specimens collected from asymptomatic infants were also infected with this virus. Another interesting feature was the demonstration of high incidence of sapovirus infection (95.5%, 21 of 22) identified in a single day care center, which was not due to viral shedding after the latest acute gastroenteritis. Sapovirus was subject…
Genotype and Allele Frequencies of Drug-Metabolizing Enzymes and Drug Transporter Genes Affecting Immunosuppressants in the Spanish White Population
2013
Interpatient variability in drug response can be widely explained by genetically determined differences in metabolizing enzymes, drug transporters, and drug targets, leading to different pharmacokinetic and/or pharmacodynamic behaviors of drugs. Genetic variations affect or do not affect drug responses depending on their influence on protein activity and the relevance of such proteins in the pathway of the drug. Also, the frequency of such genetic variations differs among populations, so the clinical relevance of a specific variation is not the same in all of them. In this study, a panel of 33 single nucleotide polymorphisms in 14 different genes (ABCB1, ABCC2, ABCG2, CYP2B6, CYP2C19, CYP2C…