Search results for "Genome"
showing 10 items of 1913 documents
Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans.
2006
By combining all the data available from the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) project, we have been able to identify 17 microsatellite markers showing consistent evidence for apparent association. As might be expected five of these markers map within the Major Histocompatibility Complex (MHC) and are in LD with HLA-DRB1. Individual genotyping of the 12 non-MHC markers confirmed association for three of them — D11S1986, D19S552 and D20S894. Association mapping across the candidate genes implicated by these markers in 937 UK trio families revealed modestly associated haplotypes in JAG1 (p=0.019) on chromosome 20p12.2 and POU2AF1 (p=0.003) on chromosome 11q23.1.
A New Combinatorial Approach to Sequence Comparison
2008
In this paper we introduce a new alignment-free method for comparing sequences which is combinatorial by nature and does not use any compressor nor any information-theoretic notion. Such a method is based on an extension of the Burrows-Wheeler Transform, a transformation widely used in the context of Data Compression. The new extended transformation takes as input a multiset of sequences and produces as output a string obtained by a suitable rearrangement of the characters of all the input sequences. By using such a transformation we give a general method for comparing sequences that takes into account how much the characters coming from the different input sequences are mixed in the output…
The Putative Natural Killer Decoy Early Genem04(gp34) of Murine Cytomegalovirus Encodes an Antigenic Peptide Recognized by Protective Antiviral CD8 T…
2000
ABSTRACTSeveral early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation to cytolytic T lymphocytes (CTL). Specifically, them152gene product gp37/40 causes retention of MHC-I molecules in the endoplasmic reticulum (ER)-Golgi intermediate compartment. Lack of MHC-I on the cell surface should activate natural killer (NK) cells recognizing the “missing self.” The retention, however, is counteracted by them04early gene product gp34, which binds to folded MHC-I molecules in the ER and directs the complex to the cell surface. It was thus speculated that gp34 mi…
The Immune Evasion Paradox: Immunoevasins of Murine Cytomegalovirus Enhance Priming of CD8 T Cells by Preventing Negative Feedback Regulation▿
2008
ABSTRACTCytomegaloviruses express glycoproteins that interfere with antigen presentation to CD8 T cells. Although the molecular modes of action of these “immunoevasins” differ between cytomegalovirus species, the convergent biological outcome is an inhibition of the recognition of infected cells. In murine cytomegalovirus, m152/gp40 retains peptide-loaded major histocompatibility complex class I molecules in acis-Golgi compartment, m06/gp48 mediates their vesicular sorting for lysosomal degradation, and m04/gp34, although not an immunoevasin in its own right, appears to assist in the concerted action of all three molecules. Using the Ld-restricted IE1 epitope YPHFMPTNL in the BALB/c mouse m…
Distribution of Fitness Effects Caused by Single-Nucleotide Substitutions in Bacteriophage f1
2010
Empirical knowledge of the fitness effects of mutations is important for understanding many evolutionary processes, yet this knowledge is often hampered by several sources of measurement error and bias. Most of these problems can be solved using site-directed mutagenesis to engineer single mutations, an approach particularly suited for viruses due to their small genomes. Here, we used this technique to measure the fitness effect of 100 single-nucleotide substitutions in the bacteriophage f1, a filamentous single-strand DNA virus. We found that approximately one-fifth of all mutations are lethal. Viable ones reduced fitness by 11% on average and were accurately described by a log-normal dist…
Viral Mutation Rates
2010
Accurate estimates of virus mutation rates are important to understand the evolution of the viruses and to combat them. However, methods of estimation are varied and often complex. Here, we critically review over 40 original studies and establish criteria to facilitate comparative analyses. The mutation rates of 23 viruses are presented as substitutions per nucleotide per cell infection (s/n/c) and corrected for selection bias where necessary, using a new statistical method. The resulting rates range from 108 to106 s/n/c for DNA viruses and from 106 to 104 s/n/c for RNA viruses. Similar to what has been shown previously for DNA viruses, there appears to be a negative correlation between mut…
Extremely high mutation rate of a hammerhead viroid
2009
Supporting information (Materials and methods, figs. S1-S3, suppl. references) available at: http://www.sciencemag.org/cgi/data/323/5919/1308/DC1/1
Correlation between mutation rate and genome size in riboviruses: mutation rate of bacteriophage Qβ.
2013
Abstract Genome sizes and mutation rates covary across all domains of life. In unicellular organisms and DNA viruses, they show an inverse relationship known as Drake’s rule. However, it is still unclear whether a similar relationship exists between genome sizes and mutation rates in RNA genomes. Coronaviruses, the RNA viruses with the largest genomes (∼30 kb), encode a proofreading 3′ exonuclease that allows them to increase replication fidelity. However, it is unknown whether, conversely, the RNA viruses with the smallest genomes tend to show particularly high mutation rates. To test this, we measured the mutation rate of bacteriophage Qβ, a 4.2-kb levivirus. Amber reversion-based Luria–D…
Variability in the mutation rates of RNA viruses
2014
ABSTRACT: It is well established that RNA viruses show extremely high mutation rates, but less attention has been paid to the fact that their mutation rates also vary strongly, from 10-6 to 10-4 substitutions per nucleotide per cell infection. The causes explaining this variability are still poorly understood, but candidate factors are the viral genome size and polarity, host-specific gene expression patterns, or the intracellular environment. Differences between animal and plant viruses, or between arthropod-borne and directly transmitted viruses have also been postulated. Finally, RNA viruses may be able to regulate the rate at which new mutations spread in the population by modifying f…
Effect of mismatch repair on the mutation rate of bacteriophage ϕX174
2015
Viral mutation rates vary widely in nature, yet the mechanistic and evolutionary determinants of this variability remain unclear. Small DNA viruses mutate orders of magnitude faster than their hosts despite using host-encoded polymerases for replication, which suggests these viruses may avoid post-replicative repair. Supporting this, the genome of bacteriophage ϕX174 is completely devoid of GATC sequence motifs, which are required for methyl-directed mismatch repair in Escherichia coli . Here, we show that restoration of the randomly expected number of GATC sites leads to an eightfold reduction in the rate of spontaneous mutation of the phage, without severely impairing its replicative capa…