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At least 361 records · Page 20Linked to original sources
PubMed1994

Mitochondrial control region and protein coding genes sequence variation among phenotypic forms of brown trout Salmo trutta from northern Italy.

The Pô River basin of northern Italy is the home of distinctive and endemic morphological forms of brown trout Salmo trutta. We used PCR-direct sequencing and RFLP techniques to study variation in the mitochondrial control region of 225 trout in order to assess genetic relatedness among 18 populations from that region. The distribution analysis of these genotypes among north Italian populations confirmed the phylogenetic differentiation of marbled trout Salmo trutta marmoratus populations and the postglacial origin of S. t. carpio. Extensive genetic heterogeneity was observed among morphologically identical S. t. fario populations. Introgression with domestic strains of Atlantic basin origin was detected in all forms. In order to assess the phylogenetic congruence detected in coding and noncoding regions of the mitochondrial genome, we also analysed sequence variation in segments of the cytochrome b and ATPase subunit VI genes among representatives of all variants detected in the analysis of the control region. Variation in protein coding genes was only slightly less than that observed in the control region of the same individuals, both in terms of number of variants detected and of pairwise sequence divergence estimates among variants. Phylogenetic analysis based on protein coding genes sequences identified the same phylogenetic groupings defined by the control region analysis and also allowed a partial resolution of their phyletic relationships that was previously unresolved. However, coding and noncoding segments differed substantially in the transition-transversion ratio (17:0 in coding segments vs. 17:6 in control region segments).

Animals↗
PubMed1999

Genome degradation is an ongoing process in Rickettsia.

To study reductive evolutionary processes in bacterial genomes, we examine sequences in the Rickettsia genomes which are unconstrained by selection and evolve as pseudogenes, one of which is the metK gene, which codes for AdoMet synthetase. Here, we sequenced the metK gene and three surrounding genes in eight different species of the genus Rickettsia. The metK gene was found to contain a high incidence of deletions in six lineages, while the three genes in its surroundings were functionally conserved in all eight lineages. A more drastic example of gene degradation was identified in the metK downstream region, which contained an open reading frame in Rickettsia felis. Remnants of this open reading frame could be reconstructed in five additional species by eliminating sites of frameshift mutations and termination codons. A detailed examination of the two reconstructed genes revealed that deletions strongly predominate over insertions and that there is a strong transition bias for point mutations which is coupled to an excess of GC-to-AT substitutions. Since the molecular evolution of these inactive genes should reflect the rates and patterns of neutral mutations, our results strongly suggest that there is a high spontaneous rate of deletions as well as a strong mutation bias toward AT pairs in the Rickettsia genomes. This may explain the low genomic G + C content (29%), the small genome size (1.1 Mb), and the high noncoding content (24%), as well as the presence of several pseudogenes in the Rickettsia prowazekii genome.

Base Sequence↗
PubMed2007

Predicting tissue-specific enhancers in the human genome.

Determining how transcriptional regulatory signals are encoded in vertebrate genomes is essential for understanding the origins of multicellular complexity; yet the genetic code of vertebrate gene regulation remains poorly understood. In an attempt to elucidate this code, we synergistically combined genome-wide gene-expression profiling, vertebrate genome comparisons, and transcription factor binding-site analysis to define sequence signatures characteristic of candidate tissue-specific enhancers in the human genome. We applied this strategy to microarray-based gene expression profiles from 79 human tissues and identified 7187 candidate enhancers that defined their flanking gene expression, the majority of which were located outside of known promoters. We cross-validated this method for its ability to de novo predict tissue-specific gene expression and confirmed its reliability in 57 of the 79 available human tissues, with an average precision in enhancer recognition ranging from 32% to 63% and a sensitivity of 47%. We used the sequence signatures identified by this approach to successfully assign tissue-specific predictions to approximately 328,000 human-mouse conserved noncoding elements in the human genome. By overlapping these genome-wide predictions with a data set of enhancers validated in vivo, in transgenic mice, we were able to confirm our results with a 28% sensitivity and 50% precision. These results indicate the power of combining complementary genomic data sets as an initial computational foray into a global view of tissue-specific gene regulation in vertebrates.

Animals↗
PubMed1995

The L protein of Rift Valley fever virus can rescue viral ribonucleoproteins and transcribe synthetic genome-like RNA molecules.

Overlapping cDNAs representing the complete L segment of Rift Valley fever virus were assembled, and the L protein was expressed via a recombinant vaccinia virus. The transcriptase activity of the L protein was assayed with two types of templates: natural ribonucleoproteins (RNPs) and artificial genome-like RNAs. RNPs purified in a CsCl gradient did not retain the RNA polymerase function, but the activity was restored when the L cDNA was expressed in mammalian cells via a recombinant vaccinia virus. Indeed, after transfection of transcriptase-depleted RNPs in cells infected with the recombinant vaccinia virus expressing the L protein, the mRNAs coding for the N and NSs proteins and to a lesser extent, those coding for the glycoproteins were synthesized as well as the corresponding proteins. The transcriptase activity of the recombinant L protein was then investigated by using synthetic templates containing the reporter chloramphenicol acetyltransferase gene in the antisense orientation flanked by the 3' and 5' noncoding region of the S genomic segment. Our results indicate that after transfection of the RNA templates, transcription was achieved in cells coexpressing both the L and N proteins. Together, the experiments demonstrate that the two proteins N and L are absolutely required and sufficient to reconstitute the transcriptase activity.

Base Sequence↗
PubMed1979

Evolutionary relationships of the primate papovaviruses: base sequence homology among the genomes of simian virus 40, stump-tailed macaque virus, and SA12 virus.

Physical maps of the genomes of the two newly discovered primate papovaviruses, SA12 and stump-tailed macaque virus (STMV), were generated by restriction endonuclease analysis. The base sequence homologies among the genomes of SA12, stump-tailed macaque virus, and simian virus 40 (SV40) were studied by heteroduplex analysis. Heteroduplexes between SA12 and SV40 DNAs and stump-tailed macaque virus and SV40 DNAs were constructed and mounted for electron microscopy in various amounts of formamide to achieve a range of effective temperatures. At each effective temperature, the regions of duplex DNA in the heteroduplexes were measured and localized on the SV40 physical and functional maps. By analyzing the data from this study and rom our previous study (N. Newell, C. J. Lai, G. Khoury, and T. J. Kelly Jr., J. Virol. 25:193-201, 1978) on the base sequence homology between the genomes of BK virus and SV40, some general conclusions have been drawn concerning the evolutionary relationships among the genomes of the primate papovaviruses. The extent of homology among the viral genomes does not reflect the phylogenetic relationships of their hosts. At comparable effective temperatures Tm - 33 degrees C), the heteroduplexes between the DNAs of BK virus and SV40 contained the largest amount of duplex (about 90%). The heteroduplexes made between SA12 and SV40 DNAs were slightly less homologous, containing about 80% duplex. The heteroduplexes made between SV40 and stump-tailed macaque virus DNAs were only 20% duplex under the same conditions. When the various heteroduplexes were mounted for microscopy at effective temperatures greater than Tm - 33 degrees C, the fraction of the duplex DNA decreased in each case, indicating the existence of considerable base mismatching in the homologous regions. When specific coding or noncoding regions of the viral genomes were compared, the data indicated that the extent of sequence divergence differed markedly from one region to another. In all the heteroduplexes studied, there were two regions, located near the junctions between early and late regions on the SV40 map, which were essentially nonhomologous. All of the heteroduplexes studied showed significantly greater homology in the late region than in early region. Within the late region, the sequences coding for the major capsid polypeptide, VP1, were the most highly conserved.

Base Sequence↗
PubMed2026

Evolutionary constraints and regulatory plasticity shape host specialization in the Magnaporthe oryzae species complex.

Rice blast caused by Magnaporthe oryzae threatens global rice production, and wheat blast emergence highlights the pathogen's capacity for host shifts. Although numerous studies have described M. oryzae genome organization and infection mechanisms, critical questions remain regarding the evolutionary drivers of stable host specialization. Importantly, the blast pathogen comprises a species complex of genetically differentiated, host-adapted lineages rather than single homogeneous species. To address this knowledge gap, we integrate evidence from evolutionary genomics, transcriptomics, and metabolomics to develop the "Constrained Plasticity" framework. We argue that host adaptation arises from three interacting layers: genomic scaffolding (including epigenetic and noncoding RNA regulation), regulatory networks (enabling transcriptional plasticity), and metabolic compatibility (determining physiological success). This systems-level perspective explains the long-term stability of host-adapted lineages and the rare breakdowns resulting in host shifts, such as wheat blast. This framework generates testable predictions for pathogen emergence and provides a roadmap for developing lineage-aware resistance strategies.

Oryza↗
PubMed2006

Conservation of noncoding microsatellites in plants: implication for gene regulation.

BACKGROUND: Microsatellites are extremely common in plant genomes, and in particular, they are significantly enriched in the 5' noncoding regions. Although some 5' noncoding microsatellites involved in gene regulation have been described, the general properties of microsatellites as regulatory elements are still unknown. To address the question of microsatellites associated with regulatory elements, we have analyzed the conserved noncoding microsatellite sequences (CNMSs) in the 5' noncoding regions by inter- and intragenomic phylogenetic footprinting in the Arabidopsis and Brassica genomes. RESULTS: We identified 247 Arabidopsis-Brassica orthologous and 122 Arabidopsis paralogous CNMSs, representing 491 CT/GA and CTT/GAA repeats, which accounted for 10.6% of these types located in the 500-bp regions upstream of coding sequences in the Arabidopsis genome. Among these identified CNMSs, 18 microsatellites show high conservation in the regulatory regions of both orthologous and paralogous genes, and some of them also appear in the corresponding positions of more distant homologs in Arabidopsis, as well as in other plants. A computational scan of CNMSs for known cis-regulatory elements showed that light responsive elements were clustered in the region of CT/GA repeats, as well as salicylic acid responsive elements in the (CTT)n/(GAA)n sequences. Patterns of gene expression revealed that 70-80% of CNMS (CTT)n/(GAA)n associated genes were regulated by salicylic acid, which was consistent with the prediction of regulatory elements in silico. CONCLUSION: Our analyses showed that some noncoding microsatellites were conserved in plants and appeared to be ancient. These CNMSs served as regulatory elements involved in light and salicylic acid responses. Our findings might have implications in the common features of the over-represented microsatellites for gene regulation in plant-specific pathways.

Arabidopsis↗
PubMed1994

Population structure of the Japanese eel, Anguilla japonica.

Mitochondrial DNA (mtDNA) sequences that include (a) a part of the cytochrome b gene, (b) two tRNA genes, and (c) a part of the noncoding D-loop region of 31 Anguilla japonica (Japanese eel) and 1 A. marmorata collected from Taiwan, Japan, and mainland China were determined to evaluate the population structure of Japanese eel. Among 30 genotypes identified from the 31 Japanese eel mtDNAs sequenced, there are 58 variable sites, predominantly clustered at the D-loop region. The phylogenetic tree constructed by the unweighted pair-group method with arithmetic mean shows neither significant genealogical branches nor geographic clusters. Furthermore, the sequence-statistics test reveals little, if any, significant genetic differentiation. These results indicate that the 31 Japanese eels might come from a single population. Analysis of sequence variation in mtDNA by using the relationship between the number of segregating sites and the average number of nucleotide differences under the neutral mutation hypothesis reveals that neutral mutation acts as a major factor influencing the evolutionary divergence of the Japanese eel mitochondrial genome sequenced, especially in the noncoding region.

Animals↗
PubMed2001

Genome Evolution of the Cyanobacterium Nostoc linckia under Sharp Microclimatic Divergence at "Evolution Canyon," Israel.

We describe the genomic DNA diversity and divergence of the cyanobacterium Nostoc linckia from "Evolution Canyon," a microsite consisting of ecologically contrasting slopes, south-facing slope (SFS) and north-facing slope (NFS), at lower Nahal Oren, Mt. Carmel, Israel. The opposing slopes share their limestone lithology but vary greatly in their ecology, primarily because of different levels of solar radiation (which is six times higher on the SFS than on the NFS). The warm and xeric SFS displays a tropical African savanna, whereas the cool and mesic NFS displays a temperate South European Mediterranean live-oak maquis shrub forest. The cyanobacterium Nostoc linckia tested here is a sessile microorganism, growing as a carpet on rock surfaces and constantly exposed to environmental fluctuations of solar radiation, temperature, and desiccation. We demonstrate remarkable interslope and intraslope genetic divergence of the genome (including both coding and noncoding regions) of Nostoc linckia, by using 211 AFLP (amplified fragment length polymorphism) DNA molecular marker loci. Genetic polymorphism of N. linckia subpopulations on the ecologically harsher SFS was significantly (p <0.05) higher (p = 99.53%) than was that of the subpopulations on the climatically milder nfs (p = 85.78%). genetic polymorphism (p) and gene diversity (he) were significantly correlated with variables influencing aridity stress: solar radiation (sr) (rp = 0.956; p = 0.046), temperature (tm) (rp = 0.993; p = 0.0068), and day-night temperature difference (tdd) (rp = 0.975; p = 0.025). as in other tested organisms from "evolution canyon", but even more exceptionally because of its completely sedentary nature, we suggest that the climatically stressed sfs environment is responsible for this marked increase of genetic polymorphism, which is maintained by the combined evolutionary forces of diversifying and balancing selection. This could highlight the importance of ecological stress and selection in evolution and its remarkable effect on the genetic system across the prokaryotic genome.

Journal Article↗
PubMed1997

Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia.

BACKGROUND: Epidemiologic studies have demonstrated strong and consistent associations between the detection of human papillomavirus (HPV) type 16 DNA and the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. However, HPV16 is also the most common type of HPV in the normal population, and only a minority of women with HPV16 infection develop cervical cancer. Studies of genomic heterogeneity in HPV16 have demonstrated the presence of multiple variant forms in all human populations examined to date. It is conceivable that the natural variants of HPV16 in a given population may not have the same biologic behavior. PURPOSE: This study was designed to determine the association between natural variants of HPV16 and the risk of biopsy-confirmed CIN 2 or 3, the most important precancerous lesions of the uterine cervix. METHODS: Prospective studies were conducted among 1) women attending a university and 2) women presenting to a sexually transmitted disease clinic. Subjects were eligible for inclusion in this investigation if the initial cytologic findings did not reveal CIN 2-3 and HPV16 DNA was detected by means of a polymerase chain reaction (PCR)-based method in one or more cervical or vulvovaginal samples. Eligible subjects were followed every 4 months with cervical Pap smears and colposcopic examinations. Women were referred for biopsy if cytology or colposcopy suggested CIN 2-3. Two groups of HPV16 variants, prototype-like and nonprototype-like, were determined by means of single-strand conformation polymorphism (SSCP) analysis of PCR products from the noncoding region of the viral genome. Representative SSCP patterns from HPV16 variants were further characterized by direct DNA sequencing of the PCR products. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox regression analysis. RESULTS: Prototype-like variants accounted for 79% of the HPV16 detected in university students and 86% of the virus detected in patients presenting to the sexually transmitted disease clinic. CIN 2-3 was confirmed by biopsy in nine of 57 HPV16-positive women attending the university and in 10 of 66 HPV16-positive women presenting to the sexually transmitted disease clinic. Among university students, those with HPV16 nonprototype-like variants were 6.5 (95% CI = 1.6-27.2) times more likely to develop CIN 2-3 than those with prototype-like variants. A similar association was observed among women presenting to the sexually transmitted disease clinic (RR = 4.5; 95% CI = 0.9-23.8). CONCLUSIONS: This study suggests that the risk of developing CIN 2-3 is not the same with all variants of HPV16 and that nonprototype-like variants confer a greater risk compared with prototype-like variants. The important genomic differences underlying this increased risk of CIN 2-3 remain to be determined.

Adolescent↗
PubMed2004

Long-term conservation of six duplicated structural genes in cephalopod mitochondrial genomes.

The complete nucleotide sequences of the mitochondrial (mt) genomes of three cephalopods, Octopus vulgaris (Octopodiformes, Octopoda, Incirrata), Todarodes pacificus (Decapodiformes, Oegopsida, Ommastrephidae), and Watasenia scintillans (Decapodiformes, Oegopsida, Enoploteuthidae), were determined. These three mt genomes encode the standard set of metazoan mt genes. However, W. scintillans and T. pacificus mt genomes share duplications of the longest noncoding region, three cytochrome oxidase subunit genes and two ATP synthase subunit genes, and the tRNA(Asp) gene. Southern hybridization analysis of the W. scintillans mt genome shows that this single genome carries both duplicated regions. The near-identical sequence of the duplicates suggests that there are certain concerted evolutionary mechanisms, at least in cephalopod mitochondria. Molecular phylogenetic analyses of mt protein genes are suggestive, although not statistically significantly so, of a monophyletic relationship between W. scintillans and T. pacificus.

Animals↗
PubMed1987

Continuing coevolution of virus and defective interfering particles and of viral genome sequences during undiluted passages: virus mutants exhibiting nearly complete resistance to formerly dominant defective interfering particles.

We quantitatively analyzed the interference interactions between defective interfering (DI) particles and mutants of cloned vesicular stomatitis virus passaged undiluted hundreds of times in BHK-21 cells. DI particles which predominated at different times in these serial passages always interfered most strongly (and very efficiently) with virus isolated a number of passages before the isolation of the DI particles. Virus isolated at the same passage level as the predominant DI particles usually exhibited severalfold resistance to these DI particles. Virus mutants (Sdi- mutants) isolated during subsequent passages always showed increasing resistance to these DI particles, followed by decreasing resistance as new DI particles arose to predominate and exert their own selective pressures on the virus mutant population. It appears that such coevolution of virus and DI particle populations proceeds indefinitely through multiple cycles of selection of virus mutants resistant to a certain DI particle (or DI particle class), followed by mutants resistant to a newly predominant DI particle, etc. At the peak of resistance, virus mutants were isolated which were essentially completely resistant to a particular DI particle; i.e., they were several hundred thousand-fold resistant, and they formed plaques of normal size and numbers in the presence of extremely high multiplicities of the DI particle. However, they were sensitive to interference by other DI particles. Recurring population interactions of this kind can promote rapid virus evolution. Complete sequencing of the N (nucleocapsid) and NS (polymerase associated) genes of numerous Sdi- mutants collected at passage intervals showed very few changes in the NS protein, but the N gene gradually accumulated a series of stable nucleotide and amino acid substitutions, some of which correlated with extensive changes in the Sdi- phenotype. Likewise, the 5' termini (and their complementary plus-strand 3' termini) continued to accumulate extensive base substitutions which were strikingly confined to the first 47 nucleotides. We also observed addition and deletion mutations in noncoding regions of the viral genome at a level suggesting that they probably occur at a high frequency throughout the genome, but usually with lethal or debilitating consequences when they occur in coding regions.

Amino Acid Sequence↗
PubMed1991

Why yeast?

Yeast is an apparently strange "model" for the human genome, but it works because of the high degree of conservation in evolution between the primitive eukaryote and mammals. Moreover, the genic concentration in yeast--with almost no noncoding introns--packs the entire yeast genome into 16 chromosomes with only 10% of the DNA of one human chromosome.

Genome, Human↗
PubMed1992

Characterization of the 5'-flanking region of the human brain-derived neurotrophic factor gene.

The 5'-flanking region of the human brain-derived neurotrophic factor (BDNF) gene was isolated from a human placental genomic library using the cDNA fragment for the 5'-noncoding region of human BDNF as a probe. A 3.2 Kbp genomic fragment containing the 5'-flanking region, the first exon and a portion of the first intron was isolated and sequenced. The transcriptional initiation site, identified by S1 nuclease mapping, was located 26 bp downstream from the TATA-like sequence. Several expression plasmids, in which the BDNF promoter regions were fused to the chloramphenicol acetyltransferase (CAT) gene, were constructed. Transient expression in human glioma Hs683 cells demonstrated that a fragment of about 0.5 Kbp from the transcriptional initiation site was sufficient for promoter activity.

Base Sequence↗
PubMed1992

A single base deletion in the 5' noncoding region of Theiler's virus attenuates neurovirulence.

Viral chimeras have been constructed through in vitro manipulations of the infectious cDNA clones of two prototypes of Theiler's murine encephalomyelitis virus: (i) the virulent GDVII strain and (ii) the less virulent BeAn and VL strains. Previous studies have suggested that the phenotypic differences in virulence between the BeAn and GDVII strains map to both the 5' noncoding and the coat protein regions of these viral genomes. It is shown here that attenuation mapped to the 5' noncoding region is due, at least in part, to an inadvertent deletion resulting from a cloning artifact of one C nucleotide out of four between positions 876 and 879 in the BeAn sequences. The in vitro growth characteristics in BHK-21 cells, however, do not reflect the large differences in neurovirulence between chimeras that are identical except for the deleted C. Another chimera with a mutation at position 877 and a deletion at 976 is also attenuated. The wild-type sequences from the less virulent strains BeAn and VL between nucleotides 1 and 933, in an otherwise GDVII chimera, do not attenuate virulence. Sequences of the 500 nucleotides of the 5' noncoding region proximal to the translation initiation codon were obtained for nine additional Theiler's virus strains. The attenuating deletions are discussed in the context of these sequences and the proposed secondary structures for the 5' noncoding region.

Animals↗
PubMed1991

The human Hb (mu) class glutathione S-transferases are encoded by a dispersed gene family.

The human glutathione S-transferases are products of a gene superfamily which consists of at least four gene families. The various glutathione S-transferase genes are located on different human chromosomes, and new gene(s) are still being added to the gene superfamily. We have characterized a cDNA in pGTH4 encoding human glutathione S-transferase subunit 4 (GST mu) and mapped its gene (or a homologous family member) on chromosome 1 at p31 by in situ hybridization. Genomic Southern analysis with the 3' noncoding region of the cDNA revealed at least four human DNA fragments with highly homologous sequences. Using a panel of DNAs from mouse-human somatic cell hybrids in genomic DNA hybridization we show that the Hb (or B) genes of human glutathione S-transferases are on three separate chromosomes: 1, 6, and 13. Therefore, the glutathione S-transferase B gene family, which encodes the Hb (mu) class subunits, is a dispersed gene family. The GST mu (psi) gene, whose expression is polymorphic in the human population, is probably located on chromosome 13. We propose that the GST mu (psi) gene was created by a transposition or recombination event during evolution. The null phenotype may have resulted from a lack of DNA transposition just as much as from the deletion of an inserted gene.

Animals↗
PubMed2000

Identification in the human candidate tumor suppressor gene HIC-1 of a new major alternative TATA-less promoter positively regulated by p53.

HIC-1 (hypermethylated in cancer 1), a BTB/POZ transcriptional repressor, was isolated as a candidate tumor suppressor gene located at 17p13.3, a region hypermethylated or subject to allelic loss in many human cancers and in the Miller-Dieker syndrome. The human HIC-1 gene is composed of two exons, a short 5'-untranslated exon and a large second coding exon. Recently, two murine HIC-1 isoforms generated by alternative splicing have been described. To determine whether such isoforms also exist in human, we have further analyzed the human HIC-1 locus. Here, we describe and extensively characterize a novel alternative noncoding upstream exon, exon 1b, associated with a major GC-rich promoter. We demonstrate using functional assays that the murine exon 1b previously described as coding from computer analyses of genomic sequences is in fact a noncoding exon highly homologous to its human counterpart. In addition, we report that the human untranslated exon is presumably a coding exon, renamed exon 1a, both in mice and humans. Both types of transcripts are detected in various normal human tissues with a predominance for exon 1b containing transcripts and are up-regulated by TP53, confirming that HIC-1 is a TP53 target gene. Thus, HIC-1 function in the cell is controlled by a complex interplay of transcriptional and translational regulation, which could be differently affected in many human cancers.

Alternative Splicing↗
PubMed1998

Large-scale analysis of hepatitis C virus serological typing assay: effectiveness and limits.

The HCV (hepatitis C virus) Serotyping 1-6 Assay (Murex Laboratories) was evaluated on 303 French HCV-infected patients. Serological typing results were compared to the genotypes obtained from sequence analyses of the 5' noncoding regions of the virus genome from 46 HCV-infected patients, and assay specificity was found to be high (97.6%). The serological typing assay, run in 257 consecutive HCV-infected patients, yielded an assay sensitivity lower (70.6%) than that previously reported. This finding was attributed mainly to nonreactive sera from human immunodeficiency virus (HIV)-positive patients (P < 0.001) and perhaps reflected cryoglobulin positivity in others. No anti-type 6 reactivity was detected, and the overall serological type distribution values for types 1 to 5 were 67.3, 7.9, 16.4, 6.6, and 0.9%, respectively. A higher prevalence of type 4 was noted among HIV-infected patients (P < 0.001). In addition, serotype 2 was significantly more frequent in cryoglobulinemia positive than in cryoglobulinemia-negative patients (P < 0.05). Although an initial high level (7%) of mixed serological typing reactivities was found, after predilution of serum only two mixed infections could be confirmed (0.9%). It is suggested, therefore, that mixed reactivities have to be interpreted carefully and retested with prediluted serum, particularly when the optical density of the reactivity is > 2.5 or remains > 0.4 after competition with all type-specific peptides. The high specificity and relatively good sensitivity even in immunocompromised patients obtained with this assay indicate that it can be used routinely. Because response to treatment is linked to HCV type, this assay could be used to identify HCV serotype to guide therapeutic decisions.

Case-Control Studies↗