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PubMed2006

Molecular epizootiology of avian infectious bronchitis in Russia.

Molecular characterization of infectious bronchitis viruses (IBVs) isolated between 1998 and 2002 from chickens in Russia was performed. More than 250 field samples were tested by reverse transcriptase-polymerase chain reaction using two sets of primers corresponding to the most conserved 3'-untranslated region and the most variable S1 gene region of the viral genome. Ninety-one IBV isolates were characterized by phylogenetic analysis of the S1 gene hypervariable region comprising 136 to 558 nucleotides. The major group of isolates (38 viruses) showed very close sequence relationship with strains of the Massachusetts genotype circulating in Russia since the early 1970s. The analysed region of the other 22 Russian IBVs was similar (from 89 to 98% identity) to that from the strains of European genotypes including D274 (nine isolates), 793/B (10 isolates), and B1648, 624/I and Italy-02 (one isolate in each group). Two isolates from very distant geographic locations in Russia (Far East and the European part) clustered together with Chinese strains of QXIBV genotype. None of the remaining 27 Russian isolates showed a close sequence relationship with known IBV strains available in sequence databases. The majority of these variant viruses clustered into the six novel Russian genotypes, often correlating with their geographic location. The remaining five of them were placed outside these unique groups, also representing new genotypes. These data for the first time demonstrated the high genetic diversity of IBV isolates circulating in Russia.

Animals↗
PubMed1988

Point mutations cause the somatic diversification of IgM and IgG2a antiphosphorylcholine antibodies.

The genetic mechanism responsible for the somatic diversification of two mAbs was determined. The two PC-binding hybridomas were representative of events early and late in the immune response. The P28 cell line that produces an IgM antibody and thus represents events early in the immune response, was found to have 3 bp changes in its heavy chain variable (VH) region, with some changes in antibody affinity or specificity. The RP93 cell line that produces an IgG2a antibody and thus represents later events in the immune response, was found to have 9 bp changes in its VH region resulting in decreased affinity for PC and altered specificity. Oligonucleotides specific for linked base changes in the second hypervariable regions of both of these antibodies were used to look for previously undescribed V regions or other donor sequences that could have been responsible for these base changes. Since no donor sequences were found, we have concluded that somatic point mutation rather than gene conversion, V region replacement or the expression of an unidentified germline VH region gene is truly responsible for at least some of the somatic diversification of these antibodies.

Amino Acid Sequence↗
PubMed1993

Conserved motifs in rheumatoid arthritis synovial tissue T-cell receptor beta chains.

Rheumatoid arthritis is genetically linked to major histocompatibility complex (MHC) molecules (HLA-DR4 and related molecules) and characterized pathologically by high levels of HLA-DR expression and infiltration of proliferative of synovial tissue with CD4+ T lymphocytes. T-lymphocyte activation is driven by specific signaling through polymorphic alpha/beta T-cell receptors (TCRs) that are reactive with antigen-MHC complexes present at the sites of inflammation. We are interested in characterizing rheumatoid TCRs molecularly to ascertain potential binding surfaces for antigen+MHC in synovial tissue. Accordingly, we have recently investigated the TCR alpha and beta chain heterogeneity in a series of 10 rheumatoid synovia obtained at the time of joint surgery. The most frequently detected V beta families were V beta 12, 14, and 17, each of which was found in 80% of specimens. We report here the molecular cloning and sequence analysis of 20 cloned V beta segments amplified with a V beta 14 family-specific TCR primer, and six cloned V beta segments amplified with a V beta 17 family-specific TCR primer from four rheumatoid synovia. Comparison with the data base revealed that these sequences belonged to the closely related V beta 3, V beta 14, and V beta 17 families. Dominant clones were apparent in two of the individuals by the presence of identical V-D-J regions, suggesting an antigen-driven process. Amino acid sequence analysis revealed a conserved motif in the putative fourth hypervariable region or CDR4. Molecular modeling of this epitope suggests that charged side chains are available for binding to ligand structures (e.g., antigen, MHC, or superantigen). We suggest this epitope may play a role in the molecular pathogenesis of rheumatoid arthritis.

Amino Acid Sequence↗
PubMed2004

The S haplotype-specific F-box protein gene, SFB, is defective in self-compatible haplotypes of Prunus avium and P. mume.

Many Prunus species, including sweet cherry and Japanese apricot, of the Rosaceae, display an S-RNase-based gametophytic self-incompatibility (GSI). The specificity of this outcrossing mechanism is determined by a minimum of two genes that are located in a multigene complex, termed the S locus, which controls the pistil and pollen specificities. SFB, a gene located in the S locus region, encodes an F-box protein that has appropriate S haplotype-specific variation to be the pollen determinant in the self-incompatibility reaction. This study characterizes SFBs of two self-compatible (SC) haplotypes, S(4') and S(f), of Prunus. S(4') of sweet cherry is a pollen-part mutant (PPM) that was produced by X-ray irradiation, while S(f) of Japanese apricot is a naturally occurring SC haplotype that is considered to be a PPM. DNA sequence analysis revealed defects in both SFB(4') and SFB(f). A 4 bp deletion upstream from the HVa coding region of SFB(4') causes a frame-shift that produces transcripts of a defective SFB lacking the two hypervariable regions, HVa and HVb. Similarly, the presence of a 6.8 kbp insertion in the middle of the SFB(f) coding region leads to transcripts for a defective SFB lacking the C-terminal half that contains HVa and HVb. As all reported SFBs of functional S haplotypes encode intact SFB, the fact that the partial loss-of-function mutations in SFB are present in SC mutant haplotypes of Prunus provides additional evidence that SFB is the pollen S gene in GSI in Prunus.

Amino Acid Sequence↗
PubMed1998

Quasispecies nature of hepatitis C virus (HCV) in patients with chronic hepatitis C with mixed HCV subtypes.

The quasispecies nature of hepatitis C virus (HCV) in patients with mixed HCV subtype infection was compared with that in patients with single HCV subtype infection. The number of HCV quasispecies was compared between 35 patients with mixed HCV subtype infection and 83 patients with single subtype infection. Subtype was determined by primers deduced from the core region and by line probe assay respectively. The number of quasispecies was evaluated by polymerase chain reaction amplification of hypervariable region 1 and by fluorescence single-strand conformation polymorphism analysis. There was no difference in clinical background between patients with mixed subtype infection and patients with single subtype infection. The number of quasispecies in patients with multiple subtype HCV infection was larger than in patients with single subtype HCV infection. The immunologic environments which allow the coexistence of more HCV quasispecies in patients with multiple HCV subtype infection differs from that in patients with single HCV subtype infection.

Adult↗
PubMed2005

Mitochondrial sequence variation in the Guahibo Amerindian population from Venezuela.

New data were obtained on mitochondrial DNA (mtDNA) from Guahibo from Venezuela, a group so far not studied using molecular data. A population sample (n = 59) was analyzed for mtDNA variation in two control-region hypervariable segments (HV1 and HV2) by sequencing. The presence or absence of a 9-bp polymorphism in the COII/tRNA(Lys) region was studied by direct amplification and electrophoretic identification. Thirty-eight variable sites were detected in regions HV1 and HV2, defining 26 mtDNA lineages; 23.7% of these were present in a single individual. The 9-bp deletion was found in 3.39% of individuals. Nucleotide and haplotype diversities were relatively high compared with other New World populations. The identified sequence haplotypes were classified into four major haplogroups (A-D) according to previous studies, with high frequencies for A (47.46%) and C (49.15%), low frequency for B (3.39%), and an absence of D.

Base Sequence↗
PubMed1997

Hormone-sensitive lipase (Lipe): sequence analysis of the 129Sv mouse Lipe gene.

Hormone-sensitive lipase (Lipe) catalyzes both the release lease of fatty acids from storage triglycerides in adipocytes and the liberation of cholesterol from cholesterol esters in steroidogenic tissues. Lipe activity is regulated in a tissue-, development- and hormone-specific fashion, the latter in large part by serine phosphorylation. We cloned and sequenced the Lipe gene from the 129Sv strain mouse, including 2.7 kb of the 5' nontranslated region. The primary transcript of the 129Sv Lipe locus spans 9.6 kb and contains 9 exons. We studied the curious hypervariable region immediately 5' to the regulatory serine residues by aligning the peptide and nucleic acid sequences of mouse, human, and rat Lipe. We propose that much of the variability is attributable to differences in the copy number of a 12-nucleotide repeat that shifts the intron 7 acceptor splice site. Introns 1 and 7 contain B1 elements, which in intron 7 are immediately adjacent to a tetranucleotide repeat. The mouse Lipe promoter region contains numerous potential binding motifs for factors implicated in adipose tissue expression and hormone responsiveness including adipocyte determination- and differentiation-dependent factor 1 (ADD1/SREBP1).

Amino Acid Sequence↗
PubMed1987

Minisatellite mapping in manic depression.

Hypervariable regions of DNA exist at many discrete loci in the human genome. Variations in the length of specific classes of hypervariable DNA termed "minisatellite" sequences may be detected by hybridisation of radioactive probes composed of a common 10-15 base pair repeat or "core" sequence which is shared by each of the minisatellite loci. Such a procedure was used to perform linkage analysis on a kindred in which a disease allele causing manic depression appeared to be segregating as an autosomal dominant. Results indicate no apparent linkage between a manic depression allele and at least 20 hypervariable genetic loci which acted as markers. However, because of the hypervariability of the minisatellite loci these results do not preclude similar analyses of other manic depressive pedigrees being productive because each such family will have distinct observable minisatellite alleles at loci specific to that family. The method could be usefully applied to the genetic analysis of other psychiatric disorders where heterogeneity is suspected and where a single autosomal major gene locus appears to be responsible for causing multiple cases within a single kindred.

Base Sequence↗
PubMed1988

Envelope sequences of two new United States HIV-1 isolates.

One of the striking molecular aspects of the human T-cell lymphotropic virus type III (HTLV-III) (now called HIV-1) is an unusually large variability in the env genes of different isolates. These differences are clustered primarily within the coding sequences for the large envelope protein and are interspersed among regions within the env gene of relative constancy. Differences among the envelopes of isolates from Africa are so far greater than those among U.S. isolates, but few U.S. isolates have been characterized to date. We report the sequence of the env gene of two U.S. isolates [HTLV-III(MN) and (SC)] and compare them with previously characterized isolates. These two isolates differ substantially from all previously described isolates, especially in the region coding for the large envelope proteins. The env genes of the two new HIV-1 isolates contain conserved and hypervariable regions similar to what has been reported for other isolates, helping to further define those regions. A comparison of the envelope sequences of all the U.S. isolates shows that the similarity between any two ranges from 81 to 85% [except for LAV(BRU) and HTLV-III(BH10) which are 97% similar]. Similar analyses of the African (Zairean) isolates give significantly lower values [71 to 78%, except for 88% between LAV(ELI) and Z6]. This suggests that the African isolates diverged earlier than the U.S. isolates or that transmission of the virus has been more rapid in Africa. Two previous presumptive Haitian isolates are similar to each other and to the U.S. isolates to the same degree as are other U.S. isolates, but differ more markedly from the African isolates suggesting a common lineage of Haitian and U.S. HIV-1 isolates.

Amino Acid Sequence↗
PubMed2004

The two subfamilies of rice glutelin differ in both primary and higher-order structures.

Rice glutelin, which accounts for 70-80% of the total proteins of the seeds, consists of two nutritionally different subfamilies (A and B types). Although the similarity in primary sequences between the two subfamilies is as high as 60%, we established conditions to discriminate the two subfamilies when low amounts of antigen are analyzed by immunoblot methods. The glutelin alpha polypeptides can be resolved into six bands labeled alpha1 to alpha6 by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Gel filtration analysis showed that glutelin exists as a polymerized and a smaller molecular weight form. Immunoblot analysis of SDS-PAGE resolved polypeptides showed that alpha2, alpha3, and alpha4 are an A type and that these A types as well as alpha1, a B type, are polymerized. The polymerization tendency clearly differed between the two subfamilies except for alpha1, which may be derived from GluB-4 as suggested by analysis using Escherichia coli expression systems of glutelin cDNA regions corresponding to alpha polypeptides. GluB-4 and all the A type subunits have an extra Cys residue in the hypervariable regions, corresponding to the C-terminal region of alpha polypeptide. Accordingly, the extra Cys residue is hypothesized to be responsible for the polymerization of glutelin.

Amino Acid Sequence↗
PubMed2002

Sequencing strategy of mitochondrial HV1 and HV2 DNA with length heteroplasmy.

We describe a method to obtain reliable mitochondrial DNA (mtDNA) sequences downstream of the homopolymeric stretches with length heteroplasmy in the sequencing direction. The method is based on the use of junction primers that bind to a part of the homopolymeric stretch and the first 2-4 bases downstream of the homopolymeric region. This junction primer method gave clear and unambiguous results using samples from 21 individuals with length heteroplasmy in the hypervariable regions HV1, HV2 or both. The method is of special value for forensic casework, because sequencing of both strands of an mtDNA region is preferable in order to reduce ambiguities in sequence determination.

DNA, Mitochondrial↗
PubMed1992

Polyreactive IgM antibodies generated from autoimmune mice and selected for histone-binding activity.

A panel of histone-reactive IgM mAbs was obtained from mice belonging to various spontaneously autoimmune strains. Most of these antibodies were polyreactive, i.e. they showed binding to other cationic antigens (poly-L-lysine, lysozyme, cytochrome c) or to cytoskeletal proteins (actin, myosin, vimentin). The variable regions of these antibodies were encoded by V genes and gene segments belonging to various families. Their H chain third hypervariable regions were unusual in that the D segments were read in all three possible reading frames in contrast to most conventional antibodies and other polyreactive antibodies obtained from normal mice.

Amino Acid Sequence↗
PubMedDate not supplied

[Structural and functional organization of hepatitis C virus genome].

The review gives recent data on the structure of hepatitis C virus genome. Linear RNA comprises one translated and two nontranslated regions: 5'UTR and 3'UTR. Translation of viral RNA gives rise to a single polyprotein precursor that contains structural and nonstructural regions. The structural region comprises one nucleocapsid core-protein and two envelope proteins known as E1 and E2. E2 protein includes two hypervariable regions: HVR1 and HVR2. The nonstructural region consists of 7 proteins: p7 (NS1), NS (metalloproteinase), NS (serine protease/ helicase), NS4A (co-factor protease, co-factor RNA-dependent RNA polymerase), and NS4B, NS5A, NS5B (RNA-dependent RNA polymerase). NS5A includes ISDR (interferon-sensitivity-determining region).

Carrier Proteins↗
PubMed1998

Rapid mitochondrial DNA typing using restriction enzyme digestion of polymerase chain reaction amplicons followed by capillary electrophoresis separation with laser-induced fluorescence detection.

The polymorphic control region of mitochondrial DNA (mtDNA) is becoming more commonly used in forensic applications to differentiate among individuals in a population. Two hypervariable regions (HV1 and HV2) are often sequenced following amplification of the mtDNA via the polymerase chain reaction (PCR). More rapid screening assays would reduce both the effort and the expense of comparing two samples. A methodology has been developed that first uses restriction endonuclease digestion of the PCR-amplified mtDNA using RsaI and MnlI and then capillary electrophoresis (CE) to separate and size the PCR-RFLP fragments. This rapid procedure offers an alternative method for screening of polymorphisms in amplified mtDNA samples. In addition, the presence of a T-->C transition at position 16189, which gives rise to the so-called "C-stretch" in HV1, may be predicted from the presence of nonspecific PCR products in the CE results.

Computer Simulation↗
PubMed1989

Sequential anti-idiotypes define reciprocal idiotopes on the same anti-DNA antibody.

Sequential anti-idiotypes have defined a pair of idiotypes with an idiotype-anti-idiotype relationship to each other in the variable region of the monoclonal anti-DNA antibody 16/6. A rabbit immunized with 16/6 made an antibody-1 (anti-Id-16/6R) and an antibody-2 (anti-anti-Id-16/6 or anti-anti-Id 16/6M). The latter bound to M-2, a monoclonal mouse anti-Id-16/6. M-2 was used to immunize a second mouse, which produced M-16. The variable region of M-16 mimics an antigenic surface on Id-16/6 and binds to a peptide contained within the first hypervariable region of the light chain of 16/6. The complementary idiotypes of 16/6 represent a reciprotope, an idiotype/anti-idiotype pair within the variable region of the same immunoglobulin molecule which may have functional importance.

Animals↗
PubMed1988

A single amino acid substitution in the human histocompatibility leukocyte antigen DR3 beta chain selectively alters antigen presentation.

Activation of T lymphocytes by immunogenic peptides bound to HLA molecules is a central event in the generation of an immune response. To determine the sites on HLA molecules involved in this process, we isolated mutant EBV-transformed B cell clones that express altered HLA-DR3 molecules. One mutant has lost the ability to stimulate a T cell clone specific for a mycobacterial protein, but retains the ability to stimulate other antigen-specific T cells. The DNA sequence of the complete DR alpha and beta coding regions revealed a single nucleotide change resulting in a glutamic acid to lysine substitution at amino acid 9 in the first hypervariable region of the DR beta chain. These results are discussed in relation to a recently proposed model of class II molecule structure.

Amino Acid Sequence↗
PubMed2002

[Genetic variation characteristics of the envelope region of hepatitis C virus in the patients with chronic hepatitis].

OBJECTIVE: To study the association of the envelope region variation of hepatitis C virus (HCV) with the chronicity of HCV infection. METHODS: Acute phase plasma samples from three injection drug users who acquired HCV infection during six month follow-up and three patients with chronic hepatitis C were obtained. A 573 bp fragment containing the 5' half of E1 and 3' half of E2 were amplified by nested reverse transcription polymerase chain reaction (RT-PCR). For each cloned cDNAs were examined by a method that combined heteroduplex (HD) analysis and a single-stranded conformational polymorphism (SSCP) assay to assess quasispecies complexity and optimize selection of clones with unique gel shift patterns for sequencing. The ratio of nonsynonymous to synonymous substitution (dN/dS) within each sample was evaluated as an indicator of relative selective pressure. Amino acid sequences were analyzed for signature patterns and glycosylation signals. RESULTS: Quasispecies complexity and E2 dN/dS ratio were higher in those with chronic hepatitis, in whom a trend toward more numbers of nonsynonymous mutations was detected at the E2. 1.02% (1.33/130) and 8.46% (11/130) amino acids within the E2 region mutated in chronic hepatitis and acute hepatitis, whereas within the E1 region 2.74% and 1.09% amino acids replaced among chronic and acute hepatitis respectively. Some consistent amino acids were detected, although the hypervariable region 1 (HVR1) had a higher variability in subjects with chronic infection. CONCLUSIONS: HCV persistence is associated with a complex quasispecies and host immune selection to HVR1.

Genetic Variation↗
PubMed1997

The nucleoside-specific Tsx channel from the outer membrane of Salmonella typhimurium, Klebsiella pneumoniae and Enterobacter aerogenes: functional characterization and DNA sequence analysis of the tsx genes.

The Escherichia coli tsx gene encodes an integral outer-membrane protein (Tsx) that functions as a substrate-specific channel for deoxynucleosides and the antibiotic albicidin, and also serves as a receptor for bacteriophages and colicins. We cloned the structural genes of the Tsx proteins from Salmonella typhimurium, Klebsiella pneumoniae and Enterobacter aerogenes and expressed them in an E.coli tsx mutant. The heterologous Tsx proteins fully substituted the E.coli Tsx protein with respect to its function in deoxynucleoside and albicidin uptake, and as receptor for colicin K. The Tsx proteins from K. pneumoniae and Ent. aerogenes were also proficient as receptors for several Tsx-specific bacteriophages, whereas the corresponding protein from S. typhimurium did not confer sensitivity against these phages. The nucleotide sequence of the tsx genes from S. typhimurium, K. pneumoniae and Ent. aerogenes was established. Each of the Tsx proteins is initially synthesized with typical bacterial signal sequence peptides and the predicted mature forms of the Tsx proteins have a calculated M(r) of 30,567 (265 residues), 31,412 (272 residues) and 31,477 (272 residues), respectively. Multiple sequence alignments between the Tsx proteins showed a high degree of sequence identity and revealed the presence of four hypervariable regions, which are thought to constitute segments of the polypeptide chain exposed at the cell surface. Most notable was a deletion of 8 amino acids in one of these hypervariable domains in the S. typhimurium Tsx protein. When this deletion was introduced by site-directed mutagenesis into the corresponding region of the E.coli tsx gene, the mutant Tsx-515 protein lost its phage receptor function but still served as a colicin K receptor and as a substrate-specific channel, indicating that the region between residues 198 and 207 might be part of the bacteriophage receptor area. Multiple sequence alignments, structural predictions and the properties of previously characterized Tsx missense mutants were taken into account to develop a two-dimensional model for the topological organization of the Tsx protein within the outer membrane.

Amino Acid Sequence↗