Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “hypervariable regions”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources
PubMed2002

Phylogenetic analysis of Brassiceae based on the nucleotide sequences of the S-locus related gene, SLR1.

Nucleotide sequences of orthologs of the S-locus related gene, SLR1, in 20 species of Brassicaceae were determined and compared with the previously reported SLR1 sequences of six species. Identities of deduced amino-acid sequences with Brassica oleracea SLR1 ranged from 66.0% to 97.6%, and those with B. oleracea SRK and SLR2 were less than 62% and 55%, respectively. In multiple alignment of deduced amino-acid sequences, the 180-190th amino-acid residues from the initial methionine were highly variable, this variable region corresponding to hypervariable region I of SLG and SRK. A phylogenetic tree based on the deduced amino-acid sequences showed a close relationship of SLR1 orthologs of species in the Brassicinae and Raphaninae. Brassica nigra SLR1 was found to belong to the same clade as Sinapis arvensis and Diplotaxis siifolia, while the sequences of the other Brassica species belonged to another clade together with B. oleracea and Brassica rapa. The phylogenetic tree was similar to previously reported trees constructed using the data of electrophoretic band patterns of chloroplast DNA, though minor differences were found. Based on synonymous substitution rates in SLR1, the diversification time of SLR1 orthologs between species in the Brassicinae was estimated. The evolution and function of SLR1 and the phylogenetic relationship of Brassiceae plants are discussed.

Journal Article↗
PubMed1997

Hydropathic characteristics of adenovirus hexons.

The complete nucleotide sequence and the predicted amino acid sequence of the adenovirus type 7 hexon gene were determined. The hydropathy of the hexon proteins from human adenovirus types 2, 3, 4, 5, 7, 12, 16, 40, 41, and 48, bovine adenovirus type 3, murine adenovirus type 1, and avian adenovirus types 1 and 10 was analysed. The presence of purines and pyrimidines in the second position of the codons was correlated to hydrophilicity and hydrophobicity, respectively. Comparison of the hydrophilicity plots of eight hexons showed seven hypervariable regions to be distributed on the surface. A large portion of the hypervariable regions manifests hydrophilicity. The strength of the surface charge accumulated on the hydrophilic and hydrophobic regions correlated to the tissue tropism of the different adenovirus types. Analysis of codon usage for adenovirus hexons showed that among synonymous codons those with cytidine in the third position were preferably used to a great extent. Analysis of the nucleotide and amino acid sequence pair distances and the phylogenetic tree of 14 hexon proteins showed members of subgenera B, D and E to be closely related, especially Ad4 and Ad16, and subgenus A to be closely related to subgenus F.

Adenoviruses, Human↗
PubMed1986

Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS.

To determine the extent and nature of genetic variation present in independent isolates of HTLV-III/LAV, the nucleotide sequences of the entire envelope gene and parts of gag and pol were determined for two AIDS viruses. The results indicated that variation throughout the viral genome is extensive and that the envelope gene in particular is most highly variable. Within the envelope, changes were most prevalent within the extracellular region where clustered nucleotide substitutions and deletions/insertions were evident. Based on predicted secondary protein structure and hydrophilicity, these hypervariable regions represent potential antigenic sites. In contrast to the hypervariable regions, other sequences in the extracellular envelope and the overall envelope structure (including 18 of 18 cysteine residues), as well as most of the transmembrane region, were highly conserved.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Intraspecific nucleotide sequence variability surrounding the origin of replication in human mitochondrial DNA.

We have cloned the major noncoding region of human mitochondrial DNA (mtDNA) from 11 human placentas. Partial nucleotide sequences of five of these clones have been determined and they share a maximum of 900 bp around the origin of H-strand replication. Alignment of these sequences with others previously determined has revealed a striking pattern of nucleotide substitutions and insertion/deletion events. The level of sequence divergence significantly exceeds the reported estimates of divergence in coding regions. Two particularly hypervariable regions have also been defined. More than 96% of the base changes are transitions, and length alterations have occurred exclusively by addition or deletion of mono-or dinucleotide segments within serially repeating stretches. This region of the mitochondrial genome, which contains the initiation sites for replication and transcription, is the least conserved among species with respect to both sequence and length (Anderson et al., 1981; Walberg and Clayton, 1981). Despite this overall lack of primary sequence conservation, several consistencies appear among the available mammalian mtDNA sequences within this region. Between species, a conserved linear array of characteristic stretches exists which nonetheless differ in primary sequence. Among humans, several conserved blocks of nucleotides appear within domains deleted from the mtDNA of other species. These observations are consistent with both a species-specificity of nucleotide sequence, and a preservation of the necessary genetic functions among species. This provides a model for the evolution of protein-nucleic acid interactions in mammalian mitochondria.

Amino Acid Sequence↗
PubMed1999

Mother-to-infant transmission of hepatitis C virus: molecular evidence of superinfection by homologous virus in children.

BACKGROUND/AIM: Vertical transmission of hepatitis C virus (HCV) is well established but its incidence is low. To assess the molecular evidence of mother-to-infant transmission or intrafamilial transmission of HCV, the NS5 B region and the hypervariable region 1 (HVR1) of the E2/NS1 region of the HCV genome from each member of a family were investigated. METHODS: A 35-year-old mother with chronic hepatitis C virus infection and her four infected boys were studied. The same HCV 1a genotype was found in all five. Phylogenetic analysis was done by the neighbor-joining, the maximum likelihood, and the maximum parsimony methods. RESULTS: Comparison of the phylogenetic trees in the NS5B and HVR1 regions showed that the sequences in the children were more closely related to the population of variants of their own mother than to any genotype la sequence available in the databases. However, four HVR1 clones from two brothers (E2 and E3) had a strong homology, but were significantly divergent from the variants of the mother. CONCLUSIONS: These results suggest that a cluster of HCV strains exists in the family and that E3 could have been superinfected by E2 HCV strains and reciprocally. In conclusion, phylogenetic analysis through variable regions of the genome suggests that at least two modes of transmission are involved in this family: perinatal and horizontal.

Adult↗
PubMed1993

Interactions of three domains distinguishing the Ras-related GTP-binding proteins Ypt1 and Sec4.

The genes SEC4 and YPT1 encode Ras-related GTP-binding proteins in the yeast Saccharomyces cerevisiae. Ypt1 is necessary for vesicular transport from the endoplasmic reticulum to the Golgi, whereas Sec4 is required for fusion of post-Golgi secretory vesicles to the plasma membrane. Recently, three structural domains have been proposed to specify the stage in cellular transport at which members of the Sec4/Ypt1/Rab family act: the effector domain, the C-terminal hypervariable region, and a region corresponding to loop 7 in the structure of p21ras (ref. 8). Here we use Sec4/Ypt1 chimaeras to show that these three regions cooperate to specify Ypt1 function and that the C-terminal hypervariable region is needed for Ypt1 localization to the Golgi. Unexpectedly, we found that a single chimaera can function as either Ypt1 or Sec4 without missorting carboxypeptidase Y or invertase.

Amino Acid Sequence↗
PubMed2001

Identifying allogeneic platelets by resolution of point mutations in mitochondrial DNA using single-stranded conformational polymorphism PCR.

BACKGROUND: The purpose of this study was to evaluate single-stranded conformational polymorphism (SSCP)-PCR utilizing two different regions of mitochondrial DNA (mtDNA) as a method to discriminate between donor platelets and recipient cells. STUDY DESIGN AND METHODS: Twenty-eight mixtures of platelets (1:1 ratio) were prepared from eight randomly selected persons to simulate donor-recipient combinations after allogeneic platelet transfusion. The mtDNA was extracted from each donor and each prepared mixture. Four primer pairs were designed to amplify two regions of mtDNA, hypervariable region (HVR) 1 and 2. An SSCP-PCR method was developed to analyze the four different amplicons. In addition, the amplified DNA samples containing HVR1 and HVR2 mtDNA of the eight persons were sequenced by using dye-terminator cycle sequencing to determine mtDNA polymorphisms. RESULTS: With four different primer pairs and SSCP-PCR, it was possible to discriminate between donor and recipient DNA in all 28 combinations. DNA sequencing confirmed that the suspected differences were localized within the amplicons examined by SSCP-PCR. CONCLUSION: SSCP-PCR analysis targeting the HVR1 and HVR2 mtDNA is a promising new method to potentially identify donor cells on the basis of mtDNA polymorphisms. The method does not require prior knowledge of sequence differences between donor and recipient and can be optimized to quantify the amount of residual transfused allogeneic platelets.

Blood Donors↗
PubMed1987

Diversity and structure of human T-cell receptor alpha-chain variable region genes.

The nucleotide sequences of 27 T-cell receptor alpha-chain variable region (V alpha)-containing cDNA clones isolated from a cDNA library derived from human peripheral blood lymphocytes were determined. Eighteen different V alpha and 26 different joining (J alpha) gene segments are utilized in these clones. The V alpha gene segments belong to 12 different subfamilies, each containing from one to seven members. Comparisons with the 16 different V alpha and 21 different J alpha sequences previously reported suggest that the germ-line repertoires for these gene segments are greater than previously estimated. Flexibility in the sites of gene segment joining and possibly N-region diversification also contribute to human alpha-chain diversity. Comparisons of human V alpha regions indicate a high degree of variability spread uniformly across the entire V alpha region without obvious hypervariable regions. However, amino acids important for the maintenance of V gene structure are conserved.

Amino Acid Sequence↗
PubMed1999

A complex ligase ribozyme evolved in vitro from a group I ribozyme domain.

Like most proteins, complex RNA molecules often are modular objects made up of distinct structural and functional domains. The component domains of a protein can associate in alternative combinations to form molecules with different functions. These observations raise the possibility that complex RNAs also can be assembled from preexisting structural and functional domains. To test this hypothesis, an in vitro evolution procedure was used to isolate a previously undescribed class of complex ligase ribozymes, starting from a pool of 10(16) different RNA molecules that contained a constant region derived from a large structural domain that occurs within self-splicing group I ribozymes. Attached to this constant region were three hypervariable regions, totaling 85 nucleotides, that gave rise to the catalytic motif within the evolved catalysts. The ligase ribozymes catalyze formation of a 3',5'-phosphodiester linkage between adjacent template-bound oligonucleotides, one bearing a 3' hydroxyl and the other a 5' triphosphate. Ligation occurs in the context of a Watson-Crick duplex, with a catalytic rate of 0.26 min(-1) under optimal conditions. The constant region is essential for catalytic activity and appears to retain the tertiary structure of the group I ribozyme. This work demonstrates that complex RNA molecules, like their protein counterparts, can share common structural domains while exhibiting distinct catalytic functions.

Animals↗
PubMed2002

Extensive linkage disequilibrium in small human populations in Eurasia.

The extent of linkage disequilibrium (LD) was studied in two small food-gathering populations-Evenki and Saami-and two larger food-producing populations-Finns and Swedes-in northern Eurasia. In total, 50 single-nucleotide polymorphisms (SNPs) from five genes were genotyped using real-time pyrophosphate DNA sequencing, whereas 14 microsatellites were genotyped in two X-chromosomal regions. In addition, hypervariable region I of the mtDNA was sequenced to shed light on the demographic history of the populations. The SNP data, as well as the microsatellite data, reveal extensive levels of LD in Evenki and Saami when compared to Finns and Swedes. mtDNA-sequence variation is compatible with constant population size over time in Evenki and Saami but indicates population expansion in Finns and Swedes. Furthermore, the similarity between Finns and Swedes in SNP allele- and haplotype-frequency distributions indicate that these two populations may share a recent common origin. These findings suggest that populations such as the Evenki and the Saami, rather than the Finns, may be particularly suited for the initial coarse mapping of common complex diseases.

Chromosome Mapping↗
PubMed2003

Molecular epidemiology and forensic genetics: application to a hepatitis C virus transmission event at a hemodialysis unit.

Molecular phylogenetic analyses are frequently used in epidemiologic testing, although only occasionally in forensics. Their acceptability is hampered by a lack of statistical confidence in the conclusions. However, maximum likelihood testing provides a sound statistical framework for the testing of phylogenetic hypotheses relevant for forensic analysis. We present the results of applying this method to a small hepatitis C outbreak produced in a hospital hemodialysis unit that involved 6 patients. Polymerase chain reaction products from a 472-nt fragment of the E1-E2 region, including the hypervariable region, HVR-1, of the hepatitis C virus genome were cloned, and an average of 10 clones/patient and from 11 additional control patients were sequenced. The method allows a statistical evaluation that the likelihood of each sample belonging or not to a given group, a question of relevance in many forensic and epidemiological analyses of molecular sequences.

Cross Infection↗
PubMed2004

Characteristics of a human monoclonal autoantibody to the thyrotropin receptor: sequence structure and function.

The properties of a human monoclonal antibody to the thyrotropin receptor (TSHR) (M22) with the characteristics of patient sera thyroid stimulating autoantibodies is described. Similar concentrations (pmol/L) of M22 Fab and porcine TSH had similar stimulating effects on cyclic adenosine monophosphate (cAMP) production in TSHR-transfected Chinese hamster ovary cells whereas higher doses of intact M22 immunoglobulin G (IgG) were required to cause the same level of stimulation. Patient sera containing TSHR autoantibodies with TSH antagonist (blocking) activity inhibited M22 Fab and IgG stimulation in a similar way to their ability to block TSH stimulation. Thyroid-stimulating monoclonal antibodies (TSmAbs) produced in mice inhibited 125I-TSH binding and 125I-M22 Fab binding to the TSHR but the mouse TSmAbs were less effective inhibitors than M22. These competition studies emphasized the close relationship between the binding sites on the TSHR for TSH, TSHR autoantibodies with TSH agonist activity, and TSHR autoantibodies with TSH antagonist activity. Recombinant M22 Fab could be produced in Escherichia coli and the recombinant and hybridoma produced Fabs were similarly active in terms of inhibition of TSH binding and cAMP stimulation. The crystal structure of M22 Fab was determined to 1.65 A resolution and is that of a standard Fab although the hypervariable region of the heavy chain protrudes further from the framework than the hypervariable region of the light chain. The M22 antigen binding site is rich in aromatic residues and its surface is dominated by acidic patches on one side and basic patches on the other in agreement with an important role for charge-charge interactions in the TSHR-autoantibody interaction.

Animals↗
PubMed1975

Structure and specificity of antibody molecules.

The structure of the Fab' fragment of a human myeloma protein (IgG1 (lambda) New) has been determined by X-ray crystallographic analysis to a nominal resolution of 0.2 nm. Each of the structure subunits corresponding to the variable and to the constant homology regions of the light and heavy polypeptide chains contains two irregular beta-sheets which are roughly parallel to each other and surround a tighly packed interior of hydrophobic side chains. The regions of the hypervariable sequences in the light and heavy chains occur in close spatial proximity at one end of the molecule, defining the active site of IgG New. The role of these hypervariable regions in defining the size and shape of the active site of different immunoglobulins is discussed on the basis of the three-dimensional model of Fab' New. Several ligands that bind to the active centre of IgG New have been used to obtain crystalline ligand-Fab' New complexes which were investigated by difference Fourier maps. These studies are analysed in terms of the biological function and specificity of antibodies.

Amino Acid Sequence↗
PubMed1994

Nucleotide sequence of hepatitis C virus (type 3b) isolated from a Japanese patient with chronic hepatitis C.

The genomic sequences of many hepatitis C virus (HCV) isolates have been reported and a variety of virus genotypes have been classified based on homology in the conserved regions. We have previously identified five distinct genotypes (1a, 1b, 2a, 2b and 3b) in Japanese patients with chronic HCV infection by comparing the sequences of the NS5 region. The complete nucleotide sequence for five genotypes (1a, 1b, 1c, 2a and 2b) have already been reported and we report here the complete nucleotide sequence of genotype 3b. The isolate (HCV Tr) was 9439 nucleotides long, excluding the poly(U) tract at its 3' end, and encodes a single long open reading frame of 3023 amino acids. Total nucleotide sequence homologies were 68.4 to 68.7%, 68.3 to 69.0%, 67.2%, 65.8% and 65.6% compared with type 1a, 1b, 1c, 2a and 2b genomes, respectively. The amino acid sequences of these five genotypes were highly homologous in the core, NS3 and NS5B regions, but the E2/NS1 region, which contains hypervariable regions 1 and 2, and the NS5A region were poorly conserved. Although it was possible to detect antibody against the relatively homologous core and NS3 regions by ELISA, the presence of divergent protein structures must be taken into account in the development of a vaccine.

Amino Acid Sequence↗
PubMed1995

Early-onset pauciarticular juvenile chronic arthritis is associated with a mutation in the Y-box of the HLA-DQA1 promoter.

Early-onset pauciarticular juvenile chronic arthritis (EOPA-JCA) has associations with different alleles of the MHC region (HLA-A2, DR5, 6, 8, DQA1*0401, *0501, *0601 and DPB1*0201). All susceptible DQA1 alleles carry an exclusive sequence motif. MHC-class II gene expression is controlled by 5' flanking upstream regulatory regions (URR). A hypervariable region in the promoter region of the HLA-DQA1 gene (-240 and -200 base pairs upstream) defines ten different QAP (DQA1-Promoter) alleles, which are associated with certain DQA1-alleles. The Y-Box in the DQA1 promoter (YC-Box -125 to -115 upstream from the ATG) differs from the consensus sequence (-123 A for G) of all other MHC class II Y-Boxes, resulting in a lower affinity to the NF-Y transcription factor and in a reduced expression of DQA1. A second substitution in the Y-Box of QAP 4.1 and 4.2 (-119 A for G) is found in the promoter alleles of the DQA1-alleles (DQA1*0401, *0501, *0601) and is strongly associated with susceptibility to EOPA-JCA.

Age of Onset↗
PubMed1998

Immunodominant major outer membrane proteins of Ehrlichia chaffeensis are encoded by a polymorphic multigene family.

Several immunodominant major proteins ranging from 23 to 30 kDa were identified in the outer membrane fractions of Ehrlichia chaffeensis and Ehrlichia canis. The N-terminal amino acid sequence of a 28-kDa protein of E. chaffeensis (one of the major proteins) was determined. The gene (p28), almost full length, encoding the 28-kDa protein was cloned by PCR with primers designed based on the N-terminal sequence of the E. chaffeensis 28-kDa protein and the consensus sequence between the C termini of the Cowdria ruminantium MAP-1 and Anaplasma marginale MSP-4 proteins. The p28 gene was overexpressed, and antibody to the recombinant protein was raised in a rabbit. The antibody and serum from a patient infected with E. chaffeensis reacted with the recombinant protein, three proteins (29, 28, and 25 kDa) of E. chaffeensis, and a 30-kDa protein of E. canis. Immunoelectron microscopy with the rabbit antibody revealed that the antigenic epitope of the 28-kDa protein was exposed on the surface of E. chaffeensis. Southern blot analysis with a 32P-labeled p28 gene probe revealed multiple copies of genes homologous to p28 in the E. chaffeensis genome. Six copies of the p28 gene were cloned and sequenced from the genomic DNA by using the same probe. The open reading frames of these gene copies were tandemly arranged with intergenic spaces. They were nonidentical genes and contained a semivariable region and three hypervariable regions in the predicted protein molecules. One of the gene copies encoded a protein with an internal amino acid sequence identical to the chemically determined N-terminal amino acid sequence of a 23-kDa protein of E. chaffeensis. Immunization with the recombinant P28 protein protected mice from infection with E. chaffeensis. These findings suggest that the 30-kDa-range proteins of E. chaffeensis represent a family of antigenically related homologous proteins encoded by a single gene family.

Amino Acid Sequence↗
PubMed1998

Cloning and characterization of multigenes encoding the immunodominant 30-kilodalton major outer membrane proteins of Ehrlichia canis and application of the recombinant protein for serodiagnosis.

A 30-kDa major outer membrane protein of Ehrlichia canis, the agent of canine ehrlichiosis, is the major antigen recognized by both naturally and experimentally infected dog sera. The protein cross-reacts with a serum against a recombinant 28-kDa protein (rP28), one of the outer membrane proteins of a gene (omp-1) family of Ehrlichia chaffeensis. Two DNA fragments of E. canis were amplified by PCR with two primer pairs based on the sequences of E. chaffeensis omp-1 genes, cloned, and sequenced. Each fragment contained a partial 30-kDa protein gene of E. canis. Genomic Southern blot analysis with the partial gene probes revealed the presence of multiple copies of these genes in the E. canis genome. Three copies of the entire gene (p30, p30-1, and p30a) were cloned and sequenced from the E. canis genomic DNA. The open reading frames of the two copies (p30 and p30-1) were tandemly arranged with an intergenic space. The three copies were similar but not identical and contained a semivariable region and three hypervariable regions in the protein molecules. The following genes homologous to three E. canis 30-kDa protein genes and the E. chaffeensis omp-1 family were identified in the closely related rickettsiae: wsp from Wolbachia sp. , p44 from the agent of human granulocytic ehrlichiosis, msp-2 and msp-4 from Anaplasma marginale, and map-1 from Cowdria ruminantium. Phylogenetic analysis among the three E. canis 30-kDa proteins and the major surface proteins of the rickettsiae revealed that these proteins are divided into four clusters and the two E. canis 30-kDa proteins are closely related but that the third 30-kDa protein is not. The p30 gene was expressed as a fusion protein, and the antibody to the recombinant protein (rP30) was raised in a mouse. The antibody reacted with rP30 and a 30-kDa protein of purified E. canis. Twenty-nine indirect fluorescent antibody (IFA)-positive dog plasma specimens strongly recognized the rP30 of E. canis. To evaluate whether the rP30 is a suitable antigen for serodiagnosis of canine ehrlichiosis, the immunoreactions between rP30 and the whole purified E. canis antigen were compared in the dot immunoblot assay. Dot reactions of both antigens with IFA-positive dog plasma specimens were clearly distinguishable by the naked eye from those with IFA-negative plasma specimens. By densitometry with a total of 42 IFA-positive and -negative plasma specimens, both antigens produced results similar in sensitivity and specificity. These findings suggest that the rP30 antigen provides a simple, consistent, and rapid serodiagnosis for canine ehrlichiosis. Cloning of multigenes encoding the 30-kDa major outer membrane proteins of E. canis will greatly facilitate understanding pathogenesis and immunologic study of canine ehrlichosis and provide a useful tool for phylogenetic analysis.

Amino Acid Sequence↗
PubMed2003

Identification of variations in SzP proteins of Streptococcus equi subspecies zooepidemicus and the relationship between protein variants and clinical signs of infection in horses.

OBJECTIVE: To determine whether previously unidentified variations of the SzP protein of Streptococcus equi subsp zooepidemicus were present in horses with various clinical signs of infection and whether any relationship could be identified between SzP protein variants and naturally occurring clinical conditions. SAMPLE POPULATION: 23 isolates of S equi subsp zooepidemicus were recovered from specimens of horses with various clinical conditions and used as a representative population of isolates for evaluation of different SzP protein variants. PROCEDURE: Genetic heterogeneity of the isolates was demonstrated by repetitive extragenic palindromic-polymerase chain reaction analysis. The SzP gene was sequenced and the presumed protein sequence determined for each isolate. Characteristics of the SzP proteins were compared among the isolates and in relation to the clinical conditions of horses from which they were recovered. RESULTS: The signal peptide types, number of proline-glutamic acid-proline-lysine repeats, and anchor sequences were consistent with those previously described for the SzP protein. Many of the isolates clustered with 5 previously described types on the basis of the hypervariable region of the SzP protein. One additional variant, which represented 8 of the isolates, was identified. Particular motifs in the hypervariable region accounted for many of the differences among hypervariable types. CONCLUSIONS AND CLINICAL RELEVANCE: The SzP protein appears to be limited to a selected number of types. Variations in the SzP protein are frequently determined on the basis of different motifs rather than random amino acid substitutions. There does not appear to be any association of SzP protein variations and clinical manifestations of infection in horses.

Abortion, Veterinary↗