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At least 307 records · Page 17Linked to original sources

PubMed1998

Point mutation of a rubella virus E1 protein T-cell epitope by substitution of single amino acid reversed the restrictive HLA-DR polymorphism: a possible mechanism maintaining HLA polymorphism.

The influence of single amino acid substitutions within a rubella E1 protein T-cell epitope, E1(273-284) on T-cell recognition was studied. Substitutions of an uncharged amino acid A for an E or for a T and substitution of a T for S were found to not significantly reduce the T-cell responses. However, substitution of a charged residue such as E for hydrophobic residues (I, V, or W); D for Q; or a relatively larger size amino acid for polar residues completely abolished the cytotoxicities mediated by E1(273-284)-specific T-cell clone. A set of single amino acid-substituted peptide analogs of E1(273-284) not eliciting cytotoxicity of the T-cell clone was used to test the influence of point mutation of the epitope on HLA DR restrictions. A panel of B-cell lines with different DR4 subtypes was used as targets in cytotoxicity assays to determine the restrictive HLA molecules. Results showed that modification of the T-cell epitope by point mutation could reverse the HLA DR restriction from one allele to other alleles. A model based on these results has been proposed to explain the mechanism balancing major histocompatibility complex (MHC) polymorphism in outbred populations.

Amino Acid Substitution↗

PubMed2000

Toward a physical map of Drosophila buzzatii. Use of randomly amplified polymorphic dna polymorphisms and sequence-tagged site landmarks.

We present a physical map based on RAPD polymorphic fragments and sequence-tagged sites (STSs) for the repleta group species Drosophila buzzatii. One hundred forty-four RAPD markers have been used as probes for in situ hybridization to the polytene chromosomes, and positive results allowing the precise localization of 108 RAPDs were obtained. Of these, 73 behave as effectively unique markers for physical map construction, and in 9 additional cases the probes gave two hybridization signals, each on a different chromosome. Most markers (68%) are located on chromosomes 2 and 4, which partially agree with previous estimates on the distribution of genetic variation over chromosomes. One RAPD maps close to the proximal breakpoint of inversion 2z(3) but is not included within the inverted fragment. However, it was possible to conclude from this RAPD that the distal breakpoint of 2z(3) had previously been wrongly assigned. A total of 39 cytologically mapped RAPDs were converted to STSs and yielded an aggregate sequence of 28,431 bp. Thirty-six RAPDs (25%) did not produce any detectable hybridization signal, and we obtained the DNA sequence from three of them. Further prospects toward obtaining a more developed genetic map than the one currently available for D. buzzatii are discussed.

Amino Acid Sequence↗

PubMed1989

Polymorphism of the human T cell receptor alpha chain variable genes: identification of a highly polymorphic V gene probe.

In this study, we report the RFLP of the human T cell receptor (TCR) alpha chain variable gene segments. Using DNA samples from 20 individuals and three restriction endonucleases (BamHI, EcoRI and HindIII), the degree of RFLP of a number of different V gene segments was defined. Half of the V alpha subfamilies (6/12) were characterized by a predominant hybridization pattern, with only a few individuals displaying a second pattern. However, one particular V gene family, V alpha 6, has at least five allelic forms that segregated consistently in familial studies. The V alpha polymorphisms revealed in this study, together with those exhibited by V beta gene subfamilies, should prove useful in studying possible associations between TCR gene usage and disorders of the immune system.

Alleles↗

PubMed1995

Isoenzyme, restriction fragment length polymorphism, and random amplified polymorphic DNA characterization of Phaffia rhodozyma Miller et al.

The validity of the species concept was examined with strains of Phaffia rhodozyma by comparing the isoenzyme profiles, ribosomal DNAs, and random amplified polymorphic DNA (RAPD) patterns of the strains. The isoenzyme profiles appeared to be more stable than the RAPD patterns or the electrophoretic karyotypes determined previously (A. Nagy, N. Garamszegi, C. Vágvölgyi, and L. Ferenczy, FEMS Microbiol. Lett., in press). The ribosomal DNA patterns revealed only a limited degree of variability, while RAPD analysis proved to be the most useful method for differentiating the strains studied. Strain CBS 5905T (T = type strain) produced characteristic RAPD patterns, which were different from those produced by the other strains. However, despite the high degree of variability observed, the isoenzyme data and the slightly variable ribosomal DNA hybridization profiles confirmed that the strains which we examined belong to one species.

Base Sequence↗

PubMed2002

Neighboring-nucleotide effects on single nucleotide polymorphisms: a study of 2.6 million polymorphisms across the human genome.

We investigated substitution patterns and neighboring-nucleotide effects for 2,576,903 single nucleotide polymorphisms (SNPs) publicly available through the National Center for Biotechnology Information (NCBI). The proportions of substitutions were A/G, 32.77%; C/T, 32.81%; A/C, 8.98%; G/T, 9.06%; A/T, 7.46%; and C/G, 8.92%. The two nucleotides immediately neighboring the variable site showed major deviation from genome-wide and chromosome-specific expectations, although lesser biases extended as far as 200 bp. On the 5' side, the biases for A, C, G, and T were 1.43%, 4.91%, -1.70%, and -4.62%, respectively. These biases were -4.44%, -1.59%, 5.05%, and 0.99%, respectively, on the 3' side. The neighboring-nucleotide patterns for transitions were dominated by the hypermutability effects of CpG dinucleotides. Transitions were more common than transversions, and the probability of a transversion increased with increasing A + T content at the two adjacent sites. Neighboring-nucleotide biases were not consistent among chromosomes, with Chromosomes 19 and 22 standing out as different from the others. These data provide genome-wide information about the effects of neighboring nucleotides on mutational and evolutionary processes giving rise to contemporary patterns of nucleotide occurrence surrounding SNPs.

Base Composition↗

PubMed1995

Metastable single-strand DNA conformational polymorphism analysis results in enhanced polymorphism detection.

Single-strand DNA conformational polymorphism (SSCP) makes use of sequence-dependent folding of single-stranded DNA (ssDNA), which alters the electrophoretic mobility of the fragments, to detect sequence differences between closely related molecules. In this study ssDNAs were purified by depletion of the complementary strand and PCR reactants on magnetic M-280-strepavidin beads. It was found that SSCP profiles created by purified ssDNAs differ from the profiles created by more usual SSCP methods. Under some conditions, SSCP profiles using whole PCR reaction products may result from the interaction between residual PCR primers and ssDNAs. We observed that the ratio of conformers revealed by band position and band intensity may vary between the assay techniques and misinterpretation of sequence variants may result. Another observation of this study was the formation of metastable conformational isomers with bead-purified ssDNAs by eliminating the thermal treatment used in conventional SSCP methods. The metastable SSCP (mSSCP) represents a novel and sensitive system for detection of sequence variation between closely related DNAs. The technique used here for the preparation of the purified ssDNAs is potentially useful for automated PCR-SSCP analysis using capillary electrophoresis or other methods.

Autoradiography↗

PubMed1992

Distribution of polymorphic HLA-DR and -DQ alleles as determined by restriction fragment length polymorphism analysis in an Austrian population.

The restriction fragment length polymorphism (RFLP) of HLA-DR beta, -DQ alpha and -DQ beta genes was analyzed in 637 unrelated individuals from the Austrian population. The restriction enzyme was Taq I, and three exon-specific probes were applied. The gene frequencies, the Hardy-Weinberg equilibrium in DR beta and DQ loci, linkage disequilibria between the loci and haplotype frequencies are calculated. Rare associations between DR and DQ loci are described. Two RFLP patterns are demonstrated which were unique in the overall 1,000 individuals tested so far.

Alleles↗

PubMed1977

Frequency of RFA colour polymorphisms of human acrocentric chromosomes in caucasians: interrelationship with QFQ polymorphisms.

One hundred normal caucasians were studied by sequential QFQ and RFA in order to estimate the type and frequency of variation. Colour variants were classified into 1 of 6 colours by RFA and intensity variations into 1 of 5 levels by QFQ. The interrelationship between QFQ and RFA variants was also examined. It was found that there was no consistent relationship between negative or brilliant QFQ variants and the various colours observed with RFA. RFA colour polymorphisms for chromosomes 13, 14, 15, 21 and 22 were 33.0, 38.0, 28.0, 50.0 and 24.5% while QFQ frequencies were 56.5, 10.0, 10.0, 15.5 and 10.0% respectively. RFA is especially useful in studying the inheritance of chromosome 21.

Adult↗

PubMed2002

Polymorphisms in the ABCC2 (cMOAT/MRP2) gene found in 72 established cell lines derived from Japanese individuals: an association between single nucleotide polymorphisms in the 5'-untranslated region and exon 28.

We found nucleotide variability in the 5'-upstream region and exonic sequences of a gene-encoding canalicular multispecific organic anion transporter/multidrug resistance-associated protein 2 (cMOAT/MRP2) by polymerase chain reaction-based sequencing using genomic DNA from 72 established cell lines derived from 72 Japanese individuals. Four single nucleotide polymorphisms (SNPs) were found in the 5'-untranslational region and 21 in the exonic regions. Of them, 14 were nonsynonymous SNPs. One deletion of seven consecutive adenines resulting in a frameshift variant was also found. Four SNPs, c-24t, g1249a (V417I), c2366t (S789F), and c3972t (I1324I), were the same as those recently reported. A strong association was found between c-24t (5'-untranslated region) and c3972t (exon 28), with the promoter activity of the former worth being compared.

5' Untranslated Regions↗

PubMed2002

gyrA polymorphism in Campylobacter jejuni: detection of gyrA mutations in 162 C. jejuni isolates by single-strand conformation polymorphism and DNA sequencing.

Mutations in the quinolone resistance-determining region of the gyrA gene from 138 ciprofloxacin-resistant (MIC, > or =4 microg/ml) and 24 ciprofloxacin-susceptible (MIC, < or =1 microg/ml) clinical Campylobacter jejuni isolates were subjected to single-strand conformation polymorphism analysis and sequencing. All of the isolates could be assigned to three genotypic clusters based on silent mutations. All resistant isolates had a point mutation at codon 86.

Anti-Infective Agents↗

PubMed2002

Detection of MDR1 single nucleotide polymorphisms C3435T and G2677T using real-time polymerase chain reaction: MDR1 single nucleotide polymorphism genotyping assay.

The objective of this study was to develop a real-time polymerase chain reaction (PCR) method to detect MDR1 (human multidrug resistance gene) single nucleotide polymorphisms (SNPs) C3435T and G2677T. C3435T and G2677T are linked to MDR1*2, which is associated with enhanced efflux activity in vitro. Using the Smart Cycler, an allele-specific real-time PCR-based genotyping method was developed to detect C3435T and G2677T. The MDR1 genotype of human genomic DNA templates was determined by direct DNA sequencing. PCR reactions for genotyping C3435T and G2677T by using allele-specific primers were conducted in separate tubes. An additional nucleotide mismatch at the third position from the 3' end of each allele-specific primer was used to abrogate nonspecific PCR amplification. The fluorescence emitted by SYBR Green I was monitored to detect formation of specific PCR products. PCR growth curves exceeding the threshold cycle were considered positive. Fluorescence melt-curve analysis was used to corroborate results from PCR growth curves. Using PCR growth curves, our assay accurately determined hetero- and homozygosity for C3435T and G2677T. Genotype assignments based on PCR growth curve, melt-curve analysis, agarose gel electrophoresis, and direct DNA sequencing results of PCR products were in perfect agreement. We have developed a rapid MDR1 genotyping method that can be used to assess the contribution of MDR1*2 to pharmacokinetic and pharmacodynamic variability of P-glycoprotein substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Systematic search for single nucleotide polymorphisms in the resistin gene: the absence of evidence for the association of three identified single nucleotide polymorphisms with Japanese type 2 diabetes.

Resistin is a novel polypeptide specifically secreted from adipocytes, and its serum levels are increased in obese diabetic mice. Resistin antagonizes insulin and could account for insulin resistance. To determine whether there are single nucleotide polymorphisms (SNPs) in the resistin gene associated with type 2 diabetes, sequences for 24 Japanese type 2 diabetic patients were initially analyzed using PCR direct sequencing. Three SNPs were found in the introns, but none were present in the coding regions. The allele frequencies of genomic -167C>T, +157C>T, and +299G>A in 99 Japanese control subjects were determined to be 3.5, 6.6, and 39.4%, respectively. In each pair of these SNPs, linkage disequilibria were found between either -167C>T and +299G>A or +157C>T and +299G>A. A linkage disequilibrium was also detected among -167C>T, +157C>T, and +299G>A, and only four of the eight possible haplotypes defined by these SNPs were found. A comparison of the frequencies of these SNPs and haplotypes between 99 type 2 diabetes and 99 control subjects revealed no evidence for any association. These identified SNPs, which were in linkage disequilibrium, represent potentially useful tools for searching for their association with specific phenotypes of diabetes.

Adult↗

PubMed1992

Use of genetic polymorphisms detected by the random-amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) for differentiation and identification of Aedes aegypti subspecies and populations.

Amplification of random regions of genomic DNA using 10-base primers in the random-amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) was used to differentiate and identify mosquito populations based on genetic variation. Genomic DNA was extracted from individual mosquitoes from 11 geographic populations of Aedes aegypti and amplified in PCR reactions using single primers of arbitrary nucleotide sequence. Discriminant analysis of the population frequencies of RAPD fragments produced using three different primers allowed accurate discrimination between the geographic populations in 89% of individuals and between subspecies (Ae. aegypti aegypti versus Ae. aegypti formosus) in 100% of mosquitoes tested. The genetic relatedness of the populations was estimated using three different statistical methods, and unknown populations were correctly classified in a blind test. These results indicate that the RAPD-PCR technique will be useful in studies of arthropod molecular taxonomy and in epidemiologic studies of the relatedness of geographic populations and vector movement.

Aedes↗

PubMed2002

Detection of a primer-binding site polymorphism for the STR locus D16S539 using the Powerplex 1.1 system and validation of a degenerate primer to correct for the polymorphism.

Quality assurance samples submitted from the NCSBI as part of a contract with TBTG to outsource DNA Database samples showed unexpected discrepancies for the locus D16S539 when all other loci yielded identical results. Discrepancies observed included allele drop out and an imbalance in sister alleles with samples returned from TBTG. This led to a comprehensive review of the technical procedures used between the two laboratories to determine the cause of the discrepancies noted for the locus D16S539, since both laboratories were using the PowerPlex 1.1 typing kit from the Promega Corporation. The NCSBI and the TBTG utilize different extraction methods (organic extraction vs. FTA) and amplification conditions (AmpliTaq vs AmpliTaq Gold), respectively, so the exact cause of discrepancy observed was not immediately apparent. Experiments at the NCSBI associated the observed allele drop out and the imbalance of the sister alleles with the use of AmpliTaq Gold and a hot start procedure. Sequencing data revealed that a point mutation resides on the D16S539 primer-binding site that reaches polymorphic levels in African-American populations. This led to the development of a degenerate primer by the Promega Corporation to detect "missing" alleles when AmpliTaq Gold is used. The degenerate primer was then thoroughly tested to show its efficacy in detecting the "true" D16S539 profile when used.

Allelic Imbalance↗

PubMed1992

[DNA polymorphism in the Russian population. Analysis of dna restriction fragment length polymorphism in seven loci of the nuclear genome].

Using the method for polymerase chain reaction the polymorphism of eight markers of the nuclear DNA was studied. In a sample of Russians taken at random (N = 118) from predominantly southern and central regions of Russia, allele frequencies were determined for restriction sites HindIII at HBG-2 and PAH loci, AvaII at the HBB locus, MspI at the ApoB locus, PstI at D7S8, HincII at LDLR, TaqI and BamHI at the DSX164. Comparative data for different world regions are presented.

Chromosome Mapping↗

PubMed1978

[Physiological polymorphism of a population of the common frog. II. The polymorphism of the type of muscle tissue heat resistance in stress].

A study was made of the dynamics in the heat resistance of m. interphalangealis of individual grass frogs under stress. The response of muscle tissue to injury can be differentiated into three types according to the initial heat resistance level: increase, decrease and phase change of the resistance. The pattern of response of muscle tissue of individual frogs to stress is one of manifestationss of physiological polymorphism of the population.

Animals↗

PubMed1991

Membrane cofactor protein of the complement system. A HindIII restriction fragment length polymorphism that correlates with the expression polymorphism.

An RFLP was found in the DNA of 25 unrelated persons, two families, and five cell lines that correlated with their membrane cofactor protein phenotype. If restricted with HindIII, DNA derived from upper band predominant protein (U) phenotypes had a band at 2 kb, whereas DNA of lower band predominant (L) phenotypes had a 4-kb band. The equal band protein phenotype, in which equal quantities of the two species are expressed, had bands at both 4 and 2 kb. The polymorphic HindIII site was localized to an intron within the membrane cofactor protein gene between exon 1 (codes for 5'UT/signal peptide) and exon 2 (codes for the first short consensus repeat). Using the polymerase chain reaction (PCR), sequences around this site were amplified and a single band of 260 bp was produced. In the U phenotype, the PCR product was restricted with HindIII into 200- and 60-bp fragments. In the L phenotype, there was no change in the size of 260 bp upon restriction with HindIII. For the equal band protein phenotype, the PCR product was partially cleaved. The 260-bp PCR product was subcloned and sequenced. DNA from the U phenotype demonstrated an intact HindIII site (AAGCTT), whereas in the DNA of the L phenotype, this site was altered because a "G" was substituted for a "C" (AAGGTT).

Alleles↗

PubMed1991

Debrisoquine polymorphism: novel CYP2D6 gene Bam HI restriction fragment length polymorphism in the Ngawbé Guaymí Indian of Panama.

Markedly decreased cytochrome P450-mediated metabolism of debrisoquine, sparteine, and more than two dozen additional commonly prescribed drugs is an autosomal recessive trait that has been associated with several RFLP patterns involving the CYP2D6 gene. In Caucasians there are at least six variant alleles known to be correlated with the 'poor metabolizer' (PM) phenotype. We examined debrisoquine and sparteine metabolism and CYP2D6 RFLP patterns in 22 Ngawbé Guaymí Indians of Panama. We studied a two-generation family, a three-generation family, and three other unrelated PM individuals. Digestion of all 22 DNA samples with Xba I or Hind III did not produce the same varying CYP2D6 RFLP patterns as those commonly seen in at least two-thirds of all Northern European Caucasians and Chinese so far screened. In contrast, we found a single heretofore undescribed Bam HI polymorphism that was correlated with the PM phenotype among all Ngawbé Guaymí individuals examined. It is possible that this novel RFLP might represent a recent founder effect that has occurred in this unadmixed Amerindian tribe within the past 20,000-30,000 years.

Alleles↗