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At least 307 records · Page 17Linked to original sources
PubMed2002

Novel PLA2G4C polymorphism as a molecular diagnostic assay for 19q loss in human gliomas.

PLA2G4C, encoding cytosolic phospholipase A2-gamma (cPLA2-gamma), is a 17-exon gene located on chromosome 19q13.3 within the putative glioma tumor suppressor gene region. Given the clinical importance of assessing 1p and 19q loss in human gliomas, the development of convenient and practical assays for detecting allelic loss is of considerable priority in neuro-oncology. We report a minisatellite polymorphism in the untranslated region of exon 1, with allelic variants that have one, two or three 27-bp repeats. The polymorphism is informative in 55.7% of a reference population, and accurately detects allelic loss of 19q in human gliomas. This novel marker offers distinct advantages for assessing 19q status in malignant gliomas. The relatively large size of the repeats allows detection of allelic variants with standard ethidium bromide-stained agarose gels and the PLA2G4C marker is the closest polymorphism to the smallest common deletion area in the putative glioma tumor suppressor gene region. These characteristics suggest that the PLA2G4C polymorphism will be a convenient and practical assay for clinical and research evaluation of 19q status in human gliomas.

Alleles↗
PubMed1997

Molecular typing of Helicobacter pylori isolates from a multicenter U.S. clinical trial by ureC restriction fragment length polymorphism.

The molecular typing of 81 pretreatment Helicobacter pylori isolates and the comparison of 18 pretreatment-posttreatment pairs is described by restriction fragment length polymorphism (RFLP) of the ureC gene. The results of our study show the extreme genomic diversity of H. pylori and indicate that infection by H. pylori in the United States does not appear to be limited to a small number of RFLP types.

Anti-Bacterial Agents↗
PubMed2005

Cervical cancer and CYP2E1 polymorphisms: implications for molecular epidemiology.

INTRODUCTION: Besides human papillomavirus (HPV) infection, several cofactors are considered important for the development of cervical cancer (CC). Among these, tobacco smoke, other sexually transmitted diseases, inflammation and nutritional factors have been intensively described. CYP2E1 polymorphisms have been associated with the metabolization of several carcinogens, some of them considered risk factors for CC development, such as tobacco smoke. The aim of this study was to evaluate the role of CYP2E1 polymorphisms in the susceptibility to cervical cancer in a Portuguese population. PATIENTS AND METHODS: The genotypic analysis was performed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology, using peripheral blood samples of 454 individuals: 122 presented invasive squamous cell carcinoma (ICC), 59 presented squamous intraepithelial lesions (SIL), and the control population was composed of 274 healthy individuals. RESULTS: Concerning the DraI polymorphism, we observed a decreased risk for the development of squamous cervical lesions in the presence of the C allele [odds ratio (OR)=0.600; 0.378<OR<0.952; p=0.029]. In the stratification of the analysis according to the mean age, we observed an increased risk for the development of SIL, for women older than 39 years of age, in the presence of the D allele (OR=0.087; 0.012<OR<0.651; p=0.003). Regarding the RsaI polymorphism, we did not find any significant differences. CONCLUSION: The decreased risk observed for the development of SIL and not ICC in the presence of the D allele may indicate that CYP2E1 interferes with the initial steps of the carcinogenic process, probably due to its involvement in the action of immunological mediators, expressed during cervical inflammation. These aspects may help to define new therapeutic strategies for chemoprevention.

Adult↗
PubMed1998

Molecular analysis and polymorphism of the DLA-DQB genes.

Partial-length cDNA clones and full-length genomic clones corresponding to a complete canine DQB class II gene were isolated. Southern analyses suggested the presence of two DQB genes--one of which appeared to be a pseudogene lacking exon 2 called DQB2. The other DQB gene, called DQB1, was isolated from a genomic phage clone and contained six exons. The DQB1 clone was restriction mapped, and exon 2 was sequenced from 70 dogs. Twenty alleles were found. Most of the amino acid substitutions occurred at putative positions in the peptide binding site. Inheritance of these sequences showed Mendelian segregation with one or two alleles per dog. Cluster analysis of the nucleotide and predicted amino acid sequences subdivided the canine DQB1 alleles into four major allelic groups. The number of nonsynonymous changes was higher than the number of synonymous changes in the putative antigen recognition sites suggestive of positive selection.

Amino Acid Sequence↗
PubMedDate not supplied

Molecular cloning and polymorphism of the human immune deficiency virus type 2.

We recently reported the isolation of a novel retrovirus, the human immune deficiency virus type 2 (HIV-2, previously named LAV-2), from patients with acquired immune deficiency syndrome (AIDS) originating from West Africa. This virus is related to HIV-1, the causative agent of the AIDS epidemic now spreading in Central and East Africa, as well as the USA and Europe (see ref. 3 for review) both by its morphology and by its tropism and in vitro cytopathic effect on CD4 (T4) positive cell lines and lymphocytes. But preliminary hybridization experiments indicated that there are substantiated differences between the sequences of the two genomes. Furthermore, the proteins of HIV-1 and HIV-2 have different sizes and their serological cross-reactivity is restricted to the major core protein, as the envelope glycoproteins of HIV-2 are not immunoprecipitated by HIV-1-positive sera. We now report the molecular cloning of the complete 9.5-kilobase (kb) genome of HIV-2, the observation of restriction site polymorphism between different isolates, and a preliminary analysis of the relationship of HIV-2 with other human and simian retroviruses.

Base Sequence↗
PubMed1995

Polymorphic distribution and molecular diversification of mitochondrial plasmid-like DNAs in the genus Oryza.

Four kinds of circular plasmid-like DNA, designated B1, B2, B3 and B4, have been found in the mitochondria of rice (Oryza sativa L.). We analyzed the distribution of families of plasmid-like DNAs homologous to those of O. sativa in 40 strains of the genus Oryza with AA, BB, BBCC, CC, CCDD and EE genomes. Plasmid-like DNAs were observed only strains having AA, CC and CCDD genomes. The distribution patterns of strains with AA genome were highly polymorphic. We amplified the plasmid-like DNAs from strains with the AA genome by PCR and examined restriction fragments length polymorphisms (RFLPs). RFLPs were detected among families of plasmid-like DNA amplified from different strains. This result indicated that some mutations, such as base substitutions and the insertion or deletion of a small fragment of DNA, had occurred and had accumulated during the differentiation of strains with an AA genome.

Base Sequence↗
PubMed2004

Molecular characterization of Fusarium head blight resistance in Wangshuibai with simple sequence repeat and amplified fragment length polymorphism markers.

Molecular mapping of Fusarium head blight (FHB) resistance quantitative trait loci (QTL) and marker-assisted selection of these QTL will aid in the development of resistant cultivars. Most reported FHB resistance QTL are from 'Sumai 3' and its derivatives. 'Wangshuibai' is a FHB-resistant landrace that originated from China and is not known to be related to 'Sumai 3'. A mapping population of 139 F(5:6) recombinant inbred lines was developed from a cross of 'Wangshuibai' and 'Wheaton'. This population was developed to map the FHB-resistant QTL in 'Wangshuibai' and was evaluated twice for Type II FHB resistance. A total of 1196 simple sequence repeat and amplified fragment length polymorphism markers were screened on this population, and four FHB resistance QTL were detected. A major QTL near the end of 3BS explained 37.3% of the phenotypic variation. Another QTL on 3BS, located close to the centromere, explained 7.4% of the phenotypic variation. Two additional QTL on 7AL and 1BL explained 9.8% and 11.9% of the phenotypic variation, respectively. The simple sequence repeat and amplified fragment length polymorphism markers closely linked to these QTL may be useful for stacking QTL from 'Wangshuibai' and other sources to develop cultivars with transgressive FHB resistance.

China↗
PubMedDate not supplied

[Allele polymorphism of molecular-genetic individualizing systems based on tetranucleotide tandem repeats LPL, vWA and TH01 among the population of Russia].

Until recently, data bases on incidence rates of alleles STR (LPL, vWA and THO1 loci) have not been introduced in Russia. To obtain information on the above rates in Russia, a large scale research of distribution of LPL, vWA and Tho1 loci has been performed among a sample of 442 blood-unrelated persons from 57 regions of the Russian Federation to specify basic assessment characteristics of these loci and to raise efficiency of expert use of identifying systems on their base. Relevant parameters (allele frequencies) are presented for each polymorphic locus as well as basic population characteristics of polymorphism in the studied sample of RF population. These results can be used as key parameters for standard probability estimations in assessing the results of molecular-genetic identification.

Alleles↗
PubMed1994

Primary structure and molecular basis of polymorphic appearance of an acetyltransferase (AT-II)* in hamsters.

Three hamster clones (clones 1, 2 and 3) were isolated from a genomic library constructed from a homozygote rapid acetylator using a cDNA (hamAT-101) of a monomorphic acetyltransferase (AT-I) as a probe. Clone 1 (13 kbp) was found to contain a gene corresponding to AT-I. The entire coding region was located in an exon and completely identical to that of AT-I cDNA. Clones 2 and 3 (14.5 and 15 kbp) each contained identical information to the AT-I-related protein (AT-B protein). The intronless coding region shared 83.7% of sequence similarly to the AT-I cDNA, and its length was identical to that of the AT-I cDNA. Clone 2 also included a nucleotide sequence identical to the 3'-portion of the AT-I gene, which is located 5'-upstream of the AT-B gene. Restricted fragment lengths of clone 3, which encompassed the entire coding region was expressed in COS-1 cells. The expressed protein migrated at a position identical to that of AT-II purified from a hamster liver on Western blots. AT-B-expressed protein catalysed acetyl CoA-dependent N-acetylation of 2-aminofluorene and p-aminobenzoic acid, but had marginal activities for O-acetylation of 2-N-hydroxyamino-6-methyl-6-methyldipyrido[1,2-a:3',2'-d]imidazole and N-hydroxyarylacetamide-dependent N-acetylation of 4-aminoazobenzene. These results are in good agreement with the data of AT-II purified from hamster livers, indicating that the AT-B gene encodes a polymorphic acetyltransferase (AT-II) in hamsters. Although the AT-II protein was undetectable in slow acetylators, specific mRNA, hybridizing with a selective oligonucleotide probe for the AT-II gene (AT-B), was detected in livers of both homozygous acetylators. Analysis of genomic DNA of a homozygous slow phenotype hamster indicates that AT-II DNA from the slow phenotype has a point mutation which causes premature termination at the 243th (Arg to stop codon) position of the deduced amino acid sequence. PCR-RFLP analysis further confirmed that the point mutation conferred a defective AT-II protein in slow phenotype hamsters.

4-Aminobenzoic Acid↗
PubMed1990

The genetic polymorphism of debrisoquine/sparteine metabolism-molecular mechanisms.

The genetic polymorphism of debrisoquine/sparteine metabolism is one of the best studied examples of a genetic variability in drug response. 5-10% of individuals in Caucasian populations are 'poor metabolizers' of debrisoquine, sparteine and over 20 other drugs. The discovery and the inheritance of deficient debrisoquine/sparteine metabolism are briefly described, followed by a detailed account of the studies leading to the characterization of the deficient reaction and the purification of cytochrome P-450IID1, the target enzyme of this polymorphism. It is demonstrated by immunological methods that deficient debrisoquine hydroxylation is due to the absence of P-450IID1 protein in the livers of poor metabolizers. The cloning and sequencing of the P-450IID1 cDNA and of IID1 related genes are summarized. The P-450IID1 cDNA has subsequently led to the discovery of aberrant splicing of P-450IID1 pre-mRNA as the cause of absent P-450IID1 protein. Finally, the identification of mutant alleles of the P-450IID1 gene (CYP 2D) by restriction fragment length polymorphisms in lymphocyte DNA of poor metabolizers is presented.

Debrisoquin↗
PubMed1994

Molecular analysis of polymorphic loci to study chimerism after allogeneic bone marrow transplantation. Heteroduplex analysis in denaturing gradient gel electrophoresis: a new approach to detecting residual host cells.

Since both donor/recipient origin of hematopoietic cells and the proportion of residual host cells influence the outcome of BMT, we performed this study to design a rapid and efficient strategy for chimerism analysis. Using the polymerase chain reaction, we analyzed the informativity and sensitivity of two kinds of polymorphism in 35 HLA-identical sibling pairs: four variable number of tandem repeats (VNTR) systems and the frameworks (FW) of the beta-globin gene. The latter polymorphisms were analyzed by means of denaturing gradient gel electrophoresis, a method that identifies heterozygosity by the presence of heteroduplexes. All the siblings were found to be informative for at least one polymorphic system. In addition, 34 of the 35 sibling pairs (97%) bore at least one VNTR or FW system which permitted the detection of the minor population (i.e., the first sibling's DNA contained an allele that was absent from the second sibling's DNA). The VNTR- and FW-based methods were highly sensitive, being able to reveal minor populations representing as little as 1% and 5% of total DNA, respectively. The value of the beta-globin gene FW analysis lies in the detection of additional heteroduplexes, which reflect genotypic differences between siblings' DNA. We describe the experimental conditions required to detect the minor DNA population in virtually all cases. As direct evidence of mixed chimerism can be obtained from denaturing gradient gel electrophoresis analysis of any highly informative polymorphic system, this method can be applied to chimerism analysis.

Base Sequence↗
PubMed1993

Molecular cloning of polymorphic markers on RLGS gel using the spot target cloning method.

A new method for target cloning of DNA fragments corresponding to spots on the two-dimensional restriction landmark genomic scanning (RLGS) profile has been developed (targeted spot cloning). We used a Not I restriction trapper to select target DNA fragments from Not I, Eco RV double digests of genomic DNA. The use of the restriction trapper substantially reduces the background clones that are established from the direct recovery of RLGS spot DNA from the two-dimensional gels. Genomic DNA clones were isolated in this study as mouse genome markers for 58 spot loci that were previously characterized using RLGS spot mapping. This method provides a powerful tool for isolating DNA clones after their identification by RLGS system.

Animals↗
PubMed2006

Molecular mechanism for the cross-nucleation between polymorphs.

We use molecular simulations to study the early stages of crystallization in a supercooled liquid of Lennard-Jones particles. We observe the onset of concomitant polymorphism and demonstrate that this phenomenon results from the cross-nucleation of a metastable polymorph on the stable polymorph. We also show that cross-nucleation is selective as it only takes place between polymorphs of almost equivalent free energy. Our simulations provide detailed insights into the molecular mechanism underlying concomitant polymorphism and cross-nucleation between polymorphs.

Journal Article↗
PubMed2004

Multiple polymorphic loci for molecular typing of strains of Mycobacterium leprae.

The need for molecular tools for the differentiation of isolates of Mycobacterium leprae, the organism that causes leprosy, is urgent in view of the continuing high levels of new case detection, despite years of aggressive chemotherapy and the consequent reduction in the prevalence of leprosy. The slow onset of leprosy and the reliance on physical examination for detection of disease have restricted the epidemiological tracking necessary to understand and control transmission. Two genetic loci in several isolates of M. leprae have previously been demonstrated to contain variable-number tandem repeats (VNTRs). On the basis of these reports and the availability of the full genome sequence, multiple-locus VNTR analysis for strain typing has been undertaken. A panel of 11 short tandem repeat (STR) loci with repeat units of 1, 2, 3, 6, 12, 18, 21, and 27 bp from four clinical isolates of M. leprae propagated in armadillo hosts were screened by PCR. Fragment length polymorphisms were detected at 9 of the 11 loci by agarose gel electrophoresis. Sequencing of representative DNA products confirmed the presence of VNTRs between isolates. The application of nine new polymorphic STRs in conjunction with automated methods for electrophoresis and size determination allows greater discrimination between isolates of M. leprae and enhances the potential of this technique to track the transmission of leprosy.

Animals↗
PubMed1986

Molecular structure and polymorphic map of the human phenylalanine hydroxylase gene.

Human phenylalanine hydroxylase is a liver-specific enzyme that catalyzes the conversion of phenylalanine to tyrosine. Absence of enzymatic activity results in phenylketonuria, a genetic disorder that causes development of severe mental retardation in untreated children. In this paper we report the cloning and structure of the normal human phenylalanine hydroxylase gene, which was isolated in four overlapping cosmid clones that span more than 125 kilobases (kb) of the genetic locus. The peptide coding region of the gene is about 90 kb in length and contains 13 exons, with intron sizes ranging from 1 to 23 kb. Exons at the 3' half of the gene are compact, whereas those at the 5' half are separated by large introns. The human phenylalanine hydroxylase gene codes for a mature messenger RNA of approximately 2.4 kb, and its noncoding to coding DNA ratio is one of the highest among eukaryotic genes characterized to date. The map positions of nine polymorphic restriction sites identified within the locus were established by restriction enzyme mapping of the cloned gene fragments. Two clusters of polymorphic sites were demonstrated: (1) BglII, PvuII(a), and PvuII(b) at the 5' end of the gene and (2) EcoRI, XmnI, MspI(a), MspI(b), EcoRV, and HindIII at the 3' end. The polymorphic site distribution within this gene is a useful tool for prenatal diagnosis and carrier detection of the genetic disorder, while knowledge of normal gene structure is a prerequisite for future characterization of mutant alleles.

Base Sequence↗