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PubMed1985

The molecular structure of different polymorphic forms of canine C3 and C4.

The subunit composition of different electrophoretic forms of canine C3 and C4 was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of reduced immune precipitates. Canine C4 comprises alpha, beta, and gamma chains of approximate molecular weight 90 000-95 000, 72 000, and 33 000, respectively. The molecular weight of the alpha chain of the C4 1 allelic product was approximately 95 000, but 90 000 for the C4 2 and C4 4 allotypes. No differences were observed in the molecular weights of the beta or gamma chains of any canine C4 phenotype tested. Canine C3 appears to be encoded by a single locus. The subunit composition comprises an alpha and beta chain with molecular weights of approximately 106 000 and 71 000, respectively. Unlike C4, no differences in the molecular weights of the subunits were observed in different electrophoretic forms of canine C3.

Alleles↗
PubMedDate not supplied

[A definition of the nomenclature of allele variants and a description of allele polymorphism within a molecular-genetic individualization system based on the pentanucleotide tandem replication of HUMCD4].

While analyzing the available published data, we found significant differences in definition of alleles of the HUMCD4 polymorphic chromosome locus. It is an obstacle for comparing the expertise results obtained while using the locus as molecular individualization system in different laboratories and, as a consequence, it hinders the use of the said marker in building up a reference database. The structure of the HUMCD4 locus was analytically investigated and the distribution of the locus alleles was systemized in a sample of 407 persons (citizens of Russia who are not blood relatives) within the present case study for the purpose of a detailed definition of its allele's characteristics. We worked out recommendations related with the nomenclature standardization of alleles of the HIMCD4 locus and specified the main population features of the locus polymorphism on the bases of the studied sample of Russia's citizens. The results can be used as reference parameters in interpreting the findings of the molecular-genetic identification expertise and examinations and in building up databases.

Alleles↗
PubMed2001

Comparison of DNA sequencing of the protein A gene polymorphic region with other molecular typing techniques for typing two epidemiologically diverse collections of methicillin-resistant Staphylococcus aureus.

The aim of this study was to compare the recently developed typing approach for methicillin-resistant Staphylococcus aureus (MRSA) based on the DNA sequencing of the protein A gene polymorphic region (spaA typing) with a combination of three well-established molecular typing techniques: ClaI-mecA vicinity polymorphisms, ClaI-Tn554 insertion patterns, and SmaI pulsed-field gel electrophoresis (PFGE) profiles. In order to evaluate the applicability of this typing technique in different types of studies, two groups of MRSA clinical isolates were analyzed: a collection of 185 MRSA isolates circulating in Hungary recovered from 17 hospitals in seven cities during a 3-year period (1994 through 1996), and a selection of 53 MRSA strains isolated in a single hospital in Hungary between 1997 and 1998. The 238 MRSA clinical strains from Hungary were first classified in clonal types (defined as ClaI-mecA::ClaI-Tn554::SmaI-PFGE patterns), and 65 of the 238 strains, representing major MRSA clones and some sporadic clones, were further analyzed by spaA typing. Our results showed that the lineages most recently introduced in the hospital setting showed little variability in spaA types, whereas the MRSA clones circulating for a longer period of time and spread among several hospitals showed a higher degree of variability. The implementation of the spaA typing method was straightforward, and the results obtained were reproducible, unambiguous, and easily interpreted. This method seems to be adequate for outbreak investigations but should be complemented with other techniques in long-term surveillance or in studies comparing distant clonal lineages.

Amino Acid Sequence↗
PubMed2006

Kinetic insights into the role of the solvent in the polymorphism of 5-fluorouracil from molecular dynamics simulations.

We investigate the fundamental factors controlling polymorphism in 5-fluorouracil by performing molecular dynamics simulations of solutions of the compound in water, nitromethane, and wet nitromethane. Analysis of the effect of solvent on the initial aggregation of 5-fluorouracil molecules shows that the strong binding of water to the 5-fluorouracil molecule hinders the formation of the doubly hydrogen-bonded dimer and, by default, promotes close hydrophobic F...F interactions that are a feature of the unusual (Z' = 4) structure of form I. In contrast, doubly hydrogen-bonded dimers are observed to form readily in solution in dry nitromethane, consistent with the crystallization of the doubly hydrogen-bonded ribbon structure of form II from this solvent. When nitromethane is doped with water, the water forms hydrogen bonds to the solute, interfering with the formation of the doubly hydrogen-bonded dimers, which is consistent with the crystallization of form I from this hygroscopic solvent when it is not dried. Overall, the molecular dynamics simulations provide an atomistic picture of how solvent-solute interactions can significantly affect the initial association of 5-fluorouracil molecules to the extent that they determine the polymorphic outcome of the crystallization.

Antimetabolites, Antineoplastic↗
PubMed1985

Genetic analysis of human lymphocyte proteins by two-dimensional gel electrophoresis. VII. Genetic polymorphism of cytosol polypeptide with molecular weight of 38,000.

We describe a genetic polymorphism of cytosol polypeptide with mol. wt. of 38,000 detected in phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes by two-dimensional gel electrophoresis. Three different electrophoretic phenotypes (type 1-1, 2-1, 2-2) of the polypeptide have been identified in a Japanese population. Family and population studies indicate that three phenotypes are determined by two common alleles at a single autosomal locus. Since the polypeptide is mainly present in cytosol of cells, we propose that the polypeptide be temporarily designated as cytosol polypeptide with mol.wt. of 38,000 (CP38) and that the gene for CP38 be designated as CP38. The gene frequencies of two common alleles (CP38(1) and CP38(2)) are 0.899 and 0.101, respectively, in a Japanese population. The data on gel filtration of cytosol proteins on a Sephadex G-100 column suggest that CP38 exists as a dimer in the cytosol. CP38 was observed in the wide range of different cells, including B-lymphoblastoid cells, adult skin fibroblasts, HeLa cells, and erythrocytes. In 11 out of 72 individuals, the phenotypes of CP38 were different from those of adenosine deaminase which is similar to CP38 in subunit size, cell distribution, and allele frequencies. These data indicate that CP38 is a new polymorphic polypeptide encoded by an autosomal locus.

Alleles↗
PubMed2000

Alu elements and the human genome.

Alu insertional elements, the most abundant class of SINEs in humans are dimeric sequences approximately 300 bp in length derived from the 7SL RNA gene. These sequences contain a bipartite RNA pol III promoter, a central poly A tract, a 3' poly A tail, numerous CpG islands and are bracketed by short direct repeats. An estimated 500,000 to 1 x 10(6) units are dispersed throughout the human haploid genome primarily in AT rich neighborhoods located within larger GC dense chromosomal regions via a mechanism known as retroposition. Retroposition activity of Alu elements is determined by both internal and flanking regulatory elements as well as distant genes affecting transcription or transcript stability. Alu elements impact the organization and expression of the human genome at many levels including the processes of recombination, transcription and translation. Twelve subfamilies of Alu are defined by distinct patterns of diagnostic base substitutions. Subfamilies may be classified as young, intermediate or old reflecting the time since the start of retroposition by their members. Some insertions of the youngest subfamilies are not yet fixed in the human species and represent polymorphic loci. Alus are excellent molecular markers for a variety of reasons. They aid in tracing the complex pattern of duplication and rearrangements that occurred during the evolution of primate genome. Unlike other mutations, Alu sequences are rarely lost completely once retroposed, have a defined ancestral state and are free from homoplasy since independent and identical insertions are highly unlikely. Because of these characteristics, Alus are literally molecular fossils. Polymorphic Alu loci are especially useful in studies of human genetic diversity and in pedigree and forensic analysis.

Alu Elements↗
PubMed2002

Kainic acid induces leukemia inhibitory factor mRNA expression in the rat brain: differences in the time course of mRNA expression between the dentate gyrus and hippocampal CA1/CA3 subfields.

Leukemia inhibitory factor (LIF) is a pluripotent cytokine which affects the survival and differentiation of various types of cells both in the hematopoietic and nervous systems. In this study, the time course and localization of LIF mRNA expression following kainic acid-induced seizures were examined by northern blot analyses and in situ hybridization. Northern blot analyses demonstrated that intraperitoneal injection of kainic acid at a convulsive dose induced LIF mRNA expression intensely in the hippocampus and moderately to weakly in the cerebral cortex, thalamus and hypothalamus. The expression peaked at 8-24 h after the injection in the hippocampus and cerebral cortex and at 8 h in the thalamus and hypothalamus. In situ hybridization revealed different time courses of LIF mRNA expression depending on the area of the hippocampus; that is, the expression peaked at 10 h in the granule cell layer of the dentate gyrus, then at 12 h in the polymorph and molecular layers of the dentate gyrus, and finally at 12-24 h in the strata oriens and radiatum of the CA1 and CA3 subfields. It is worth noting that the expression of LIF mRNA was intense in the dentate gyrus, the region where neurogenesis and aberrant network reorganization have been shown to be induced by seizures. The upregulation of LIF mRNA expression in the dentate granule cell layer followed by that in the dentate polymorph and molecular layers may be involved in activity-dependent neurogenesis in the granule cell layer and ectopic migration of granule cells to the polymorph and molecular layers in the dentate gyrus.

Animals↗
PubMed1988

Mitochondrial DNA polymorphisms in Italy. II. Molecular analysis of new and rare morphs from Sardinia and Rome.

A molecular analysis of morphs found in a previous survey of mtDNA restriction enzyme polymorphisms in Italy revealed that different site changes can give similar patterns and that the same mutation can yield variant morphs for apparently unrelated enzymes. 1. Alternative site variations were found to yield restriction fragment patterns resembling HpaI morph 4, HaeII morph 5 and AvaII morph 2. 2. A strong association was observed between the BamHI morph 3 (gain of site a) and the AvaII morph 9 and its derivatives (loss of site d). This association appears to result from an A to G transition at base pair (bp) 13,368 which simultaneously creates a new BamHI site and abolishes an AvaII site. On the other hand, the loss of the AvaII site d, which in Italy was only found in the above-mentioned association, does not always produce a new BamHI site, as observed in other Caucasian groups. Similarly, the BamHI morph 2 (gain of site b) was always found to be associated with AvaII morphs lacking site f. An A to G transition at bp 16,391 was shown to account for both changes. As in the previous case, the converse is not true. Hence, these data show that AvaII sites d and f were lost in more than one way and one of these seems to be typical of Caucasians. 3. The variation producing BamHI-3/AvaII-9 and derivatives is preferentially associated with MspI morph 4 but this is not a product of a shared mutation. Hence, this association must be the result of the linkage disequilibrium due to the maternal inheritance of mtDNA and lack of recombination. 4. The high frequency of the combination BamHI-3/AvaII-9 and derivatives with MspI-4 found in Italy (29 subjects out of 229 analysed) can best be explained by diffusion of the relevant haplotype rather than by repeated mutational events. 5. The phylogeny trees of all mtDNA morphs so far described and of mtDNA types in Caucasians have been revised taking into account both the inter- and the intra-morph heterogeneity detected by this analysis.

Child↗
PubMed2001

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia.

Low folate intake as well as alterations in folate metabolism as a result of polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with an increased incidence of neural tube defects, vascular disease, and some cancers. Polymorphic variants of MTHFR lead to enhanced thymidine pools and better quality DNA synthesis that could afford some protection from the development of leukemias, particularly those with translocations. We now report associations of MTHFR polymorphisms in three subgroups of pediatric leukemias: infant lymphoblastic or myeloblastic leukemias with MLL rearrangements and childhood lymphoblastic leukemias with either TEL-AML1 fusions or hyperdiploid karyotypes. Pediatric leukemia patients (n = 253 total) and healthy newborn controls (n = 200) were genotyped for MTHFR polymorphisms at nucleotides 677 (C-->T) and 1,298 (A-->C). A significant association for carriers of C677T was demonstrated for leukemias with MLL translocations (MLL+, n = 37) when compared with controls [adjusted odd ratios (OR) = 0.36 with a 95% confidence interval (CI) of 0.15-0.85; P = 0.017]. This protective effect was not evident for A1298C alleles (OR = 1.14). In contrast, associations for A1298C homozygotes (CC; OR = 0.26 with a 95% CI of 0.07--0.81) and C677T homozygotes (TT; OR = 0.49 with a 95% CI of 0.20--1.17) were observed for hyperdiploid leukemias (n = 138). No significant associations were evident for either polymorphism with TEL-AML1+ leukemias (n = 78). These differences in allelic associations may point to discrete attributes of the two alleles in their ability to alter folate and one-carbon metabolite pools and impact after DNA synthesis and methylation pathways, but should be viewed cautiously pending larger follow-up studies. The data provide evidence that molecularly defined subgroups of pediatric leukemias have different etiologies and also suggest a role of folate in the development of childhood leukemia.

Adolescent↗
PubMed1995

Comparison of multilocus enzyme electrophoresis and random amplified polymorphic DNA analysis for molecular subtyping of Cryptococcus neoformans. The Cryplococcal Disease Active Surveillance Group.

We evaluated multilocus enzyme electrophoresis (MEE) and random amplified polymorphic DNA (RAPD) for their usefulness in subtyping 344 Cryptococcus neoformans clinical isolates obtained from four U.S. metropolitan areas in 1992 to 1994. MEE and RAPD with five primers both discriminated between the two varieties of C. neofromans. MEE divided C. neoformans var. neoformans isolates into 15 enzyme electrophoretic subtypes (ETs) arranged in three complexes. The predominant ET 1 complex contained 10 ETs, with isolates from 70% of patients in 1 ET. RAPD with five primers further sorted this predominant ET into 19 subtypes, with 60% of isolates sorting into three RAPD types. The ET 8 MEE complex, containing three ETs, could not be divided further by RAPD. The ET 7 complex (two ETs) included isolates from all serotype AD patients. Although both MEE and RAPD identified isolates of C. neoformans var. gattii, neither distinguished between serotypes B and C. These results showed that the two C. neoformans varieties could be identified by MEE or RAPD profile as well as by biochemical methods. RAPD improved the discriminatory power of MEE for isolates within the ET 1 complex but with other ETs offered little additional sensitivity over MEE and was less sensitive than MEE with isolates of C. neoformans var. gattii. This information will be useful in identifying particular environmental sources of disease-causing exposures, in seeking clusters of cases, and in determining whether an infecting strain changes over time.

Cryptococcus neoformans↗
PubMed2002

Familial dysalbuminemic hyperthyroxinemia: a rare example of albumin polymorphism and its rapid molecular diagnosis.

Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of euthyroid hyperthyroxinemia, although a rare example of albumin polymorphism. FDH is inherited in an autosomal dominant manner and is characterized by enhanced binding of thyroxine to a mutant form of albumin, probably at Site 1, subdomain 11A. Previous laboratory tests of FDH have been cumbersome, rarely available, and required demonstration of anti-albumin precipitable T4, isoelectric focusing of serum for albumin in presence of labeled T4 and, occasionally, comparison of the concentrations of metabolites of T4 that have different binding affinities to the abnormal albumin. Recent studies have shown that the same mutation in the albumin gene that results in FDH has been found in 13 unrelated families. A G-->A transition in codon 218 of the albumin gene resulted in the replacement of arginine with histidine. An intragenic Sac-1 polymorphic site was found in association with the specific FDH mutation, suggesting a founder effect. FDH in our Hispanic family was confirmed by isoelectric focusing of serum. Results of thyroid function tests in our affected patients were typical for the phenotype: high total T4 and normal total T3. Genomic DNA was amplified by PCR using a mismatched oligonucleotide primer that produced a unique restriction site (Dra III) only if the DNA sample contained the mutation in codon 218: CGC (Arg) to CAC (His). In affected individuals of this family expression of the FDH phenotype was associated with the presence of His218 in one of the two alleles. Analysis linking the FDH mutation to the Sac-1 polymorphism in this family was not informative. DNA analysis is a rapid and simple method to diagnose FDH in individuals with euthyroid hyperthyroxinemia.

Adolescent↗
PubMed2000

The molecular basis for genetic polymorphism of human deoxyribonuclease II (DNase II): a single nucleotide substitution in the promoter region of human DNase II changes the promoter activity.

Deoxyribonuclease II (DNase II) levels in human vary depending on whether the individual has the DNASE2*H (high) allele or the DNASE2*L (low) allele. We examined the promoter activity of the 5'-flanking region of each of these alleles by transient transfection luciferase assay. DNASE2*H had 5-fold higher promoter activity than DNASE2*L in human hepatoma HepG2 cell. Comparison of the nucleotide sequences of the proximal promoter regions revealed a G to A transition at position -75; G and A residues were assigned to DNASE2*H and *L, respectively. Since no differences were found between the open reading frame sequences of these alleles, it is likely that the A-75G transition causes the allelic difference in the promoter activity of the gene, underlying the genetic polymorphism.

Alleles↗
PubMed2001

Automated ribotyping and random amplified polymorphic DNA analysis for molecular typing of Salmonella enteritidis and Salmonella typhimurium strains isolated in Italy.

AIMS: The ability of automated ribotyping and random amplified polymorphic DNA (RAPD) analysis to differentiate Salmonella enteritidis and Salmonella typhimurium isolates in relation to their origin was evaluated. METHODS AND RESULTS: The restriction enzymes EcoRI, PvuII and PstI, and the random primers OPB17 and P1254, were tested for ribotyping and RAPD analysis, respectively. Seventeen subtypes were identified among the isolates of the two pathogenic Salmonella serovars using the RiboPrinter, and 25 subtypes using RAPD. CONCLUSIONS: The greatest degree of genetic diversity was observed among Salm. typhimurium isolates using both automated ribotyping (Simpson's index of discrimination 0878) and RAPD (Simpson's index of discrimination 0886). SIGNIFICANCE AND IMPACT OF THE STUDY: According to the results of this research, automated ribotyping and RAPD are two useful genotyping techniques for identifying unique and common subtypes associated with a specific source and location, and provide powerful tools for epidemiological investigations.

Animals↗
PubMed1986

Genetic analysis of human lymphocyte proteins by two-dimensional gel electrophoresis. VIII. Genetic polymorphism of cytosol polypeptide with molecular weight of 20,000.

We describe a genetic polymorphism of cytosol polypeptide with mol. wt. of 20,000 detected in lymphocytes and erythrocytes by two-dimensional gel electrophoresis. Three different electrophoretic phenotypes (type 1-1, 2-1, and 2-2) of the polypeptide have been identified in a Japanese population. Family studies indicate that the phenotypes are determined by two common alleles at a single autosomal locus. The polypeptide is present in the cytosol of various kinds of cells and is abundant in erythrocytes. The data on a gel filtration of the erythrocyte cytosol proteins on a Sephadex G-100 column suggest that the polypeptide exists as a dimer in cells. In nine out of 79 individuals, the phenotypes of the polypeptide were different from those of glyoxalase 1 (GLO1) which has similar properties in subunit size, cell distribution, and allele frequencies. These data indicate that the polypeptide with mol. wt. of 20,000 is a new polymorphic cellular polypeptide. We propose that the polypeptide be temporarily designated as cytosol polypeptide with mol. wt. of 20,000 (CP20) and that the gene for CP20 be designated as CP20. The gene frequencies of two common alleles (CP20(1) and CP20(2) are 0.955 and 0.045, respectively, in a Japanese population.

Blood Proteins↗
PubMed2006

Genome-wide investigation of intron length polymorphisms and their potential as molecular markers in rice (Oryza sativa L.).

Intron length polymorphisms (ILPs) have been used as genetic markers in some studies. However, a systematic investigation and large-scale exploitation of ILP markers has not been reported. In this study, we performed a genome-wide search of ILPs between two subspecies (indica and japonica) in rice using the draft genomic sequences of cultivars 93-11 (indica) and Nipponbare (japonica) and 32,127 full-length cDNA sequences of Nipponbare obtained from public databases. We identified 13,308 putative ILPs. Based on these putative ILPs, we developed 5811 candidate ILP markers via electronic-PCR with primers designed in flanking exons. We further conducted experiment to verify the candidate ILP markers. Out of 215 candidate ILP markers tested on 93-11, Nipponbare and their hybrid, we successfully exploited 173 codominant ILP markers. Further analyses on 10 rice accessions showed that these ILP markers were widely applicable and most (71.1%) exhibited subspecies specificity. This feature suggests that ILPs would be useful for the studies of genome evolution and inter-subspecies heterosis and for cross-subspecies marker-assisted selection in rice. In addition, by testing 51 pairs of the ILP primers on five Gramineae plants and three dicot plants, we found another desirable characteristic of rice ILP markers that they have high transferability to other plants.

Base Sequence↗
PubMed2000

The galU gene of Streptococcus pneumoniae that codes for a UDP-glucose pyrophosphorylase is highly polymorphic and suitable for molecular typing and phylogenetic studies.

The enzyme UTP-glucose-1-phosphate uridylyltransferase (UDP-glucose pyrophosphorylase, UDPG:PP) is synthesized by practically all organisms, although prokaryotic UDPG:PPs are evolutionarily unrelated to the eukaryotic counterparts. The primary structure of prokaryotic UDPG:PPs is well conserved, although little information exists on the polymorphism of the genes coding for these enzymes. It has been reported that the galU gene encoding the Streptococcus pneumoniae UDPG:PP is absolutely required for the synthesis of the capsular polysaccharide, a sine qua non prerequisite for virulence. A 594 bp fragment covering 66% of the galU gene from 37 pneumococcal isolates and the type strains of Streptococcus mitis, Streptococcus oralis, Streptococcus gordonii, Streptococcus sanguinis, Streptococcus salivarius, and Streptococcus sobrinus has been amplified by PCR and sequenced. Up to 21 different alleles were found in S. pneumoniae. They possess a mosaic-like structure and belong to, at least, two evolutionarily distinct families that show a sequence divergence of 15-20%. In spite of its marked polymorphism, phylogenetic relationships among pneumococcal strains deduced from the galU gene matched those previously established by using alternative approaches. Comparison of the pneumococcal galU alleles with those from other streptococci indicated the existence of a complex network of genetic interchange. The galU gene represents an informative marker to be used alone or in conjunction with other molecular typing methods.

Alleles↗
PubMed2001

A highly polymorphic degenerate microsatellite for molecular strain typing of Candida krusei.

Simple sequence repeats, due to their high variability, are widely used for molecular epidemiology of pathogenic micro-organisms. However, their usefulness is restricted by their high instability and low information content. Here, a locus, CKTNR, in the fungal pathogen Candida krusei is described which displays considerable sequence, as well as length, heterogeneity. Alleles of this locus, which contains a degenerate trinucleotide repeat, appear to be stable. The CKTNR polymorphism could serve as the basis for a molecular typing system of C. krusei. Furthermore, analysis of the CKTNR allele distribution suggested that C. krusei reproduces mainly clonally.

Candida↗