SEARCH · PubMed Health

Results for “Molecular polymorphism”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 199 records · Page 11Linked to original sources

PubMed1989

Complexity of MAM-6, an epithelial sialomucin associated with carcinomas.

The complexity of epithelial sialomucins was investigated by immunoprecipitation and membrane immunofluorescence, using monoclonal antibodies (MAbs) against MAM-6 and other sialomucins. MAbs against MAM-6 immunoprecipitated from a variety of sources either one or two sialylated glycoproteins with apparent molecular weights of over 400,000 under reducing as well as nonreducing conditions. The electrophoretic mobility of each MAM-6 glycoprotein as isolated from serum, milk, and cell lines of different individuals showed considerable variation. The differences in molecular weight of the MAM-6 glycoproteins were also reflected at the level of MAM-6 precursors which are less heavily glycosylated. Therefore, large differences in apparent molecular weight (150,000 and over) are most likely due to a variable protein backbone. We used this molecular polymorphism to prove that 11 MAbs against different sialomucins, obtained from various investigators, precipitated sialomucins generated from common precursor molecules. The pattern of reactivity of the MAbs with carcinoma cell lines was complex. All but the two MAbs, directed against putative carbohydrate epitopes, immunoprecipitated the precursor molecule from each cell line. However, some of them were unable to immunoprecipitate the mature form of MAM-6 from these cell lines. These results indicate that those epitopes are masked, probably due to cell line- or possibly cell type-dependent variations in glycosylation of the epithelial sialomucin. Even within a single cell line mature molecules with different epitopes were observed. The differential reactivity of the MAbs was confirmed by membrane immunofluorescence. These results show that MAM-6 belongs to a family of epithelial sialomucins with a polymorphic protein backbone and extensive variation in glycosylation.

Antibodies, Monoclonal↗

PubMed1999

Molecular determinants of the physicochemical properties of a critical prion protein region comprising residues 106-126.

Prion diseases are marked by the cerebral accumulation of conformationally modified forms of the cellular prion protein (PrP(C)), known as PrP(res). The region comprising the residues 106-126 of human PrP seems to have a key role in this conformational conversion, because a synthetic peptide homologous with this sequence (PrP106-126) adopts different secondary structures in different environments. To investigate the molecular determinants of the physicochemical characteristics of PrP106-126, we synthesized a series of analogues including PrP106-126 H(D), PrP106-126 A and PrP106-126 K, with l-His-->d-His, His-->Ala and His-->Lys substitutions respectively at position 111, PrP106-126 NH(2) with amidation of the C-terminus, PrP106-126 V with an Ala-->Val substition at position 117, and PrP106-126 VNH(2) with an Ala-->Val substitution at position 117 and amidation of the C-terminus. The analysis of the secondary structure and aggregation properties of PrP106-126 and its analogues showed the following. (1) His(111) is central to the conformational changes of PrP peptides. (2) Amidation of the C-terminal Gly(126) yields a predominantly random coil structure, abolishes the molecular polymorphism and decreases the propensity of PrP106-126 to generate amyloid fibrils. (3) PrP106-126 V, carrying an Ala-->Val substitution at position 117, does not demonstrate a fibrillogenic ability superior to that of PrP106-126. However, the presence of Val at position 117 increases the aggregation properties of the amidated peptide. (4) Amyloid fibrils are not required for neurotoxicity because the effects of PrP106-126 NH(2) on primary neuronal cultures were similar to those of the wild-type sequence. Conversely, astroglial proliferation is related to the presence of amyloid fibrils, suggesting that astrogliosis in prion encephalopathies without amyloid deposits is a mediated effect rather than a direct effect of disease-specific PrP isoforms.

Amides↗

PubMed1983

Rapid resolution of transferrin C subtypes through isoelectric focusing with 2-mercaptoethanol.

The technique of choice currently used for the detection of serum transferrin molecular polymorphism is isoelectric focusing on polyacrylamide slab gels. However, this procedure is unsatisfactory for routine purposes, since a long pretreatment of the serum with iron-donor compounds or neuraminidase is necessary in order to obtain a complete resolution of the transferrin molecule. A very fast and highly economical standardized procedure for transferrin typing which enables a fair molecular resolution within only 3 1/2 h is reported. Protracted pretreatment of serum with neuraminidase or with iron-donor compounds can be totally avoided. An ultrathin layer of polyacrylamide gel is employed for the run, using pH ranges of 4-6.5 or 5-7. A short pretreatment of serum with a 13% solution of 2-mercaptoethanol is performed before the samples are placed on the gel. This technique has been used to perform transferrin typing in 396 cord serum samples from newborn infants of Arezzo (Tuscany), without occurrence of artifacts or the appearance of extra bands in transferrin patterns.

Humans↗

PubMed2000

Hot-spot variations of Kaposi's sarcoma-associated herpesvirus latent nuclear antigen and application in genotyping by PCR-RFLP.

Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus-8) is aetiologically associated with Kaposi's sarcoma and several other lymphoproliferative disorders. The latent nuclear antigen (LNA) encoded by KSHV ORF73 has important functions in virus latent infection and shows molecular polymorphism. Sequence variations were identified in the internal repeat domain (IRD) of ORF73. DNA sequencing of ORF73 from one KSHV-infected cell line, PK-1, revealed that there were 558 bp (30.2%) deletions and 66 (3.6%) point mutations located mainly in repeat region 2, the glutamine-rich region of ORF73 IRD, compared with ORF73 of BC-1 KSHV. Similar sequence variations of ORF73 were also identified in two other isolates. None of the sequence variations caused any translational frame-shift in these four KSHV isolates examined, suggesting that LNA has a conservative function in virus latent infection. The frequent sequence variations in repeat region 2 of ORF73 IRD were also identified by PCR-RFLP genotyping in 26 KSHV isolates, suggesting that this region is a 'hot-spot' for genetic variations. Each Kaposi's sarcoma lesion sample contained one virus genotype with a unique RFLP pattern, indicating that in vivo KSHV infection was established with single predominate genotypes, which was further supported by the presence of invariable genotypes in multifocal lesions from individual KS patients. Four KSHV subtypes were classified based on the RFLP patterns that represent the patterns of DNA sequence variations in the ORF73 IRD. PCR-RFLP genotyping is capable of identifying LNA genetic variations and differentiating individual KSHV isolates, and thus may be useful for KSHV molecular epidemiology studies.

Antigens, Viral↗

PubMed2007

Quantitative and molecular analysis of buspirone hydrochloride polymorphs.

Quantitative and molecular analysis have been performed on two main polymorphs of buspirone hydrochloride (BUS-HCl). Quantitative analysis of solid-state composition of pharmaceutical powders is necessary to ensure safety and efficacy of drug substance and to validate the production processes. In this study, X-ray powder diffraction and differential scanning calorimetry have been used for the quantitative analysis of two polymorphic forms of BUS-HCl. In addition, single crystal X-ray study of Form 1 revealed its crystal structure, however, a similar study on Form 2 was not possible due to the difficulties encountered in producing it. Molecular analysis including partial charge analysis has been performed by using Gaussian simulation package to find the electro-negativity pattern in molecule. 1H and 13C solid-state NMR spectra of polymorphs were recorded and also regression equations and QM theory were developed to predict the 1H and 13C NMR spectra through the use of atomic environmental descriptors. The NMR differences between the two polymorphs were discussed by using prediction and experimental results and description of each NMR shift for carbon and hydrogen atoms.

Buspirone↗

PubMedDate not supplied

[Molecular diagnosis of hereditary diseases].

Molecular biology has produced important achievements in research, and provides useful applications to the clinical field. This is true today in diagnostics, and will be true in therapeutics tomorrow. The identification of pathogenic mutations through direct analysis of known genes allows diagnoses to be reached in a growing number of disorders. When mutations cannot be identified, familial linkage studies using polymorphic molecular markers will reach a diagnosis indirectly, most of the times. This is useful either presymptomatically or prenatally. The identification of genetic risk factors in targeted populations is becoming a means of prevention of multifactorial diseases. This approach opens a very large field of applications of molecular genetics in clinical practice. Basic concepts of molecular genetics are briefly reviewed, and the principles of diagnostics in hereditary diseases are approached via a few representative examples.

Adenomatous Polyposis Coli↗

PubMed1992

Theoretical study of near neutrality. II. Effect of subdivided population structure with local extinction and recolonization.

There are several unsolved problems concerning the model of nearly neutral mutations. One is the interaction of subdivided population structure and weak selection that spatially fluctuates. The model of nearly neutral mutations whose selection coefficient spatially fluctuates has been studied by adopting the island model with periodic extinction-recolonization. Both the number of colonies and the migration rate play significant roles in determining mutants' behavior, and selection is ineffective when the extinction-recolonization is frequent with low migration rate. In summary, the number of mutant substitutions decreases and the polymorphism increases by increasing the total population size, and/or decreasing the extinction-recolonization rate. However, by increasing the total size of the population, the mutant substitution rate does not become as low when compared with that in panmictic populations, because of the extinction-recolonization, especially when the migration rate is limited. It is also found that the model satisfactorily explains the contrasting patterns of molecular polymorphisms observed in sibling species of Drosophila, including heterozygosity, proportion of polymorphism and fixation index.

Animals↗

PubMed1998

Polymorphic DNA markers in the genome of parasitic nematodes.

Polymorphic molecular markers are being identified to characterize the genomes of parasitic nematodes. The aim is to construct a map with markers evenly spread over the six chromosomes. With such a map, regions can be identified that are under selection pressure when attempts are being made to eradicate worms, be it by drugs, vaccines or genetic resistance in the sheep. Several types of markers have been developed, microsatellites, transposon-associated markers, amplified fragment length polymorphism (AFLP) and expressed sequence tag (EST) markers. Linkage groups can be constructed using several genetic crosses between inbred and drug resistant strains. EST markers will be especially important for comparative mapping with the genome of Caenorhabditis elegans, and therefore localization of the linkage group on a chromosome. It will then be possible to identify functional genes close to markers that have changed allele frequencies under selection pressure and identify the mechanisms of resistance to parasite control.

Animals↗

PubMed1984

Group selection for a polygenic behavioral trait: estimating the degree of population subdivision.

For assessing the degree of population subdivision, and therefore the extent to which group selection might favor an altruistic trait, an appropriate measure is Nei's GST, defined by (F0-F)/(1-F). F0 is the probability that two alleles drawn from the same group are identical in state and F is the probability for two alleles drawn at random from the entire population. These probabilities can be assessed from molecular polymorphisms. GST has a number of properties that make it useful for empirical studies. When the mutation rate is small relative to the migration rate and the reciprocal of the group size, GST depends mainly on the absolute number of migrants per generation, moves rapidly to near equilibrium, and is independent of the number of alleles. The relative homogenizing effect of migration in the island and stepping-stone models is not as different as might be expected; one immigrant chosen randomly from the rest of the population is only one to two times as effective as one from a neighboring group, appreciably exceeding 2 only when there are 1000 or more groups. The use of molecular data to estimate the degree of population subdivision may permit testable predictions of the extent of altruistic behavior.

Alleles↗

PubMed2005

Linear allele-specific long-range amplification: a novel method of long-range molecular haplotyping.

Haplotypes have been repeatedly shown to be more powerful than collections of single-locus markers in gene-mapping studies. Various haplotyping methods including statistical estimation are employed but molecular haplotyping, the acquisition of information directly on physical DNA sequences, has been in demand for its accuracy and independence from family pedigrees. We investigated the allelic specificity of long-range PCR, which was successful for long-range haplotyping in recent reports, and found problems of initial mispriming and crossover amplification significantly confounded its application. Based on these observations, we designed a novel method based on linear amplification of a hemizygous DNA segment with a single phosphorothioate-modified oligonucleotide. Our results revealed, with a single nucleotide polymorphism as the discriminative marker, downstream haplotypes of 14-15 kb DNA segment could be confidently scored. With two rounds of the method and five single nucleotide polymorphisms, molecular haplotypes of 29.3 kb spanning the HCR and CDSN genes, two genes associated with the susceptibility of psoriasis, of 11 members, belonging to a CEPH family, were revealed. Clear Mendelian segregation of 35 highly heterozygous SNPs confirmed the accuracy of the method. Problems of low specificity associated with long-range PCR were not observed. The simplicity, along with long-sequence accessibility and feasibility of a single nucleotide difference as the discriminative marker indicated our method holds promise for future gene-mapping studies.

Adenomatous Polyposis Coli↗

PubMed2001

Acetylcholinesterase in Alzheimer's disease.

Since the discovery of the cholinergic deficit in Alzheimer disease (AD), acetylcholinesterase (AChE) has been widely investigated in tissues involved in the disease. These studies showed modifications in AChE activity and changes in its polymorphism in brain as well as in cerebro-spinal fluid (CSF) and blood. The co-localization of the enzyme in the senile plaque provided evidence of its anomalous features. It has been also shown that AChE forms a stable complex with senile plaque components through its peripheral anionic site. Moreover, the neurotoxicity of amyloid components is increased by the presence of AChE. The occurrence of an altered glycosylation of some AChE forms in AD is closely related to the presence of amyloid formations. Literature on expression, relationships and modifications in the molecular polymorphism of AChE, in brain, CSF and blood in AD is reviewed.

Acetylcholine↗

PubMed2004

The Allonemobius-Wolbachia host-endosymbiont system: evidence for rapid speciation and against reproductive isolation driven by cytoplasmic incompatibility.

Evidence for the evolution of fertilization incompatibilities and rapid speciation can be biased by the occurrence of hybridization and reproductive endosymbionts such as Wolbachia. For example, patterns of mitochondrial DNA (mtDNA) variation can be obscured by mitotypes hitchhiking on extrachromosomal elements like Wolbachia, while such endosymbionts can also induce phenotypes that mirror the operation of intrinsic fertilization incompatibilities between species. Therefore, before strong inferences can be drawn concerning the rates and processes of speciation in arthropod systems, we must first assess whether extrinsic endosymbionts obscure patterns of speciation. Here, I use the Allonemobius fasciatus-socius species complex to determine what role Wolbachia has played in the presumed rapid divergence of this complex by analyzing patterns of mtDNA and nuclear DNA variation in conjunction with sequence and cytoplasmic incompatibility data on Wolbachia. Data on molecular variation suggest that Wolbachia has not induced a strong selective sweep of the mitochondrial genome; nor does Wolbachia appear to induce cytoplasmic incompatibility. Preliminary evidence indicates that a third species identified within this complex, A. sp. nov. Tex, is partially reproductively isolated from A. socius, its closest relative, via conspecific sperm precedence or some form of postzygotic isolation. Moreover, shared mitotypes between A. sp. nov. Tex and A. socius may indicate the occurrence of a hybrid zone between these species near the border of Texas and Louisiana, although they may also represent shared ancestral polymorphisms. Molecular data also indicate that all three species in this complex diverged from a common ancestor as recently as 3000-30,000 years ago. Finally, the radiation of this complex from its ancestral population likely occurred in the presence of one strain of Wolbachia, thus suggesting a minimal role for Wolbachia during this burst of speciation. In total, barriers to gene flow do appear to have evolved very rapidly in this group of crickets.

Animals↗

PubMed2001

Two new variants of the lipocalin allergen Bos d 2.

Allergens from various sources have been shown to comprise several isoforms. In the present study, a series of chromatographic steps was carried out to separate the lipocalin allergen Bos d 2 isoforms present in cow dander. Subsequent HPLC-MS-MS analyses revealed two new Bos d 2 variants. In one of the proteins, tyrosine (Y83) was substituted by aspartic acid, and in the other protein valine (V102) was replaced by alanine. We propose the three Bos d 2 variants be named as Bos d 2.0101 (previously sequenced Bos d 2), Bos d 2.0102 and Bos d 2.0103. Our results suggest that molecular polymorphism is a common property among lipocalin allergens. Since allergen isoforms may show variation in their IgE binding and/or T-cell reactivity, all of the many allergen forms should be taken into account when planning preparations for immunotherapy.

Allergens↗

PubMed1980

Light microscopic localization of acid phosphatase in different tissue cells of the albino rat.

The enzyme acid phosphatase (orthophosphoric monoester phosphohydrolase, EC 3.1 3.2), often referred to as "non-specific acid phosphomonoesterase" because of histochemical and biochemical polymorphisms and ubiquity, is one of the most thoroughly studied enzyme in mammalian tissues. The aim of the present work was to outline the functional characteristics of this enzyme by extrapolating the results of light microscopic investigations. A diffuse intracytoplasmic acid phosphatase activity was detected in the epinephrine-producing cells of the adrenal medulla. Various forms of lysosomes were observed to exert acid phosphatase activity in bronchial and bronchiolar epithelia, hepatocytes, Kupffer cells and in the walls of brain vessels. Pseudounipolar ganglion cells and certain neurons of the medulla oblongata were found to contain acid phosphatase in intracellular membrane systems. Biochemically, acid phosphatase consists of more than four isozymes each of them possessing antigenically diverse molecular forms suggesting molecular polymorphism. Histochemical and biochemical polymorphisms of acid phosphatase are considered to be due to the accommodation to the pleomorphic appearance of a sole chemical bond.

Adrenal Medulla↗

PubMed2005

Molecular genetic testing of polymorphisms associated with venous thrombosis: a review of molecular technologies.

The growing knowledge of genetic polymorphisms predisposing to venous thrombosis has increased the demand for genetic testing of associated risk factors. This has prompted the need for simple, fast, reliable, and cost-effective genotyping methods for identification of those mutations. In the past decade, a large variety of DNA mutation analysis methods have been developed for detection of genetic variants associated with venous thrombosis, including PCR-based and PCR-independent technologies. Each of these technologies possesses unique advantages, but all have a common goal of simplifying and expediting mutation analysis. This review describes some of the commonly used technologies and commercially available platforms employed in clinical laboratories for genetic testing of thrombophilia. The choice of a technology for each individual laboratory would primarily depend on the specific requirements for the assay's accuracy, reliability, speed, throughput, and cost-effectiveness.

DNA Mutational Analysis↗

PubMed2005

The role of molecular structure in the crystal polymorphism of local anesthetic drugs: crystal polymorphism of local anesthetic drugs, part X.

PURPOSE: This report is the résumé of a comprehensive investigation on the solid-state properties and the crystal polymorphism of the structurally homogenous class of local anesthetic drugs. The goal is to explore the relationship between crystal polymorphism and molecular structural features. METHODS: A salt form (mostly the hydrochloride) as well as the free base of 24 local anesthetics has been characterized by means of thermomicroscopy, differential scanning calorimetry, pycnometry, Fourier transform infrared, Fourier transform Raman, and solid-state NMR spectroscopies, as well as X-ray diffraction methods (single crystal, powder). RESULTS: Based on the thermochemical data, the relative thermodynamic stabilities of the different crystal forms of each polymorphic system were evaluated and visualized as semiquantitative energy/temperature diagrams. CONCLUSION: This study is the first step in recognizing relationships between the structure and the solid-state properties within this limited group of active substances with common structural elements. The results clearly show that there are certain relationships, but, to understand the phenomenological behavior in more detail on a molecular level, more structural information must be collected and analyzed by computational methods.

Adsorption↗

PubMed1998

Recent advances in understanding the molecular basis of polymorphisms in genes encoding cytochrome P450 enzymes.

The cytochrome P450 superfamily is known to exhibit a high degree of genetic polymorphism and polymorphisms associated with absent or low enzyme activity in CYP2D6, CYP2C19 and CYP2C9 are particularly well studied. However, despite early reports of strong disease associations for particular CYP2D6 phenotypes, these have not been confirmed in recent, more detailed studies and it now appears that analysis of CYP2D6, CYP2C19 and CYP2C9 genotype is of most value in predicting metabolism of specific drugs. Polymorphisms in other cytochrome P450 genes are less well studied and appear not to be associated with complete absence of enzyme activity. We have recently carried out studies of polymorphism in both CYP1A1 and CYP2E1. The molecular basis of the apparent CYP1A1 'high inducibility' polymorphism was investigated by studying CYP1A1 and Ah receptor polymorphisms in a group of phenotyped individuals who were genotyped both for known and novel CYP1A1 and Ah receptor polymorphisms. Three novel polymorphisms in CYP1A1 (C(-459)T, G(-469)A and C(4151)T) and one in the Ah receptor (G(1768)A; V(570)I) were detected by single strand conformational polymorphism analysis and DNA sequencing. Among both novel and previously known polymorphisms, only the Ah receptor G(1721)A polymorphism, which has an allele frequency of 0.12 in Caucasians and was detected previously in a Japanese population, was significantly associated with high induced CYP1A1 activity. In the case of CYP2E1, we have detected three polymorphisms in the promoter region (A(-316)G, T(-297)A and G(-35)T) and one in the coding sequence (G(4804)A; V(179)I) by screening Caucasian DNA samples. The significance of these alleles has been investigated but only G(-35)T combined with T(-297)A, which has an allele frequency of 0.05, appears to be of functional significance, with an apparent 1.8-fold increase in levels of transcriptional activity compared with the wild-type.

Animals↗

PubMed2002

Molecular variation of HLA class I genes in the Corsican population: approach to its origin.

Three human leucocyte antigen (HLA) class I loci (HLA-A, -B and -Cw) were typed for the first time at the DNA level in the Corsican population. This analysis was performed on 100 individuals of Corsican origin living in central Corsica (46 individuals) and in south-western Corsica (54 individuals). The genetic structure of these two subpopulations was analysed on the basis of the molecular polymorphisms of the HLA-A, -B and -Cw genes. A phylogenetic and a haplotypic analysis were performed. The genotypic analysis did not detect genetic differentiation. Examination of the allelic and haplotypic frequencies did, however, reveal some significant differences between the two zones. Similarities with the Sardinian population were found, and were particularly evident in the south-western sample. However, Corsica has probably been subject to greater West European influence, which can be seen in the Corte sample (Haute Corse).

Evolution, Molecular↗