PubMed Health⌕ Search

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 487 records · Page 27Linked to original sources
PubMed2002

Molecular bases for human complement C7 polymorphisms, C7*3 and C7*4.

Complement C7 is one of the components of membrane attack complex (MAC) generated by the terminal complement cascade. C7 protein is polymorphic and most of its polymorphisms have been identified using isoelectric focusing (IEF), which detects protein charge differences. To date, the molecular bases of the polymorphisms detected by IEF have not been determined. In this paper, we describe the structural bases of two C7 IEF-detected polymorphisms, C7*3 and C7*4, both of which are common in Asian populations. C7*3 resulted from substitution of cysteine (Cys) at amino acid residue 106 by charged arginine (Arg; C106R), while charged lysine (Lys) at amino acid residue 398 was replaced by neutral glutamine (Gln; K398Q) in C7*4. As C7*3 is hypomorphic, it is important to study its possible associations with diseases such as immunological disorders and infections. We present genetic bases for this C7 polymorphism, which we determined using polymerase chain reaction (PCR)-based genotyping, a simple and accurate method suitable for large-scale studies.

Base Sequence↗
PubMed2004

[Advances on inhibin genes].

Inhibins are gonadal glycoprotein hormones belonging to the transforming growth factor-beta superfamily that act to suppress pituitary follicle-stimulating hormone synthesis and secretion. In this paper, we briefly introduced the cloning, structure, localization, polymorphism, expression, molecular regulation of inhibin-alpha(INHA), -betaA (INHBA) and -beta B (INHBB) subunit genes and their relationships with reproductive performance and cancer. The inhibin genes (INHA, INHBA and INHBB) had significant effect on litter size in sheep. The ovine INHA, INHBA and INHBB genes had been mapped to chromosomes 2q41-->q43, 4q26 and 2q31-->q33, respectively. The female mice carrying INHBB mutations suffered from distinct developmental and reproductive defects. The INHA gene was significantly associated with premature ovarian failure in women.

Animals↗
PubMed1996

Molecular genetic examination of the polymorphic Arctic charr Salvelinus alpinus of Thingvallavatn, Iceland.

Thingvallavatn, Iceland contains two sympatric morphotypes (benthic and limnetic) of Arctic charr Salvelinus alpinus. Each morphotype is composed of two morphs and these differ markedly in ecology, behaviour and life history. We used molecular genetic approaches to test whether (i) genetic heterogeneity exists among morphs and (ii) if morphs arose in allopatry and came into secondary contact or arose sympatrically within the lake through genetic segregation and/or phenotypic plasticity. Direct sequencing of 275 bp of the mitochondrial DNA (mtDNA) control region, mtDNA restriction fragment length polymorphisms and single locus minisatellite analyses detected insufficient variation to test our hypotheses. Analysis of multilocus minisatellite band sharing detected no significant differences between morphs within the same morphotype. However, significant differences among morphs belonging to different morphotypes suggest some genetic heterogeneity in Thingvallavatn charr. Limnetic charr from Thingvallavatn were more similar to sympatric benthic charr than to allopatric limnetics from two other Icelandic lakes. This suggests that the Thingvallavatn morphs arose sympatrically within the lake rather than in allopatry followed by secondary contact.

Animals↗
PubMed1999

Molecular characterization of MRJP3, highly polymorphic protein of honeybee (Apis mellifera) royal jelly.

Major proteins of honey bee (Apis mellifera) royal jelly are members of the MRJP protein family. One MRJP protein termed MRJP3 exhibits a size polymorphism as detected by SDS-PAGE. In this report we show that polymorphism of the MRJP3 protein is a consequence of the polymorphism of a region with a variable number of tandem repeats (VNTR) located at the C-terminal part of the MRJP3 coding region. We present the characterization of five polymorphic alleles of MRJP3 by DNA sequencing. By PCR analyses, at least 10 alleles of distinct sizes were found in randomly sampled bees. Studies with nurse bees from a single honeybee colony revealed both Mendelian inheritance and very high variability of the MRJP3 genomic locus. The high variability and simple detection of the MRJP3 polymorphism may be useful for genotyping of individuals in studies of the honeybee.

Alleles↗
PubMed1991

The human transmembrane secretory component (poly-Ig receptor): molecular cloning, restriction fragment length polymorphism and chromosomal sublocalization.

The human transmembrane secretory component (SC) mediates glandular translocation of polymeric IgA and IgM into exocrine secretions. A 2898-bp cDNA clone, encoding the entire sequence of the human transmembrane SC, was isolated from a colonic adenocarcinoma cell line cDNA library. The deduced amino-acid sequence had a length of 764 residues and showed an overall similarity of 56% and 64% with the rabbit and rat counterpart, respectively. A restriction fragment length polymorphism (RFLP) was found with PvuII, revealing a two-alle RFLP with an autosomal codominant inheritance pattern and allele frequencies of 0.65 and 0.35. Southern blot analysis of human-rodent somatic hybrid panels, including hybrids with translocation chromosomes carrying different parts of chromosome 1, assigned the SC gene to 1q31-q42, thus confirming a previously reported provisional assignment.

Amino Acid Sequence↗
PubMed2004

Molecular basis of the size polymorphism of the first intron of the Adh-1 gene of the mediterranean fruit fly, Ceratitis capitata.

The first intron of the gene encoding one of the alcohol dehydrogenase isoenzymes (ADH-1) in Ceratitis capitata is highly polymorphic in size. Five size variants of this intron were isolated from different strains and populations and characterized. Restriction map and sequence analysis showed that the intron size polymorphism is due to the presence or absence of (a) a copy of a defective mariner-like element, postdoc; (b) an approximately 550-bp 3' indel which exhibits no similarity to any known sequence; and (c) a central duplication of 704 bp consisting of part of the 3' end of the postdoc element, the region between postdoc and the 3' indel, and the first 20 bp of the 3' indel. The homologous Adh-1 intron was amplified from the congeneric species, Ceratitis rosa, in order to obtain an outgroup for comparative and phylogenetic analyses. The C. rosa introns were polymorphic in size, ranging from about 1100 to 2000 bp, the major difference between them being the presence or absence of a mariner-like element Crmar2, unrelated to the postdoc element. Phylogenetic analysis suggests that the shorter intron variants in C. capitata may represent the ancestral form of the intron, the longest variants apparently being the most recent.

Alcohol Dehydrogenase↗
PubMed1976

Population genetics and molecular evoulution.

Recent studies of evolution and polymorphism at the molecular level (i.e, at the level of internal structure of the gene) have brought many puzzling as well as enlightening results. It appears that, in addition to natural selection, chance (in the form of random gene frequency drift) is playing a much larger part than previously considered. Futhermore, natural selection is likely to be based more directly on the secondary and the higher order structure of informational macromolecules rather than ecological conditions, usually in the form of negative selection. In this respect, there is growing evidence suggesting that very slightly deleterious mutations whose selective disadvantages are not excessively large as compared with the mutation rates are playing a significant role in variation and evoulution at the molecular level.

Alleles↗
PubMed1995

Major molecular weight heterogeneity of estrogen receptor from breast cancer is not related to neoplasia.

Recent investigation from our laboratory revealed that the estrogen receptor (ER) from breast cancer is characterized by a high molecular weight polymorphism: SDS-polyacrylamide gel electrophoresis of [3H]-tamoxifen aziridine ([3H]-TAZ) labeled cytosols usually display several bands corresponding to the native receptor (67 KDa) and lower molecular cleavage products. High frequency of such altered receptors was confirmed here by size exclusion FPLC of [125I]-E2 labeled cytosols from a series of 98 breast cancers: on the average, 60% of the ER molecules were strongly degraded (Mr < or = 37 KDa). The absence of transcriptional activating domains (ABC domains) in such receptors was further demonstrated by assessing their ability to bind to hydroxylapatite (HAP). Thus, in presence of 500 mM KCI, 55% of ERs from another series of 54 cytosols failed to strongly adsorb to this phosphocalcic matrix, a characteristic property of receptors without exposed ABC domains. Finally, [3H]-TAZ labeled cytosols from normal uterine tissue and MCF-7 human breast cancer cells growing in nude mice displayed identical multibands electrophoretic patterns revealing in both cases native and cleaved receptors. Since latter receptor forms were never detected in MCF-7 cells growing in monolayer culture, we put forward the hypothesis that they were produced under the action of proteolytic enzymes acting at the time of tissue processing. Hence, most of the truncated receptors detected in human breast cancer cytosols should not be markers of malignancy.

Animals↗
PubMed1996

Fingerprinting of HLA class I genes for improved selection of unrelated bone marrow donors.

The degree of matching of HLA genes between the selected donor and recipient is an important aspect of the selection of unrelated donors for allogeneic bone marrow transplantation (UBMT). The most sensitive methods currently used are serological typing of HLA class I genes, mixed lymphocyte culture (MLC), IEF and molecular genotyping of HLA class II genes by direct sequencing of PCR products. Serological typing of class I antigenes (A, B and C) fails to detect minor differences demonstrated by direct sequencing of DNA polymorphic regions. Molecular genotyping of HLA class I genes by DNA analysis is costly and work-intensive. To improve compatibility between donor and recipient, we have set up a new rapid and non-radioisotopic application of the 'fingerprinting PCR' technique for the analysis of the polymorphic second exon of the HLA class I A, B and C genes. This technique is based on the formation of specific patterns (PCR fingerprints) of homoduplexes and heteroduplexes between heterologous amplified DNA sequences. After an electrophoretic run on non-denaturing polyacrylamide gel, different HLA class I types give allele-specific banding patterns. HLA class I matching is performed, after the gel has been soaked in ethidium bromide or silver-stained, by visual comparison of patients' fingerprints with those of donors. Identity can be confirmed by mixing donor and recipient DNAs in an amplification cross-match. To assess the technique, 10 normal samples, 22 related allogeneic bone marrow transplanted pairs and 10 unrelated HLA-A and HLA-B serologically matched patient-donor pairs were analysed for HLA class I polymorphic regions. In all the related pairs and in 1/10 unrelated pairs, matched donor-recipient patterns were identified. This new application of PCR fingerprinting may confirm the HLA class I serological selection of unrelated marrow donors.

Base Sequence↗
PubMed1986

Molecular analysis of a deletion polymorphism in alpha satellite of human chromosome 17: evidence for homologous unequal crossing-over and subsequent fixation.

The human alpha satellite DNA family is organized into chromosome-specific subsets characterized by distinct higher-order repeats based on a approximately 171 basepair monomer unit. On human chromosome 17, the predominant form of alpha satellite is a 16-monomer (16-mer) higher-order repeat present in 500-1000 copies per chromosome 17. In addition, less abundant 15-monomer and 14-monomer repeats are also found constitutively on chromosome 17. Polymorphisms in the form of different higher-order repeat lengths have been described for this subset, the most prominent polymorphism being a 13-monomer (13-mer) higher-order repeat present on approximately 35% of all chromosomes 17. To investigate the nature of this polymorphism, we have cloned, sequenced and compared the relevant regions of the 13-mer to the previously characterized 16-mer repeat. The results show that the repeats are virtually identical, with the principal difference being the exclusion of three monomers from the 13-mer repeat. We propose that the 13-mer is the product of an isolated homologous recombination event between two monomers of the 16-mer repeat. Sequence comparisons reveal the approximate site of recombination and flanking regions of homology. This recombination site corresponds to a position within the alphoid monomer which has been previously implicated in an independent homologous recombination event, suggesting that there may exist a preferred register for recombination in alphoid DNA. We suggest that these events are representative of an ongoing process capable of reorganizing the satellite subset of a given chromosome, thereby contributing to the establishment of chromosome-specific alpha satellite subsets.

Base Sequence↗
PubMed1985

A new restriction fragment length polymorphism in the haptoglobin gene region.

Direct gene analysis of the haptoglobin gene region was carried out by Southern blotting using an Hp cDNA as probe. Two types of polymorphism were observed: one due to intragenic duplication, is characterized by a constant fragment length difference of 1700bp observed with several enzymes and by complete correspondence with the protein molecular weight polymorphism; the second type, due to point mutation, was represented by two additional restriction sites for Eco RI and Pst I, with a frequency comparable to that of other genes. These two mutations segregated together in families, suggesting that the recently described Hp related gene is closely linked to the Hp gene. Moreover, they were completely associated with each other. The evolutionary significance of this finding is discussed.

Alleles↗
PubMed2002

Polymorphism in major urinary proteins: molecular heterogeneity in a wild mouse population.

Major urinary proteins (MUPs) are present in high levels in the urine of mice, and the specific profile of MUPs varies considerably among wild-caught individuals. We have conducted a detailed study of the polymorphic variation within a geographically constrained island population, analyzing the MUP heterogeneity by isoelectric focusing and analytical ion exchange chromatography. Several MUPs were purified in sufficient quantities for analysis by electrospray ionization mass spectrometry and MALDI-TOF mass spectrometry of endopeptidase Lys-C peptide maps. The results of such analyses permitted the identification of three new MUP allelic variants. In each of these proteins, the sites of variation were located to a restricted segment of the polypeptide chain, projecting to a patch on the surface of the protein, and connected to the central lipocalin calyx through the polypeptide backbone. The restriction of the polymorphic variation to one segment of the polypeptide may be of functional significance, either in the modulation of ligand release or in communication of individuality signals within urinary scent marks.

Animal Communication↗
PubMed2001

Molecular modelling of disease-causing single-nucleotide polymorphisms in collagen.

The purpose of the work was to investigate at the molecular structural and energy levels the consequence of amino acid substitutions in collagen that cause systemic diseases. The data have been systematized on defects in human collagen III, and the patterns of single-nucleotide polymorphisms collected. Then molecular mechanics calculations were performed for native and mutant collagen molecule fragments. The observed energy components and structural alterations that accompany particular amino acid substitutions were used to propose an interpretation of negative consequences in terms of stability and hydration of the macromolecule.

Amino Acid Substitution↗
PubMed2006

Discriminant analysis of DNA polymorphisms in herpes simplex virus type 1 strains involved in primary compared to recurrent infections.

The restriction fragment length polymorphism (RFLP) was analyzed using a set of herpes simplex virus type 1 (HSV-1) strains isolated from oro-facial lesions (oro-facial site collection), which was composed of two subsets: one subset consisted of 57 strains from primary oro-facial lesions, and the other of 47 strains from recurrent oro-facial lesions of patients complicated by factors possibly triggering the recurrence (e.g. malignancy, operation, and treatment of dental caries). RFLP analysis was carried out previously on two other sets of HSV-1 strains: one set was from genital lesions (genital site collection), and the other was from non-genital lesions (non-genital site collection). Discriminant analysis was carried out on the three sets of HSV-1 strains: the criterion variable had two values of primary infection or recurrence, and the predictor variables were 20 RFLPs. The degrees of separation between primary infection and recurrence increased in the order oro-facial site collection, genital site collection, and non-genital site collection. The results of discriminant analysis in this study confirmed that reactivation of HSV-1 infection is influenced by triggering factors and the site of infection, thereby suggesting the capabilities of multivariate analysis (including discriminant analysis) with DNA polymorphisms for molecular epidemiological studies.

Animals↗
PubMed2006

Searching for polymorphisms that affect gene expression and mRNA processing: example ABCB1 (MDR1).

Cis-acting genetic variations can affect the amount and structure of mRNA/protein. Genomic surveys indicate that polymorphisms affecting transcription and mRNA processing, including splicing and turnover, may account for the main share of genetic factors in human phenotypic variability; however, most of these polymorphisms remain yet to be discovered. We use allelic expression imbalance (AEI) as a quantitative phenotype in the search for functional cis-acting polymorphisms in many genes, including ABCB1 (multidrug resistance 1 gene, MDR1, Pgp). Previous studies have shown that ABCB1 activity correlates with a synonymous polymorphism, C3435T; however, the functional polymorphism and molecular mechanism underlying this clinical association remained unknown. Analysis of allele-specific expression in liver autopsy samples and in vitro expression experiments showed that C3435T represents a main functional polymorphism, accounting for 1.5- to 2-fold changes in mRNA levels. The mechanism appears to involve increased mRNA turnover, probably as a result of different folding structures calculated for mRNA with the Mfold program. Other examples of the successful application of AEI analysis for studying functional polymorphism include 5-HTT (serotonin transporter, SLC6A4) and OPRM1 (mu opioid receptor). AEI is therefore a powerful approach for detecting cis-acting polymorphisms affecting gene expression and mRNA processing.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

An ab initio calculation of 17O and 29Si NMR parameters for SiO2 polymorphs.

Ab initio molecular orbital calculations (Hartree-Fock, HF and density functional theories, DFTs) have been carried out for SiO2 polymorphs coesite, low cristobalite, and alpha-quartz, in order to investigate the reliability of this method for predicting 29Si and 17O nuclear magnetic resonance (NMR) properties of silicates. Oxygen- and silicon-centered clusters consisting of one (1T) to three tetrahedral (3T) shells (one to four atomic shells), taken from real crystal structure, have been investigated. It is found that for reasonable predication of both the 29Si and 17O chemical shifts (deltaSi and delta(i)O), the minimum cluster is one that gives the correct second neighbors to the nucleus of interest. Both the delta(i)Si and delta(i)O have reached convergence with respect to cluster size at the OH-terminated two tetrahedral (2T) shell (three atomic shells around Si and four atomic shells around O) model. At convergence, the calculated delta(i)Si values agree well (within +/- 1 ppm) with experimental data. The calculated 17O electric field gradient (EFG)-related parameters also agree with experimental data within experimental uncertainties. The calculation also reproduces small differences in delta(i)O for O sites with similar tetrahedral connectivities, but shows deviations up to about 10 ppm in relative difference for O sites with different tetrahedral connectivities. The poor performance for the latter is mainly due to the approximations of the HF method. Our study thus suggests that the ab initio calculation method is a reliable mean for predicting 29Si and 17O NMR parameters for silicates. Such an approach should find application not only to well-ordered crystalline phases, but also to disordered materials, by combining with other techniques, such as the molecular dynamics simulation method.

Crystallization↗
PubMed2002

Land barriers and open oceans: effects on gene diversity and population structure in Avicennia germinans L. (Avicenniaceae).

Avicennia germinans L. is a widespread mangrove species occupying the west coast of Africa and the Atlantic and Pacific coasts of the Americas from the Bahamas to Brazil and Baja California to Peru. An amplified fragment length polymorphism (AFLP) molecular analysis was carried out to assess genetic architecture within this species and to evaluate the effects of the Atlantic Ocean and the Central American Isthmus (CAI) on population and regional genetic diversity and differentiation. In total, 349 polymorphic AFLP fragments were identified among 144 individuals from 14 populations from the east Atlantic, west Atlantic and east Pacific. Levels of genetic diversity varied considerably among populations, but were generally higher in populations from the east Atlantic. Regional differentiation between the Pacific coast and Atlantic populations was greater than between east and west Atlantic populations, suggesting that the CAI has had an important influence on population genetic structure in this species. The lower level of divergence of east Atlantic from west Atlantic populations suggests some dispersal across the Atlantic Ocean, although migration rates are probably low; Nm from GST equal to 0.41 and accumulation of private and rare alleles in the east Atlantic. Population differentiation did not appear to follow an isolation by distance model and has probably resulted from complex patterns of population bottlenecks, and founder events due to landscape changes during the Pleistocene, particularly in the west Atlantic. The molecular data provide no support for the treatment of east Atlantic populations as a separate species A. africana.

Genes, Plant↗