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 523 records · Page 29Linked to original sources
PubMed1997

The influence of the angiotensin I converting enzyme genotype in familial hypertrophic cardiomyopathy varies with the disease gene mutation.

Familial hypertrophic cardiomyopathy is an autosomal dominant genetically heterogeneous disease characterized by a partial penetrance and variable expressivity. Previous studies showed that the extent of hypertrophy is influenced by the angiotensin I converting enzyme insertion/deletion (I/D) polymorphism. Recently, molecular genetic analysis revealed the existence of healthy carriers and that as many as a quarter of genetically affected individuals do not express the disease. This data prompted us to re-investigate the role of the angiotensin I converting enzyme polymorphism on hypertrophy by assessing both clinically affected individuals and healthy carriers. For this, several families with mutations in the cardiac myosin binding protein C or the beta-myosin heavy chain genes were analysed. The mean maximal intraventricular septum thickness was compared as a function of angiotensin I converting enzyme genotypes in all genetically affected individuals (n = 114), and in subsets of subjects carrying either a splice acceptor site mutation in the cardiac myosin binding protein C gene (n = 33), or various missense mutations in the cardiac beta-myosin heavy chain gene (n = 81) or finally, mutation in the Arg403 codon of the beta-myosin heavy chain gene (n = 54). Significant association between the D allele and hypertrophy was observed only in the case of Arg403 codon mutations (mean septum thickness for subjects with the DD genotype: 19.3 +/- 2.7 mm: with the ID genotype: 13.4 +/- 1.3 mm and with the II genotype: 11.0 +/- 0.9 mm; P < 0.02). These results were confirmed by the chi 2 test showing an over-representation of DD genotype in patients carrying an Arg403 codon mutation associated with septal hypertrophy (P < 0.05). Our data confirms that the angiotensin I converting enzyme genotypes can influence the phenotypic expression of hypertrophy and shows that this influence depends on the mutation, raising the concept of multiple genetic modifiers in familial hypertrophic cardiomyopathy.

Adult↗
PubMed1999

RNA-controlled polymorphism in the in vivo assembly of 180-subunit and 120-subunit virions from a single capsid protein.

Repeated, specific interactions between capsid protein (CP) subunits direct virus capsid assembly and exemplify regulated protein-protein interactions. The results presented here reveal a striking in vivo switch in CP assembly. Using cryoelectron microscopy, three-dimensional image reconstruction, and molecular modeling, we show that brome mosaic virus (BMV) CP can assemble in vivo two remarkably distinct capsids that selectively package BMV-derived RNAs in the absence of BMV RNA replication: a 180-subunit capsid indistinguishable from virions produced in natural infections and a previously unobserved BMV capsid type with 120 subunits arranged as 60 CP dimers. Each such dimer contains two CPs in distinct, nonequivalent environments, in contrast to the quasi-equivalent CP environments throughout the 180-subunit capsid. This 120-subunit capsid utilizes most of the CP interactions of the 180-subunit capsid plus nonequivalent CP-CP interactions. Thus, the CP of BMV, and perhaps other viruses, can encode CP-CP interactions that are not apparent from mature virions and may function in assembly or disassembly. Shared structural features suggest that the 120- and 180-subunit capsids share assembly steps and that a common pentamer of CP dimers may be an important assembly intermediate. The ability of a single CP to switch between distinct capsids by means of alternate interactions also implies reduced evolutionary barriers between different capsid structures. The in vivo switch between alternate BMV capsids is controlled by the RNA packaged: a natural BMV genomic RNA was packaged in 180-subunit capsids, whereas an engineered mRNA containing only the BMV CP gene was packaged in 120-subunit capsids. RNA features can thus direct the assembly of a ribonucleoprotein complex between alternate structural pathways.

Bromovirus↗
PubMed2000

Identification of missense mutations in the SRD5A2 gene from patients with steroid 5alpha-reductase 2 deficiency.

BACKGROUND AND OBJECTIVE: Mutations of the steroid 5alpha-reductase type 2 (SRD5A2) gene in karyotypic males result in a spectrum of external genitalia phenotypes ranging from complete female to nearly complete male. Here we performed genomic DNA analyses from individuals bearing the enzyme deficiency in order to detect the molecular abnormalities. PATIENTS: Four unrelated 46,XY patients of Mexican origin with ambiguous external genitalia were studied. A fertile, phenotypically normal male was also included. MEASUREMENTS: Coding sequence abnormalities of the SRD5A2 gene were assessed by exon-specific polymerase chain reaction, single-stranded conformational polymorphism and sequencing analysis. RESULTS: Five different missense mutations (two of them novel mutations) were identified. Three subjects presented homozygous single base mutations. These were located at exon 2 (G115D), exon 4 (P212R) and exon 5 (R246Q), and such changes have been described previously. The fourth patient was a compound heterozygote who presented two mutations located in exons 1 and 2. We found a hitherto unreported G --> A transition at the second nucleotide of codon 85 in exon 1 (GGC --> GAC), substituting glycine for aspartic acid (G85D). This patient also presented an identical alteration at codon 115 of exon 2, which was carried by his father (G115D). Finally, in another subject who was included originally as a control, we found a C --> A transversion (yet undescribed) at codon 245 in exon 5 (S245Y). CONCLUSIONS: Four different single base mutations that cause amino acid substitutions were detected in the steroid 5alpha-reductase type 2 gene of affected individuals. One patient and a normal control had two previously undescribed mutations. Although in the latter individual we cannot exclude the possibility that the base change is a genetic polymorphism, the molecular screening of 100 chromosomes suggests strongly that the change at codon 245 does represent a heterozygous mutation. Further studies, including the recreation of the mutations, will help to reveal the biochemical consequences resulting from these changes.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1998

Particle polymorphism caused by deletion of a peptide molecular switch in a quasiequivalent icosahedral virus.

The capsid of flock house virus is composed of 180 copies of a single type of coat protein which forms a T=3 icosahedral shell. High-resolution structural analysis has shown that the protein subunits, although chemically identical, form different contacts across the twofold axes of the virus particle. Subunits that are related by icosahedral twofold symmetry form flat contacts, whereas subunits that are related by quasi-twofold symmetry form bent contacts. The flat contacts are due to the presence of ordered genomic RNA and an ordered peptide arm which is inserted in the groove between the subunits and prevents them from forming the dihedral angle observed at the bent quasi-twofold contacts. We hypothesized that by deleting the residues that constitute the ordered peptide arm, formation of flat contacts should be impossible and therefore result in assembly of particles with only bent contacts. Such particles would have T=1 symmetry. To test this hypothesis we generated two deletion mutants in which either 50 or 31 residues were eliminated from the N terminus of the coat protein. We found that in the absence of residues 1 to 50, assembly was completely inhibited, presumably because the mutation removed a cluster of positively charged amino acids required for neutralization of encapsidated RNA. When the deletion was restricted to residues 1 to 31, assembly occurred, but the products were highly heterogeneous. Small bacilliform-like structures and irregular structures as well as wild-type-like T=3 particles were detected. The anticipated T=1 particles, on the other hand, were not observed. We conclude that residues 20 to 30 are not critical for formation of flat protein contacts and formation of T=3 particles. However, the N terminus of the coat protein appears to play an essential role in regulating assembly such that only one product, T=3 particles, is synthesized.

Amino Acid Sequence↗
PubMed2002

Molecular analysis of mutations and polymorphisms of the Lewis secretor type alpha(1,2)-fucosyltransferase gene reveals that Taiwan aborigines are of Austronesian derivation.

The origins of the Taiwan aborigines have not been fully resolved. Anthropological and linguistic studies have indicated that their ancestry is mainly Austronesian or Malayopolynesian. Some polymorphisms and mutations in the secretor type alpha(1,2)-fucosyltransferase (FUT2) gene are found in Taiwan aborigines. In this study, we analyzed the frequency of eight mutations and one polymorphism of the FUT2 gene in Taiwan aborigines and other ethnic groups in order to explore the origins of these groups. The results showed that the C302T, G428A, and fusion gene mutations were specific for Thai, Caucasians, and Japanese, respectively. The A385T mutation was specific for Asians including Taiwan aborigines. The genetic frequencies of C571T were much higher in Taiwan aborigines (1.96% to 20.4%), Filipinos (13.2%), and Indonesians (3.30%) as compared with Thai (0.57%), Chinese (0.65% to 1.12%), Japanese (0%), and Caucasians (0%). The frequencies of the G849A mutation were also higher in Taiwan aborigines (0.38% to 21.57%), Filipinos (6.80%), and Indonesians (1.48%) than in Thai (0.94%), Chinese (0-0.37%), Japanese (0%), or Caucasians (0%). Deletion of a 3-bp region (nt 688 to nt 690) was found only in Filipinos (0.85%), Indonesians (0.74%), and three tribes (0.42% to 2.70%) of Taiwan aborigines, but not in other populations. The C628T mutation was found only in Taiwanese Han, Thai, and two tribes of Taiwan aborigines. The genetic frequency of the C357T polymorphism was much higher in Asians than in Caucasians. The genetic analysis confirms that the origins of Taiwan aborigines are Austronesian and that they are closely related to the Filipino and Indonesian populations. We suggest that mutations or polymorphisms of the FUT2 gene are very good markers for investigating population genetics.

Australia↗
PubMed1993

Direct genotyping and prenatal diagnosis of beta-thalassemia in Chinese by polymerase chain reaction mediated restriction fragment length polymorphism method.

The molecular basis of beta-thalassemia is predominantly point mutations in the beta-globin gene. Frameshift 41-42 (-CTTT), IVS-2 position 654 (C-->T) mutation, nonsense codon 17 (A-->T), TATA box position -28 (A-->G) mutation and frameshift 71-72 (+A) account for more than 95% of beta-thalassemia alleles in the population of South China. We have developed a polymerase chain reaction (PCR)-mediated restriction fragment length polymorphism (RFLP) method for the identification of these alleles. In this method, artificial mispairing bases in PCR-amplified products were created to distinguish normal from mutant alleles on the basis of RFLPs. The size of the five PCR-amplified DNA fragments that may potentially contain the above five types of mutations is 93 or 89 bp (codons 41-42), 221 bp (IVS-2 nt 654), 110 bp (codon 17), 123 bp (TATA box nt -28), and 97 or 98 bp (codons 71-72). After these fragments were digested with Hinc II, Mae III, Nhe I, EcoR I, and Dde I, respectively, the allele-specific RFLPs produced were analyzed by gel electrophoresis. DNA samples of 24 patients with the above five types of beta-thalassemia were investigated with the present method and allele-specific oligonucleotide (ASO) probing simultaneously. We used this method in the prenatal diagnosis of 14 Chinese families for beta-thalassemia. The results obtained by the present method correspond well with those by the ASO probe test.

Adult↗
PubMed2001

[Study on the construction of standard D1S549 allelic ladder via molecular cloning and its genetic polymorphism in Chinese three populations].

OBJECTIVE: To resolve the problem of the accuracy and standardization of STR-PCR typing in forensic practice, we have designed a new method to produce standard D1S549 allelic ladder. METHODS: Eight different PCR amplified D1S549 allelic fragments were isolated from the gel, eluted into the distilled water and re-amplified by PCR. The purified allelic fragments were then blunt-end subcloned individually into the pUC plasmid vectors and transfected into competent E. coli DH5 alpha cells. RESULTS: The sequencing results confirmed that the size and the construe of the inserts were correct. The recombinant plasmids DNA with 8 inserts were then used as templates for re-amplification to generate D1S549 standard ladder, with which the genetic polymorphisms of D1S549 locus in Chinese Han population in chengdu, Hui population in Gansu and Wei population in Xinjiang were studied. CONCLUSION: The results showed that the standard ladder made via this method is excellent, and D1S549 locus is robust for genetic research and forensic application.

Alleles↗
PubMed2025

Evolutionary dynamics and genetic diversity of transposable elements revealed by resequencing data in maize population.

Zea mays (maize) is a globally significant crop with a complex genome enriched with transposable elements (TEs), which are crucial drivers of genomic diversity and plant evolution. In this study, we identified the TE insertion loci (TILs) from resequencing data of 103 maize accessions with the developed pipeline, and 64&#x2009;293 non-redundant unique TILs were obtained in 82 maize accessions after filtering; approximately 80% (51&#x2009;361) of loci showed insertion polymorphisms within the population. All TE superfamilies have low frequency in the maize population except for short interspersed nuclear elements, while some TE families have high fixed TE insertions, revealing distinct evolutionary dynamics among TE superfamilies and families. Genetic analysis using the transposon insertion polymorphism information from the maize population showed that the TE polymorphism loci can reflect their geographical origin and evolutionary relationships. Furthermore, TE insertions could also significantly impact gene expression, implying functional consequences for maize phenotypes and adaptation. These findings provide valuable insights into the evolutionary dynamics and genetic diversity of maize genomes, offering a valuable resource for molecular markers and association studies.

Zea mays↗
PubMed2000

Investigations into the molecular effects of single nucleotide polymorphism.

OBJECTIVES: DNA sequences are very rich in short repeats and their pattern can be altered by point mutations. We wanted to investigate the effect of single nucleotide polymorphism (SNP) on the pattern of short DNA repeats and its biological consequences. METHODS: Analysis of the pattern of short DNA repeats of the Thy-1 sequence with and without SNP. Searching for DNA-binding factors in any region of significance. RESULTS: Comparing the pattern of short repeats in the Thy-1 gene sequences of Turkish patients with ataxia telangiectasia (AT) with the "wild type" sequence from the DNA database, we identified a missing 8-bp repeat element due to an SNP in position 1271 (intron II) in AT-DNA sequences. Only the mutated sequence had the potential for the formation of a stem loop in DNA or pre-mRNA. In super-shift experiments we found that DNA oligomers covering the area of this SNP formed a complex with proteins amongst which we identified the proliferating cell nuclear antigen (PCNA) protein. CONCLUSION: SNPs have the potential to alter DNA or pre-mRNA conformation. Although no SNP-depeding formation of the DNA-protein complex was evident, future investigations could reveal differential molecular mechanisms of cellular regulation.

Ataxia Telangiectasia↗
PubMed1990

Analysis of photoaffinity-labeled aryl hydrocarbon receptor heterogeneity by two-dimensional gel electrophoresis.

The level of charge heterogeneity in the aryl hydrocarbon receptor (AhR) was examined by high-resolution denaturing two-dimensional (2D) gel electrophoresis. Hepa 1c1c7 cell cytosolic fraction was photoaffinity-labeled with 2-azido-3-[125I]iodo-7,8-dibromodibenzo-p-dioxin and applied to isoelectric focusing (IEF) tube gels. After optimization of focusing conditions a broad peak of radioactivity was detected in the apparent pI range of 5.2-5.7. IEF tube gels were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by visualization of the radiolabeled AhR by autoradiography; three distinct isoforms were detected. The same 2D electrophoretic isoform pattern was obtained when the AhR from Hepa 1c1c7 was photoaffinity-labeled in cell culture. BPrCl cells, a mutant line derived from Hepa 1c1c7 cells, contain an AhR that is unable to bind to DNA. Photoaffinity-labeled BPrCl cytosolic fractions were subjected to 2D gel electrophoretic analysis resulting in essentially the same molecular weight and isoform pattern as seen in Hepa 1c1c7 cytosol. This result would suggest that if a mutation is present in the BPrCl AhR it has not caused a significant change in its IEF pattern, although a small shift in the pI values was observed. Two-dimensional gel electrophoresis of photoaffinity-labeled cytosolic fractions from HeLa cells, the rat liver tumor cell line McA-RH7777, and buffalo rat thymus revealed three isoforms, essentially the same isoform pattern as in Hepa 1c1c7 cells. This would indicate that despite the considerable molecular weight polymorphism between species the level of charge heterogeneity is highly conserved.

Affinity Labels↗
PubMed2003

Structure and degree of charge transfer of two polymorphs of a 1:1 molecular complex: [2,2'-bis-1,3-dithiole][9-dicyanomethylene-4,5,7-trinitrofluorene-2-carboxylic acid methyl ester] (TTF-MeDC2TNF).

A new organic charge-transfer complex, C(18)H(7)N(5)O(8).C(6)H(4)S(4), has been prepared using TTF (tetrathiafulvalene) as a donor (D) and MeDC2TNF (9-dicyanomethylene-4,5,7-trinitro-fluorene-2-carboxylic acid methyl ester) as an acceptor (A). Two monoclinic polymorphs of the 1:1 salt were crystallized and characterized by X-ray diffraction. Form alpha crystallizes in space group P2(1)/n with Z' = 1, while form beta crystallizes in space group C2/c with Z' = 1/2 and the MeDC2TNF moiety disordered across a twofold axis. Both phases have mixed-stack crystal packings, which are characteristic of semiconducting one-dimensional organic complexes. However, the observed crystal packings are significantly different, with a single D...A interlayer separation of 3.452 A for the disordered beta polymorph and interlayer separations of 3.378 and 3.483 A in the case of the ordered alpha form. These variations are reflected in the degree of charge transfer, delta, which was estimated on the basis of the b(2u) stretching-mode frequency shift observed in the IR spectra for the cyano groups of the MeDC2TNF radical anion. The fact that the charge transfer is more efficient for alpha-(TTF-MeDC2TNF) than for beta-(TTF-MeDC2TNF) (delta = 0.35 and 0.31, respectively) is consistent with the structural features observed for each crystalline form.

Journal Article↗
PubMed2002

3D model of human arylamine N-acetyltransferase 2: structural basis of the slow acetylator phenotype of the R64Q variant and analysis of the active-site loop.

The human arylamine N-acetyltransferase NAT2 is responsible for the biotransformation of numerous arylamine drugs and carcinogens. A common polymorphism of the NAT2 gene has been associated with susceptibility to drug toxicity and various malignancies. In this study, we used the crystal structure of the Salmonella typhimurium NAT (StNAT) to construct a high-quality model of a catalytic N-terminal region of NAT2 (residues 34-131). We show that this region has a similar structure in StNAT and the human isoforms NAT1 and NAT2. Comparison of the structures of these three molecules suggests that NATs have an active-site loop with a conserved structure, which is involved in substrate recognition. Our model is consistent with previous experimental data and provides the first plausible structural basis of the effects of a common genetic polymorphism (Arg(64)-->Gln) on NAT2 activity.

Acetyl Coenzyme A↗
PubMed1983

The 5'-terminal sequence of TMV RNA. Question on the polymorphism found in vulgare strain.

The complete nucleotide sequence of TMV RNA (common strain) reported in [Proc. Natl. Acad. Sci. USA (1982) 79, 5818] its 5'-end to be represented by two variants which differed in length. We have tested that result and sequenced the 5'-terminal regions of two strains of TMV RNA (common strain OM and tomato strain L) using cloned cDNA copies. The results showed that the 5'-terminal region of the TMV genome is not polymorphic and that one of the two variants cited above represents a tomato strain but not the common strain.

Base Sequence↗
PubMed1989

Identification by sequence analysis of two-site posttranslational processing of the cysteine-rich outer membrane protein 2 of Chlamydia trachomatis serovar L2.

The 60,000-molecular-weight cysteine-rich outer membrane protein (OMP2) from Chlamydia trachomatis participates in the disulfide-mediated outer-membrane organization unique to this organism. In addition, this protein is a primary focus of the host immune response. We cloned and sequenced the gene for OMP2 from C. trachomatis serovar L2. A lambda gt11 recombinant that expressed an antigenic portion of this protein was selected by antibody screening and provided a probe for the selection in lambda 1059 of a clone containing the entire gene. DNA sequencing of this clone identified one open reading frame of 1,641 base pairs, starting with a methionine codon and coding for a polypeptide with a molecular weight of 58,792. Amino-terminal protein sequencing and analysis of the translated DNA sequence demonstrated that processing at alternate signal peptide cleavage sites accounts for the molecular-weight polymorphism of this protein. The mature proteins had a net positive charge and contained 24 cysteine residues.

Amino Acid Sequence↗
PubMed1991

The structure of human MHC class II genes.

The class II molecules of the human major histocompatibility complex bind intracellularly processed peptides and present them to T-helper cells. They therefore have a critical role in the initiation of the immune response. A salient feature of the class II molecules is their polymorphism. It has been shown that some autoimmune diseases are associated with certain class II alleles. This article reviews the basic structural features of class II molecules, and the genes encoding them as well as mechanisms governing the development of their extraordinary polymorphism.

Autoimmune Diseases↗
PubMed2001

Trinucleotide (CAG) repeat polymorphisms in the androgen receptor gene: molecular markers of risk for male infertility.

OBJECTIVE: To determine whether changes in the polymorphic trinucleotide (CAG) tract of the androgen receptor gene are associated with spermatogenic defects in patients with male infertility. DESIGN: Case-control study of two ethnic groups. SETTING: University referral centers for male infertility at Baylor College of Medicine, Houston, Texas, and National University Hospital, Singapore. PARTICIPANT(S): Two hundred and fifteen patients with male infertility and depressed spermatogenesis and 142 fertile controls. MAIN OUTCOME MEASURE(S): Size of androgen receptor CAG alleles according to fluorescent-labeled polymerase chain reaction and automated analysis using Genescan software (PE Biosystems Asia, Singapore), and statistical examination of its relation to clinical variables. RESULT(S): In U.S. patients, the mean androgen receptor CAG length was significantly longer in infertile patients than in fertile controls (21.95 +/- 0.31 vs. 20.72 +/- 0.52). Logistic regression showed that each unit increase in CAG length was associated with a 20% increase in the odds of being azoospermic. The odds ratio for azoospermia was sevenfold higher for patients with > or =26 CAG repeats than in those with <26 CAG repeats. Although mean CAG length in Singapore patients was longer than in the U.S. samples, long androgen receptor CAG alleles were significantly related to male infertility in both populations. CONCLUSION(S): Long (> or =26) androgen receptor CAG alleles, which are found in up to 25% of azoospermic men, are associated with male infertility and defective spermatogenesis. Conception in these men is possible with assisted reproductive technologies, as many have spermatozoa in their testes.

Biopsy↗
PubMed2005

VariScan: Analysis of evolutionary patterns from large-scale DNA sequence polymorphism data.

SUMMARY: VeriScan is a software package for the analysis of DNA sequence polymorphisms at the whole genome scale. Among other features, the software (1) can conduct many population genetic analyses; (2) incorporates a multiresolution wavelet transform-based method that allows capturing relevant information from DNA polymorphism data; (3) facilitates the visualization of the results in the most commonly used genome browsers.

Algorithms↗