SEARCH · Search PubMed

Results for “synonymous variant”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

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

At least 289 records · Page 16Linked to original sources

PubMedDate not supplied

Isolation of major histocompatibility complex class I cDNA from pink salmon (Oncorhynchus gorbuscha).

An MHC class I cDNA clone was isolated from pink salmon (Oncorhynchus gorbuscha). Eight amino acids, which have been shown in mammals to bind main-chain atoms of peptides, are well conserved in the salmon alpha 1 and alpha 2 domains. Nine amino acids in the alpha 3 domain are classified by Williams and Barclay (Ref. 1. Ann. Rev. Immunol. 6:381-405, 1988) as signature immunoglobulin superfamily residues. The pink salmon MHC class I extracellular domains show 84.2% amino acid identity with those of Atlantic salmon (Sasa p30). polymorphism of the MHC class I alpha 1 domain was determined using PCR with genomic DNA from 12 fish. Sixteen variants were identified with most diversity concentrated in those amino acids that bind directly to peptides in mammalian class I molecules. Non-synonymous substitutions predominate over synonymous ones in the codons encoding these polymorphic residues.

Amino Acid Sequence↗

PubMed2006

Allelic variation of the ovine Toll-like receptor 4 gene.

The family of Toll-like receptors (TLRs) is responsible for recognition of pathogen-associated molecular patterns (PAMPs), and Toll-like receptor 4 (TLR4) recognizes not only exogenous ligands such as the lipopolysaccharide (LPS) of Gram-negative bacteria, but also a number of endogenous ligands. Variation in the nucleotide sequence of the ovine TLR4 gene was investigated by amplification of a fragment containing a putative ligand-binding region using polymerase chain reaction (PCR), followed by single-strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. Four novel SSCP patterns, representing four different sequences, were identified. Either one or two different sequences were detected in individual sheep and all the sequences identified shared high homology to the TLR4 sequences from a variety of species, suggesting that these sequences represent allelic variants of the ovine TLR4 gene. Fourteen single nucleotide polymorphisms (SNPs) were detected, and 79% (11 of 14) of SNPs were non-synonymous substitutions that would result in amino acid changes. Variation detected here might have an impact on pattern recognition and hence affect the immune response to pathogens.

Alleles↗

PubMed2003

Extent of mitochondrial DNA sequence variation in Atlantic cod from the Faroe Islands: a resolution of gene genealogy.

Variation in a 250 base pair (bp) fragment of the mitochondrial cytochrome b (cyt b) has been used extensively for population studies in Atlantic cod Gadus morhua. To study the shape of the gene genealogy and the nature of the polymorphism, sequences of another region of the cyt b gene and the TP intergenic spacer were added, making a total of 566 bp from 74 cod from the Faroe Islands. A total of 44 segregating sites defined 41 haplotypes, many at frequencies greater than 5%. Haplotype diversity was 0.97 and nucleotide diversity 0.73% per base. A topology referred to as a constellation gene genealogy was observed with four major haplotypes at high frequencies, from each of which a number of rare variants were derived. A young relative age of the haplotypes was gauged from the structure of the genealogy. The variation was mostly at synonymous sites within the coding region and thus likely to be neutral or under weak purifying selection. By comparative analysis this also applies to the TP spacer. Applying the locus to study population variation in the Faroe Islands by AMOVA revealed that the overall areas and localities within areas accounted for none of the variation, and all the variation was due to differences among individuals.

Alleles↗

PubMed2005

Synonymous mutations in CFTR exon 12 affect splicing and are not neutral in evolution.

It is well established that exonic sequences contain regulatory elements of splicing that overlap with coding capacity. However, the conflict between ensuring splicing efficiency and preserving the coding capacity for an optimal protein during evolution has not been specifically analyzed. In fact, studies on genomic variability in fields as diverse as clinical genetics and molecular evolution mainly focus on the effect of mutations on protein function. Synonymous variations, in particular, are assumed to be functionally neutral both in clinical diagnosis and when measuring evolutionary distances between species. Using the cystic fibrosis transmembrane conductance regulator (CFTR) exon 12 splicing as a model, we have established that about one quarter of synonymous variations result in exon skipping and, hence, in an inactive CFTR protein. Furthermore, comparative splicing evaluation of mammalian sequence divergences showed that artificial combinations of CFTR exon 12 synonymous and nonsynonymous substitutions are incompatible with normal RNA processing. In particular, the combination of the mouse synonymous with the human missense variations causes exon skipping. It follows that there are two sequential levels at which evolutionary selection of genomic variants take place: splicing control and protein function optimization.

Amino Acid Sequence↗

PubMed2005

High genetic variability and evidence for plant-to-plant transfer of Banana mild mosaic virus.

A total of 154 partial nucleotide sequences within the Banana mild mosaic virus (BanMMV) ORF1, which encodes the viral RNA-dependent RNA polymerase (RdRp), was obtained from 68 distinct infected banana accessions originating from various locations worldwide. The 310 nt sequences displayed a high level of variability with a mean pairwise nucleotide sequence divergence level of 20.4 %. This situation resulted essentially from a high rate of synonymous mutations. A similar analysis was performed for a limited selection of 10 banana accessions (30 sequences) on the region comprising approximately the last 310 nt of the BanMMV genome. This region corresponds to the 3' end of ORF5, which encodes the coat protein (234 nt), and to the 3' non-coding region. This analysis confirmed the high level of diversity observed in the RdRp dataset, characterized by a high level of synonymous mutations. Analysis of intra-host diversity indicated the existence of two distinct situations, with some plants containing only closely related sequence variants, whereas others contained widely divergent isolates. Analyses indicated that BanMMV genetic diversity is not structured by the geographical origin of the infected Musa accessions or by their genotype. This situation may be, in part, explained by the exchange of banana germplasm between different parts of the world and also by plant-to-plant transfer of virus isolates, the evidence for which is, for the first time, provided by this study.

Base Sequence↗

PubMed2006

Genetic variability of human cytomegalovirus UL132 gene in strains from infected infants.

Human cytomegalovirus (HCMV) displays genetic polymorphisms. HCMV infects a number of organs and cell types, leading to the hypothesis that HCMV disease and tissue tropism may be related to specific sequence variability. A gene in UL/b' of HCMV, UL132 open reading frame (ORF), encodes glycoprotein (gpUL132) which is identified as a low-abundance structural component of HCMV. In this study, the sequence variability of the UL132 gene was studied in 30 clinical strains. The results showed that a large number of nucleotide non-synonymous substitutions occurred in the UL132 ORF, particularly in the 5' half, in comparison to the UL132 of reference strain, Toledo. The UL132 variants of the clinical strains were clustered clearly into three major groups in the phylogenetic tree: G1(10/30), G2(9/30), and G3(11/30). The precise definition of UL132 genotypes and their putative functions would be helpful in a better understanding of the HCMV.

Amino Acid Sequence↗

PubMed1992

[The P300 component of the event-related brain potential in a short-term memory paradigm].

In numerous investigations the P300-component of the event-related-brain-potential (ERP) has proved a valid indicator of memory activities. The present study explores the amplitude of the P300 in an isolated short term memory task with variant difficulties. In two experiments the reproduction of senseless memory material was examined using the categories "syllables" and "consonants". One syllable was thereby synonymous with the so-called "chunk" which represents a subjective unit arising from grouping of memory material. The results show a significant increase in P300-amplitude in a line with memory load in both categories. On the contrary there is no significant difference in the amplitude of P300 between the two categories. These results suggest that the costs for storing one syllable are comparable with those for one consonant.

Adult↗

PubMed2006

Expression and diversity of Echinococcus multilocularis AgB genes in secondarily infected mice: evaluating the influence of T-cell immune selection on antigenic variation.

The T-cell-mediated immune response exhibits a crucial function in the control of the intrahepatic proliferation of Echinococcus multilocularis larvae in mice and humans, both being natural intermediate hosts of the parasite. Antigen B (AgB), a metabolized Echinococcus spp. lipoprotein, contributes to the modulation of the T-cell immune response, and distinct sites of the corresponding AgB1, AgB3 and AgB4 genes were shown to be under positive selection pressure. Since several AgB gene variants are present in a single Echinococcus metacestode, we used secondary E. multilocularis infections in BALB/c and in athymic nude mice (devoid of T-cell responses) to analyze the effect of the cellular immune response on the expression and diversity of EmAgB1-EmAgB4 genes. We demonstrated hereby that EmAgB transcripts were less abundant in nude mice during the early phase of infection (at one month post-infection), and that EmAgB2 is simultaneously down-regulated when compared to the other three genes. A negative relationship exists between the level of transcription and diversity of EmAgB genes. Moreover, no excess of non-synonymous substitutions was found among the distinct EmAgB alleles from a single host. Together, these results pointed to the effect of purifying selection, which seemed to eliminate the detrimental AgB variants generated during the development of the metacestode within the peritoneal cavity of its intermediate host.

Animals↗

PubMed2003

A haplotype-based molecular analysis of CFTR mutations associated with respiratory and pancreatic diseases.

Aberrant membrane transport caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is associated with a wide spectrum of respiratory and digestive diseases as well as cystic fibrosis. Using a gene scanning method, we found 11 polymorphisms and mutations of the CFTR gene in the Korean population. Individual variants at these sites were analyzed by conventional DNA screening in 117 control and 75 patients having bronchiectasis or chronic pancreatitis. In a haplotype determination based on a Bayesian algorithm, 15 haplotypes were assembled in the 192 individuals tested. Several haplotypes, especially with Q1352H, IVS8 T5, and E217G, were found to have disease associations in a case-control study. Notably, a common polymorphism of M470V appears to affect the intensity of the disease association. Among the two haplotypes having IVS8 T5, the T5-V470 haplotype showed higher disease association than the T5-M470 haplotype. In addition, a Q1352H mutation found in a V470 background showed the strongest disease association. The physiological significances of the identified mutations were rigorously analyzed. Non-synonymous E217G and Q1352H mutations in the M470 background caused a 60-80% reduction in CFTR-dependent Cl(-) currents and HCO3(-) -transport activities. Surprisingly, the additional M470V polymorphic variant with the Q1352H mutation completely abolished CFTR-dependent anion transport activities. These findings provide the first evidence on the importance of CFTR mutations in the Asian population. Importantly, the results also reveal that interactions between multiple genetic variants in cis affect the final function of the gene products.

Alleles↗

PubMed2003

Genetic variation of varicella-zoster virus: evidence for geographical separation of strains.

Heteroduplex mobility assay was used to identify variants of varicella-zoster virus (VZV) circulating in the United Kingdom and elsewhere. Forty variable positions were identified. Sixteen substitutions were non-synonymous, resulting in an amino acid change, the majority of which were clustered within surface expressed proteins. Phylogenetic analysis distinguished at least three major clades (strains A, B, C) supported by significant bootstrap values. Apart from the United Kingdom and Brazil where all three strains were found, genotypes appeared to be closely associated with the geographical region in which they were sampled. Allelic co-segregation of widely spaced single nucleotide polymorphisms (SNPs) confirmed the genetic stability of the VZV. Recombination rates were difficult to calculate because of the low intra genotypic variation. However, one haplotype originating from Brazil is most parsimoniously explained as a recombinant between A and C strains, which co-occur in the region. Two further UK strains appeared to be recombinants between groups B and C.

Africa↗

PubMed2003

Failure to find causal mutations in the GABA(A)-receptor gamma2 subunit (GABRG2) gene in Japanese febrile seizure patients.

Recently, mutations in the GABA(A)-receptor gamma2 subunit (GABRG2) gene were identified in two families with generalized epilepsy with febrile seizures plus (GEFS+) and two families with childhood absence epilepsy (CAE) and febrile seizures (FS). We tested the hypothesis that genetic variations in the GABRG2 gene confer susceptibility to FS in the Japanese population. We performed a systematic search for mutations in 94 unrelated Japanese patients with FS and detected six variants (-158C>T, 315C>T, 588T>C, IVS5-55C>T, IVS7+20G>A, and IVS7-141T>A). No non-synonymous mutation was detected. We genotyped three exonic polymorphisms and performed a case control study and a transmission disequilibrium test using 55 independent complete trios with FS and 106 control subjects. None of these polymorphic alleles were significantly associated with FS. Our results indicate that genomic variations of GABRG2 are not likely to be substantially involved in the etiology of FS in the Japanese population.

Alleles↗

PubMed2006

Sequence analysis of the genes encoding for H+/K+-ATPase in autoimmune gastritis.

BACKGROUND: H+/K+-ATPase is the target autoantigen in autoimmune gastritis (AIG), an organ-specific autoimmune disease with a strong hereditary component. AIM: To detect possible polymorphisms in H+/K+-ATPase alpha- and beta-subunits in AIG patients. METHODS: Blood samples from 12 Finnish AIG patients were sequenced for the coding regions of genes encoding for H+/K+-ATPase alpha- and beta-subunits; 50-52 Finnish anonymous blood donors served as controls. Additionally, parietal cell and Helicobacter pylori antibodies and serum pepsinogen I levels (PG I) were analysed. RESULTS: In the alpha-subunit, all patients and controls had C-allele at the non-synonymous c.824T>C single nucleotide polymorphism (SNP) resulting in valine substitution for alanine (Val265Ala). In the beta-subunit, a previously unknown non-synonymous SNP resulting in a substitution of alanine residue for valine (Ala248Val) was found in exon 7 in a single patient and none of the controls. All patients had low serum PG I levels and elevated parietal cell antibodies; three had positive H. pylori serology. CONCLUSIONS: At the non-synonymous SNP c.824T>C in the alpha-subunit of H+/K+-ATPase most Finnish individuals with or without AIG have C allele. Genetic variants of the coding regions of genes for H+/K+-ATPase alpha- and beta-subunits are not associated with AIG in Finnish patients.

Adult↗

PubMed2006

Gene for the serotonin transporter and ADHD: no association with two functional polymorphisms.

Evidence from both human and animal studies implicates the serotonergic system in the development of attention-deficit hyperactivity disorder (ADHD) including positive association studies for several key serotonergic genes. The serotonin transporter (HTT) regulates the availability of serotonin by reuptake of the neurotransmitter from the synaptic cleft. Several studies have reported an association of this gene to ADHD, specifically the long variant of a common insertion/deletion polymorphism located in the promoter of this gene that results in increased transcription and higher HTT expression. An additional study found no evidence for an association with this polymorphism. Recently, an A/G single nucleotide polymorphism (SNP) was found within the promoter polymorphism with functional studies indicating that the long variant containing the G allele at this site behaves like the short variant. This previously unidentified functional change may have confounded earlier association studies. We investigated the relationship of several variants to ADHD: the promoter polymorphisms, SNP in the 3' untranslated region (3'UTR) with a reported association to ADHD and a rare, non-synonymous coding SNP. These polymorphisms were genotyped in 209 ADHD families identified through an affected proband. We did not find evidence for an association of these polymorphisms, or haplotypes of these polymorphisms, to ADHD in this sample.

Adolescent↗

PubMed2002

Simultaneous detection of six citrus viroids and Apple stem grooving virus from citrus plants by multiplex reverse transcription polymerase chain reaction.

We developed a multiplex reverse transcription polymerase chain reaction (RT-PCR) to detect six citrus viroids: Citrus exocortis viroid (CEVd), Citrus bent leaf viroid (CBLVd), Hop stunt viroid (HSVd), Citrus viroid III (CVd-III), Citrus viroid IV (CVd-IV) and Citrus viroid OS (CVd-OS) and Apple stem grooving virus (ASGV, synonym: Citrus tatter leaf virus (CTLV)) from citrus plants. The multiplex RT-PCR was also designed to distinguish CVd-I-LSS (a distinct variant of CBLVd) from CBLVd. By the multiplex RT-PCR, one to eight fragments specific to the pathogens were simultaneously amplified from one sample and identified by their specific molecular sizes in 6% polyacrylamide gel electrophoresis. The results of the multiplex RT-PCR were consistent with those of other diagnoses, such as uniplex RT-PCR, to detect each of the pathogens. The multiplex RT-PCR provides a simple and rapid method for detecting various viroids and ASGV in citrus plants, which will help diagnose many citrus plants at a time.

Citrus↗

PubMed2000

The erythrocyte binding motif of plasmodium vivax duffy binding protein is highly polymorphic and functionally conserved in isolates from Papua New Guinea.

The Duffy binding protein (DBP) of Plasmodium vivax is a critical adhesion ligand that participates in merozoite invasion of human Duffy positive reticulocytes. Binding domains have been shown to lie within a conserved N-terminal cyteine-rich region, region II, that contains 330-aa and the critical binding residues have been recently mapped to 170-aa stretch within this region. Previous studies on few isolates indicated a significant degree of polymorphism in region II (DBPII). To examine further the degree of variability of DBPII, and whether these variants produce functional changes, DBPII was amplified by nested PCR from 24 isolates from Papua New Guinea, and the amplicons were cloned and sequenced. One synonymous and 18 non-synonymous mutations were identified. Altogether, 93% of the cumulative polymorphisms lie within the 170-aa region. Targeted surface expression of region II of two different alleles on the surface of Cos7 cells did not affect their binding to Duffy positive erythrocytes. These results indicate that polymorphisms in the critical binding motifs do not alter its function. If DBPII variation arose to avert mechanisms of protective immunity targeting the DBP, vaccine development employing the parasite binding ligand may require strategies to minimize the effect of this polymorphism.

Adult↗

PubMed2001

[The history of Schimmelbusch's disease].

In 1982, Curt Schimmelbusch published a paper named "Cystadenoma of the breast", describing the clinical & pathological criteria of Schimmelbusch's disease. For many years this condition was one variant of fibrocystic mastopathy. Today, Schimmelbuuschs disease can be classified as part of ANDI-Aberration of normal development and iInvolution, The histopathological description is synonymous to adenosis. This is a short survey of the history of Schimmelbusch's Disease.

Breast Diseases↗

PubMed2006

Allelic variants of SCN5A and risk of sudden cardiac arrest in patients with coronary artery disease.

BACKGROUND: Most sudden cardiac arrests occur in patients who have associated significant coronary artery disease (CAD), but current methods of risk stratification are inadequate. OBJECTIVES: The purpose of this study was to evaluate whether allelic variation of SCN5A could determine risk of sudden cardiac arrest among patients with CAD. METHODS: This case-control study was conducted as part of the ongoing Oregon Sudden Unexpected Death Study (Ore-SUDS). Cases of sudden cardiac arrest with associated CAD were identified among residents of Multnomah County, Oregon (population 660,486). Geographically matched control subjects had significant CAD but no history of cardiac arrest, ventricular arrhythmia, or syncope. DNA was extracted from blood samples, and all 28 exons of SCN5A were screened for allelic variants using denaturing high-performance liquid chromatography. All identified variants were confirmed by direct sequencing. RESULTS: Sixty-seven cases (mean age 65 +/- 13 years, 18% female) and 91 controls (mean age 66 +/- 12 years, 30% female) were compared. Race was known in 94% of all patients; 92% of case subjects and 89% of control subjects were Caucasian. No patient had clinically manifest familial long QT syndrome. Nonsynonymous nucleotide changes were found in 4% of cases and 1% of controls (P = .31), with one novel mutation (G1291A) identified in one case subject. Synonymous nucleotide changes were found in 27% of cases and 21% of controls (P = .45). CONCLUSION: The overall prevalence of amino acid-altering polymorphisms of the SCN5A gene was relatively low in both groups. Allelic variants of SCN5A did not contribute to risk of sudden cardiac arrest in this primarily Caucasian population with significant CAD.

Aged↗

PubMed1983

Miltenberger Class I and II erythrocytes carry a variant of glycophorin A.

The membranes from Miltenberger Class I (Mi I) and II (Mi II) erythrocytes, two rare variants at the blood group MNSs locus, exhibited an abnormal glycoprotein of 32 kDa apparent molecular mass sharply stained by the periodic acid/Schiff procedure and a decreased content of glycoprotein alpha (synonym glycophorin A, glycoprotein MN) as seen on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Purified 125I-labelled Vicia graminea lectin binds to the unusual 32 kDa glycoprotein separated from Mi I and Mi II erythrocyte membrane of blood group NN or MN, but no significant labelling of this band was observed with Mi samples typed MM. On the basis of such lectin-labelling experiments we have described two heterozygous MN, Mi I individuals that carry one copy of an M gene producing a normal alpha-glycoprotein with M-specificity and one copy of a MiI gene producing a 32 kDa glycoprotein with N-specificity. Further investigations have shown that the 32 kDa glycoprotein was immunoprecipitated by two mouse monoclonal antibodies (R18 and R10) reacting specifically with the external domain of glycoprotein alpha. These results demonstrate that Mi I and Mi II erythrocytes carry an unusual variant of glycoprotein alpha.

Antibodies, Monoclonal↗