Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Variant identification”

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.

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

At least 1,045 records · Page 58Linked to original sources
PubMed1998

High-throughput screening for known mutations by automated analysis of single sequencing reactions.

This work shows that single sequencing reactions analyzed on an automated DNA sequencer can be an efficient way of screening PCR products for known mutations. We have analyzed a mutation in exon 10 of the human aromatase gene and show that an unambiguous genotype could be elucidated in more than 90% of the analyzed samples. Compared to analysis by full sequencing, 4 times more samples can be analyzed per gel, so that the sample capacity of the gel is approaching that of alternative gel-based methods for genotype analysis. Unlike many of these, the method offers direct identification of the variant sequence position and on-line analysis without the need of post-electrophoretic processing of the gel.

Aromatase↗
PubMed2004

Genetic variation and lactose intolerance: detection methods and clinical implications.

The maturational decline in lactase activity renders most of the world's adult human population intolerant of excessive consumption of milk and other dairy products. In conditions of primary or secondary lactase deficiency, the lactose sugars in milk pass through the gastrointestinal tract undigested or are partially digested by enzymes produced by intestinal bacterial flora to yield short chain fatty acids, hydrogen, carbon dioxide, and methane. The undigested lactose molecules and products of bacterial digestion can result in symptoms of lactose intolerance, diarrhea, gas bloat, flatulence, and abdominal pain. Diagnosis of lactose intolerance is often made on clinical grounds and response to an empiric trail of dietary lactose avoidance. Biochemical methods for assessing lactose malabsorption in the form of the lactose breath hydrogen test and direct lactase enzyme activity performed on small intestinal tissue biopsy samples may also be utilized. In some adults, however, high levels of lactase activity persist into adulthood. This hereditary persistence of lactase is common primarily in people of northern European descent and is attributed to inheritance of an autosomal-dominant mutation that prevents the maturational decline in lactase expression. Recent reports have identified genetic polymorphisms that are closely associated with lactase persistence and nonpersistence phenotypes. The identification of genetic variants associated with lactase persistence or nonpersistence allows for molecular detection of the genetic predisposition towards adult-onset hypolactasia by DNA sequencing or restriction fragment length polymorphism analysis. The role for such genetic detection in clinical practice seems limited to ruling out adult-onset hypolactasia as a cause of intolerance symptoms but remains to be fully defined. Attention should be paid to appropriate interpretation of genetic detection in order to avoid potentially harmful reduction in dairy intake or misdiagnosis of secondary lactase deficiency.

Adult↗
PubMed2004

PorA variable regions of Neisseria meningitidis.

Subtypes, defined by variation in the outer membrane protein PorA, are an integral part of the characterization scheme for Neisseria meningitidis. Identification of these variants remains important as the PorA protein is a major immunogenic component of several meningococcal vaccines under development, and characteristics of PorA are used to provide detailed epidemiologic information. Historically, serosubtypes have been defined by reactivity with a set of monoclonal antibodies. However, nucleotide sequence analyses of porA genes have established that the panel of serosubtyping monoclonal antibodies is not exhaustive, and many porA variants cannot be detected. In addition, the nomenclature system used to define subtypes is inadequate. We examined all available nucleotide sequences of the porA VR1 and VR2 regions to identify and define subtype families. A revised nomenclature scheme, compatible with the previous serologic nomenclature scheme, was devised. A Web-accessible database describing this nomenclature and its relationship to previous schemes was established (available from: http://neisseria.org/nm/typing/pora).

Amino Acid Sequence↗
PubMed2004

Toxic cyanobacteria strains isolated from blooms in the Guadiana river (southwestern Spain).

This paper describes the occurrence of toxic cyanobacteria along the Guadiana River over its course between Mérida and Badajoz (Extremadura, Spain). Water sampling for phytoplankton quantification and toxin analysis was carried out regularly between 1999 and 2001 in six different locations, including two shallow, slow-flowing river sites, two streamed river sites and two drinking water reservoirs. The cyanobacterial community differed significantly between these locations, especially during the summer. The predominant genera were Microcystis, Oscillatoria, Aphanizomenon and Anabaena. Using an ELISA assay the total microcystin contents of natural water samples from the most eutrophic locations ranged from 0.10 - 21.86 microg mcyst-LR equivalent x L(-1) in Valdelacalzada and 0.10-11.3 microg mcyst-LR equivalent x L(-1) in Vitonogales, and a seasonal variation of toxin content was observed. The amount of microcystins produced by each strain was determined by ELISA assay and the detection and identification of microcystin variants of three toxic strains of Microcystis aeruginosa was performed by high performance liquid chromatography (HPLC). The analysis of microcystins of the cultured strains revealed that toxin production was variable among different strains of M. aeruginosa isolated either from different blooms or from the same bloom.

Animals↗
PubMed1991

Anthracycline metabolites from Streptomyces violaceus A262. I. Isolation of antibiotic-blocked mutants from Streptomyces violaceus A262.

Five mutant (or variant) strains producing new anthracycline antibiotics were derived from Streptomyces violaceus A262 by mutagenesis treatment. Strain SE1-625 showed a limited production of three known beta-rhodomycinone diglycosides while the parent strain produced numerous unidentified beta-rhodomycinone glycosides. Strain SU2-730 was an antibiotic-blocked mutant which produced only epsilon-rhodomycinone glycosides (named epelmycins). Strains SC-7 and SE2-2385 were variants which produced alpha-citromycinone glycosides (named yellamycins) and beta-isorhodomycinone glycosides (named obelmycins), respectively. Strain SE2-2385-A1 produced alpha 2-rhodomycinone glycosides (named alldimycins). Glycosidation-less mutants which accumulated only aglycone were also obtained. Isolation of these mutants or variants and preliminary identification of their anthracycline products are described.

Anthracyclines↗
PubMed1999

An approach to optimizing the active site in a glutathione transferase by evolution in vitro.

A glutathione transferase (GST) mutant with four active-site substitutions (Phe(10)-->Pro/Ala(12)-->Trp/Leu(107)-->Phe/Leu(108)-->Arg) (C36) was isolated from a library of active-site mutants of human GST A1-1 by the combination of phage display and mechanism-based affinity adsorption [Hansson, Widersten and Mannervik (1997) Biochemistry 36, 11252-11260]. C36 was selected on the basis of its affinity for the transition-state analogue 1-(S-glutathionyl)-2,4, 6-trinitrocyclohexadienate. C36 affords a 10(5)-fold rate enhancement over the uncatalysed reaction between reduced glutathione and 1-chloro-2,4-dinitrobenzene (CDNB), as evidenced by the ratio between k(cat)/K(m) and the second-order rate constant k(2). The present study shows that C36 can evolve to an even higher catalytic efficiency by an additional site-specific mutation. Random mutations of the fifth active-site residue 208 allowed the identification of 18 variants, of which the mutant C36 Met(208)-->Cys proved to be the most active form. The altered activity was substrate selective such that the catalytic efficiency with CDNB and with 1-chloro-6-trifluoromethyl-2,4-dinitrobenzene were increased 2-3-fold, whereas the activity with ethacrynic acid was decreased by a factor of 8. The results show that a single-point mutation in the active site of an enzyme may modulate the catalytic activity without being directly involved as a functional group in the enzymic mechanism. Such limited modifications are relevant both to the natural evolution and the in vitro redesign of proteins for novel functions.

Amino Acid Substitution↗
PubMed2000

The persistent stapedial artery.

The persistent stapedial artery is a rare congenital vascular anomaly that may present as a pulsatile middle ear mass or that may appear as an incidental finding. Five cases of persistent stapedial artery are presented. The CT findings include the absence of the ipsilateral foramen spinosum and a soft-tissue prominence in the region of the tympanic segment of the facial nerve. Three cases were associated with an aberrant internal carotid artery. Imaging identification of this variant may obviate unnecessary surgery and may help in planning surgical or endovascular interventions.

Adolescent↗
PubMed1977

[Genetic heterogeneity of G6PD deficiency: mutant alleles of G6PD in the Shekii district of Azerbaijan].

Examination on G6PD deficiency in 349 patients of Shekii district hospital (Azerbaijan) revealed 16 hemi-, 4 homo- and 9 heterozygotic carriers of the defect. Gd- frequency, calculated from the data obtained (7.7%), may be compared to neighbouring regions' frequencies (6-30%). Carriers of G6PD deficiency are residents of 11 villages located in Alasani-Aphtalan valley, highly endemic with malaria in the past; nearly all marriages are endogamic. Physico-chemical and kinetic study of 10 mutant forms of G6PD, according to WHO program, led to identification of 5 variants of the II class (Shekii, Bideiz, Shirin-Bulakh, Okhut I and Zakataly) and 2 variants of the III class (Okhut II and Martinique-like). Resemblance of the majority of variants in electrophoretic mobility and the level of erythrocyte enzyme activity permit to suggest the existence of a common parental mutant G6PD allele distributed in this area.

Alleles↗
PubMed2004

ERCC2 genotypes and a corresponding haplotype are linked with breast cancer risk in a German population.

The polygenic concept of breast cancer susceptibility calls for the identification of genetic variants that contribute to breast cancer risk. Reduced DNA repair proficiencies in women with breast cancer pointed to a possible role of DNA repair enzymes in the risk to develop the disease. The nucleotide excision repair enzyme encoded by the excision repair cross-complementing group 2 gene ERCC2 (formerly XPD) known to cause skin cancer by germ line mutations has multiple regulatory cellular functions, including nucleotide excision repair, basal transcription, cell cycle control, and apoptosis. ERCC2 polymorphisms ERCC2_6540_G>A (Asp(312)Asn) and ERCC2_18880_A>C (Lys(751)Gln) within the coding region of this evolutionarily highly conserved gene have been of functional relevance and therefore are potential candidates to confer breast cancer susceptibility. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we analyzed genotype frequencies in constitutional DNA of study participants of a German case-control study that included 688 cases of incident breast cancer and 724 population-based, age-matched controls. We identified ERCC2_6540_GG (Asp(312)Asp) as an at-risk genotype [odds ratio (OR), 2.06; 95% confidence interval (95% CI), 1.39-3.07]. The ERCC2_6540_GG-associated breast cancer risk was even higher in women who were also carriers of the ERCC2_18880_CC (Gln(751)Gln) genotype (OR, 3.69; 95% CI, 1.76-7.74). We identified ERCC2_6540_G/ERCC2_18880_C (Asp(312)/Gln(751)) as the most potent risk-conferring haplotype (OR, 3.49; 95% CI, 2.30-5.28). To our knowledge, this is the first study assigning breast cancer risk to both the ERCC2 genotype encoding Asp(312)Asp and the haplotype encoding Asp(312)/Gln(751).

Adult↗
PubMed1991

[The course of dilated cardiomyopathy (long-term follow-up data)].

A long-term (1-8 years) prospective follow-up of 224 patients with dilated cardiomyopathy permitted identification of 3 variants of the disease run: benign (9.4%), protracted (51.8%) and malignant (38.8%). These variants are characterized by different gravity and time course changes in cardiovascular function and pumping capacity affections, in hypertrophy of the cardiac muscle, in incidence rate, time and causes of lethal outcomes.

Adolescent↗
PubMed1991

[New data concerning the etiology of insulin-dependent diabetes].

The mechanism of pancreatic beta-cell destruction in type I (insulin-dependent) diabetes mellitus (IDDM) involves autoimmune events directed against these cells. Anti-beta-cell autoimmunity occurs in genetically predisposed individuals and may precede clinical manifestations of IDDM by several years. Markers for beta-cell autoimmunity, especially islet-cell antibodies, are being used with increasing reliability both for detection of IDDM and for evaluating the risk of development of the disease. HLA alleles associated with IDDM include DR3 and DR4, with the risk of IDDM being especially high in individuals with the heterozygous combination DR3/DR4. Recent advances in molecular biology have resulted in more accurate identification of genetic variants and even of amino acid sequences associated with IDDM. These markers can be used to identify patients with genetic susceptibility to the disease. The mechanism of action of genes associated with IDDM is as yet unknown but probably involves the receptor function of HLA molecules for antigens during immune responses.

Autoimmune Diseases↗
PubMed1985

[Isolation of a plasmid from actinomycin C-producing Streptomyces chrysomallus and its characteristics].

Until now the identification of plasmids in streptomyces, the producers of actinomycins, has not been reported, although there exist the genetic data on the possible plasmid participation in biosynthesis of these antibiotics. In this paper the data are presented on plasmid identification in two variants of Streptomyces chrysomallus. Plasmids are shown to be identical in both variants differing in productiveness. The restriction map is constructed for this 7000 b. p. plasmid. Plasmid participation in actinomycin biosynthesis and its possible use for molecular cloning in streptomyces are discussed.

DNA Restriction Enzymes↗
PubMed1987

Human immunodeficiency virus and related retroviruses.

This paper summarizes the current knowledge on the human immunodeficiency virus (HIV) and related retroviruses, describing basic characteristics of this new group of viruses such as morphologic and genetic structure, biological and cultural properties, virus growth characteristics, genetic variability and virus replication. The discovery of new human and simian retroviruses has prompted the World Health Organization (WHO) to convene a group of experts to establish criteria for their characterization. This will allow rapid identification of new variants that may arise and allow public health measures to be implemented accordingly. Different approaches are made to nomenclature in view of the evolution of knowledge about these viruses, and a system of nomenclature has been proposed by the WHO working group. This system, inspired by the one developed for the influenza viruses, is practical and descriptive, providing information on the origins of the organism and its type.

Deltaretrovirus↗
PubMed1988

[Recent progress in the biology of small cell bronchial carcinoma].

Progress achieved in the understanding of small cell lung cancer (SCLC) include: the establishment and characterization of cell lines with the identification of a variant type with poor prognosis; the use of non-specific biochemical markers such as neuron specific enolase (NSE) and calcitonin; the generation of monoclonal antibodies (MoAbs) directed against SCLC antigens; growth factors including GRP and IGF. GRP or human bombesin produced by the tumor cells favours their own growths; in cytogenetics, with the observation of a characteristic chromosomal abnormality: the deletion of the short arm of chromosome 3 (3p 14-23). The region deleted is currently under study to identify the genes potentially involved in the oncogenesis of SCLC. the activation of several oncogenes: C-myc, N-myc, L-myc, Myb, Raf-1. The amplification of C-myc favors the tumor cell progression and is related to a bad prognosis. This biological approach has confirmed the neuroendocrine origin of these tumor cells (as a result of protein studies of the cytoskeleton and of MoAbs); it has allowed the use of tumor markers in the diagnosis and work-up of SCLC and the consideration of new therapeutic approaches. Current studies concern the deletion of 3p- and the integration of the cytogenetic data, growth factors and oncogenes in a coherent model of the genesis of SCLC.

Biomarkers, Tumor↗
PubMed1975

Antigenic variation of neuraminidase of human type A influenza (H3N2) viruses isolated in Berlin (West).

After the emergence of the A/Hong Kong/1/68 (H3N2) strain of influenza virus antigenic variation of the hemagglutinin and neuraminidase antigens have been demonstrated leading to the identification of the variants A/England/42/72,a/Port Chalmers/1/73 and A/Scotland/840/74. This study describes antigenic changes of neuraminidases in influenza viruses isolated since 1968 in Berlin (West). A collection of 13 isolates of human type A influenza was studied in neuraminidase inhibition tests. The results are in line with data from other laboratories indicating a major change in the neuraminidase antigen as early as December 1969. The strains isolated at that time cross-reacted with an antiserum against the N2-Hong Kong enzyme to less than 50%. During the following years (1970 to 1972) the neuraminidase remained fairly stable. Serological cross-reactions showing 47 to 38% inhibition as compared to the homologous N2-antigen. The neuraminidase of the A/Berlin/3/72 strain revealed a close antigenic relationship to the later appearing A/Port Chalmers 1/73 variant. Two strains isolated in 1975 (January) showed an even further drift away from the then representative A/Port Chalmers/1/73 strain. The fact that the neuraminidase antigens of the Berlin viruses had changed in December 1969 may account for the severe 1969/70 influenza epidemic in Berlin affecting a large proportion of the population. Prevalent anti-neuraminidase antibodies may play a role in restricting a variant carrying a new hemagglutinin to primarily infected individuals by cross-reacting with a closely related enzyme.

Antigens, Viral↗
PubMed1984

The occurrence of the alpha G-Philadelphia-globin allele on a double-locus chromosome.

Hb G-Philadelphia, an alpha-globin allele, is expressed as either 20%, 30%, or 40% of the total hemoglobin. Restriction analyses published thus far have shown that among persons with 30% and 40% hemoglobin (Hb) G the alpha G allele is seen only in a single-locus haplotype. We now report the identification of a second haplotype in which the alpha G allele is found in tandem with an alpha A allele. This haplotype has been found present in DNA from the members of one family in which Hb G is expressed as 20% of the total hemoglobin, determined by both cellulose acetate electrophoresis and high-performance liquid chromatography (HPLC). Synthesis was balanced in all individuals. The identification of a variant alpha-globin allele in two distinct haplotypes presents the possibility of independent mutation. However, an alternative explanation cannot be ruled out; namely, that the original allele may have become distributed among the two haplotypes by unequal crossing-over.

Alleles↗
PubMed1982

Lymphocyte proteins in Huntington's disease: quantitative analysis by use of two-dimensional electrophoresis and computerized densitometry.

We used quantitative two-dimensional electrophoresis to study lymphocyte proteins in Hungtington's disease. Three hundred and six polypeptides from 14C-labeled, phytohemagglutinin-stimulated lymphocytes were measured for variation in relative spot density and 186 for variation in spot position by use of a computer program requiring operator interaction. Each polypeptide was measured in a total of 30 electrophoretograms from 28 individuals, including 13 with Huntington's disease, 2 at risk for it, and 13 controls. The study included two sets of identical twins and, as neurological controls, individuals with neurofibromatosis, Alzheimer's disease, or Shy-Drager syndrome. Seven protein polymorphisms were identified among the 186 most dense polypeptides of each gel, corresponding to a minimum average heterozygosity of 1.4%. Stringent criteria were used to define polymorphic proteins, including observation of at least one individual with each of two homozygous phenotypes and one with the heterozygous phenotype, demonstration of the expected gene dosage relationship by quantitative densitometry, consistency with genetic relationships, and reproducibility. One polymorphic protein showed three electrophoretically variant alleles. Our identification of seven polymorphisms among the 186 proteins measured on a single electrophoretogram illustrates the potential of this technique for performing linkage analysis in diseases of genetic origin. However, we observed no quantitative or positional protein variations that were characteristic of (i.e. specific for) Huntington's disease.

Blood Proteins↗