Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “common variation”

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
PubMed2000

Sequence variation within the neuropeptide Y gene and obesity in Mexican Americans.

OBJECTIVE: Recently, we reported evidence for linkage between neuropeptide Y (NPY) and both obesity and several obesity-related quantitative measures in a sample of Mexican Americans from Starr County, Texas. The purpose of this study was to investigate putative variation within the coding and promoter regions of NPY. RESEARCH METHODS AND PROCEDURES: Five young, obese individuals (body mass index [BMI] 33 to 45 kg/m2, age 14 to 30 years); five adult, lean individuals (BMI 20 to 26 kg/m2, age 39 to 65 years); and five sibling pairs sharing no alleles that were identical by descent at a marker locus proximal to NPY were selected for fluorescence-based sequencing of approximately 1100 base pairs (bp) immediately 5' from the start site and all four exons of NPY. We identified a total of eight variant sites, including a 2-bp insertion/deletion (I/D) within a putative negative regulatory region (-880I/D) and a 17-bp deletion at the exon 1/intron 1 junction (69I/D). The -880I/D and 69I/D variants were typed in a separate random sample of Mexican Americans (N = 914) from Starr County, Texas. RESULTS: Analyses of variance resulted in a significant association between -880I/D and waist-to-hip ratio (p = 0.041) in the entire sample and between -880I/D and BMI (p = 0.031), abdominal circumference (p = 0.044), and waist-to-hip ratio (p = 0.041) in a non-obese subsample (BMI < 30 kg/m2, n = 594). The 69I/D variant was observed in only one pedigree and does not appear to segregate with obesity within this pedigree. DISCUSSION: This study reports newly identified common human sequence variation within the regulatory and coding sequence of NPY. Several variants were observed, and of those tested, the -880I/D promoter region variant may influence body fat patterning in non-obese individuals but does not appear to play a major role in the etiology of common forms of obesity in this population.

Adolescent↗
PubMed1992

A study of phenotypic variation of Staphylococcus epidermidis using Congo red agar.

This study examines a series of phenotypic variants of Staphylococcus epidermidis that were generated from a pair of parent variants, isolated from valvular tissue of a patient with prosthetic valve endocarditis. The variants were initially classified by examining their colonial morphology on Congo red agar. In addition to differences in Congo red binding and colonial morphology, they differed in the expression of several surface components and enzymes. Despite these phenotypic differences, all variants had the same restriction endonuclease profile of plasmid DNA. Examination of a collection of clinical isolates demonstrated that phenotypic variation is a common property of S. epidermidis. The ability to express different combinations of surface components and enzymes could contribute to the virulence of S. epidermidis strains by enabling these organisms to colonize a range of diverse environments.

Agar↗
PubMed1984

Further evidence for a significant effect of fetal genes on variation in birth weight.

The contribution of fetal and maternal genes to the variation in birth weight was estimated in a sample of 5,625 grandchildren of monozygotic and dizygotic twins. Fetal and maternal genetic effects were separated by comparing the covariance structure for offspring of daughters of twins with that for offspring of sons of twins. Only insignificant amounts (3.0%) of the total variance in birth weight could be accounted for by maternal genes, while fetal genes seemed to account for the major part (69.4%) of the variation. Environmental factors common to sibs could explain 8.6% and random environmental factors 19.0% of the total variance. The findings are consistent with the results of an earlier study of birth weight in the same population but differ from findings in other populations.

Analysis of Variance↗
PubMed2003

Infection of a ventriculoatrial shunt with phenotypically variable Staphylococcus epidermidis masquerading as polymicrobial bacteremia due to various coagulase-negative Staphylococci and Kocuria varians.

The diagnosis of bloodstream infection with coagulase-negative staphylococci is frequently based on the isolation of the same organism from more than one blood culture. Phenotypic variation is a common characteristic of pathogenic strains of Staphylococcus epidermidis which may affect species identification by the microbiology laboratory. We describe a patient with a new onset of nephritis and gram-positive bacteremia. Gram-positive cocci grew in multiple blood cultures and were identified by the Vitek 2 system as Kocuria varians, Staphylococcus hyicus, and S. epidermidis. Bacterial isolates grew on blood agar and Congo red agar plates as two distinct morphotypes and exhibited phenotypic variation. Neither morphotype could be identified by the API-Staph assay. Cellular fatty acid analysis identified one of the morphotypes as S. epidermidis but could not identify the other morphotype. All isolates were found to be identical by pulsed-field gel electrophoresis, and both colonial morphotypes were identified as S. epidermidis by 16S ribosomal gene sequencing. Phenotypic variation of S. epidermidis may affect identification to the species level by phenotype-based identification systems. Caution should be exercised when differentiating between true infection and contamination based on strain identification.

Actinomycetales↗
PubMed2001

[Introduction to Go! Poly, a human genome polymorphism database].

Databases play an important role in the study of genetic polymorphism. To meet the need for more studies of human genome polymorphism by Chinese medical and pharmaceutical community, a gene oriented human genome polymorphism database-Go! Poly was constructed. As a generalized polymorphism database, Go! Poly extracted human gene-linked sequence variations of all common types from various public resources including scientific journals and Web resources such as HGBASE (http://hgbase.cgr.ki.se) and dbSNP (http://www.ncbi.nlm.nih.gov/SNP/). The polymorphism data were then categorized into different gene loci, and the reference sequences given by LocusLink were used as positioning reference. To facilitate the use, a friendly web interface and a text based query strategy were implemented. Users can fetch specific polymorphism data in just three steps: find specific gene locus by simple search, display sequence variation information of a specific gene locus select, and view the final result of a specific variation site. Besides, a web-based submission tool is provided for direct submission, which can make the polymorphism information generated by the Chinese scientific community available from this resource.

China↗
PubMed2002

Analysis of length variation in the V1-V2 region of env in nonsubtype B HIV type 1 from Uganda.

We optimized an assay for analysis of length variation in the V1-V2 region of HIV-1 env in plasma samples from Uganda. V1-V2 env length variation was analyzed in 31 plasma samples containing subtype A, C, D, or A/D recombinant HIV-1. DNA corresponding to the V1-V2 region was amplified by nested PCR. One of the primers in the second step of the PCR was fluorescently labeled. Successful amplification was confirmed by agarose gel electrophoresis. V1-V2 length variation of PCR products was analyzed with an ABI PRISM 3100 genetic analyzer and GeneScan software. A diversity score was generated for each sample on the basis of the degree of fragment length variation. The V1-V2 region was successfully amplified from 30 of 31 samples. Fragment length analysis was successful for all of those 30 samples. The diversity score and lengths of V1-V2 fragments were unique for each sample. This assay can be used for analysis of V1-V2 length variation in subtypes commonly found in Uganda. This assay may be helpful for studies examining the impact of env length diversity on HIV-1 transmission and pathogenesis in regions where these subtypes are prevalent.

Female↗
PubMed2000

Frequency of consumption and nutrient composition of composite dishes commonly consumed in the UK by South Asian Muslims originating from Bangladesh, Pakistan and East Africa (Ismailis).

INTRODUCTION: This paper presents information on the nutrient composition of commonly consumed traditional dishes eaten by the three major South Asian Muslim groups residing in Britain, namely Bangladeshi, Pakistani and East African Ismaili Muslims. METHODS: Information regarding the most common dishes consumed by South Asian Muslims originating from Bangladesh, Pakistan and East Africa (Ismailis) and living in London was obtained from 7-day menu records over two seasons. For each common dish, weighed recipes were collected in triplicate and the composition (energy and selected nutrients) was calculated from the ingredients and cooked weight of the dish. RESULTS: The three Muslim groups showed considerable variation in traditional foods commonly consumed as well as variation in fat and energy contents of similar recipes both within and between groups. Nutrient composition of commonly consumed dishes is presented calculated from the recipe nearest the average in terms of fat and energy for a particular dish. DISCUSSION AND CONCLUSIONS: The potential uses of the data, one of which would be to improve dietary compliance (especially to lower fat intakes) amongst the three diverse South Asian Muslim groups, are discussed.

Journal Article↗
PubMed2006

Identification of atherosclerosis-modifying genes: pathogenic insights and therapeutic potential.

Atherosclerosis is a common, complex trait, with genetic variation in many genes and the environment contributing to risk for this condition, which has multiple and highly variable phenotypic manifestations. Progress has been made in the identification of atherosclerosis-modifying genes in both human studies and through the use of animal models. In the future, it may be possible to administer a genetic test for variation in a handful of the most common atherosclerosis-modifier genes, and thus predict if a patient is likely to develop atherosclerosis and ischemic heart disease. These patients could then be treated aggressively to lower their low-density lipoprotein cholesterol levels and other risk factors, including counseling to make adjustments in their lifestyle. This review will summarize the methods and results thus far in the identification of atherosclerosis-modifier genes.

Animals↗
PubMed2004

Sequence variations of the alpha-globin genes: scanning of high CG content genes with DHPLC and DG-DGGE.

The alpha-globin chains are encoded by two duplicated genes (HBA2 and HBA1, 5'-3') showing overall sequence homology >96% and average CG content >60%. alpha-Thalassemia, the most prevalent worldwide autosomal recessive disorder, is a hereditary anemia caused by sequence variations of these genes in about 25% of carriers. We evaluated the overall sensitivity and suitability of DHPLC and DG-DGGE in scanning both the alpha-globin genes by carrying out a retrospective analysis of 19 variant alleles in 29 genotypes. The HBA2 alleles c.1A>G, c.79G>A, and c.281T>G, and the HBA1 allele c.475C>A were new. Three pathogenic sequence variations were associated in cis with nonpathogenic variations in all families studied; they were the HBA2 variation c.2T>C associated with c.-24C>G, and the HBA2 variations c.391G>C and c.427T>C, both associated with c.565G>A. We set up original experimental conditions for DHPLC and DG-DGGE and analyzed 10 normal subjects, 46 heterozygotes, seven homozygotes, seven compound heterozygotes, and six compound heterozygotes for a hybrid gene. Both the methodologies gave reproducible results and no false-positive was detected. DHPLC showed 100% sensitivity and DG-DGGE nearly 90%. About 100% of the sequence from the cap site to the polyA addition site could be scanned by DHPLC, about 87% by DG-DGGE. It is noteworthy that the three most common pathogenic sequence variations (HBA2 alleles c.2T>C, c.95+2_95+6del, and c.523A>G) were unambiguously detected by both the methodologies. Genotype diagnosis must be confirmed with PCR sequencing of single amplicons or with an allele-specific method. This study can be helpful for scanning genes with high CG content and offers a model suitable for duplicated genes with high homology.

Alleles↗
PubMed1975

Incidence of chromosome aberrations among 11148 newborn children.

Chromosome analysis has been made of 11148 children; 29 had sex chromosome abnormalities (2.60 per 1000) and 64 autosomal abnormalities (5.74 per 1000). The total incidence of major chromosome abnormalities was 8.34 per 1000. The incidence of chromosome variations was 16.8 per 1000. The most common variants were those with variation in size of short arms-satellites in D and G chromosomes and variations in Y chromosome size. So far, very little is known about the significance of such chromosome variations. The incidence of most chromosome abnormalities in liveborn children is well established by now from studies of a total of 54749 consecutively liveborn children in 6 studies as shown in Table 1. More chromosome studies of liveborn children are, however, needed for several purposes such as finding families with chromosome translocations, studying segregation rates and giving genetic advice to families with inheritable chromosome aberrations and an increased risk of getting children with unbalanced chromosome abnormalities, mental retardation and physical abnormalities. One of the main purposes in chromosome examination of newborn children is to study the development of children with different chromosome abnormalities, especially those with sex chromosome abnormalities, and compare then with controls, treat them when needed and give advice to the parents of such children.

Chromosome Aberrations↗
PubMed1994

Quality control of extemporaneously prepared microdose captopril capsules: weight variation versus content uniformity.

Microdose (1 mg) captopril therapy is commonly used for the initial dose titration in patients with congestive heart failure. Since this dosage form is not commercially available, it has to be extemporaneously compounded. Quality control of each batch is commonly evaluated using the weight variation technique described in the USP. Despite careful titration with microdose, captopril capsules variability in patient's response has been observed. In order to explain this fluctuation, the actual content of extemporaneously compounded microdose captopril capsules was evaluated using a high pressure liquid chromatographic assay. Microdose captopril capsules were prepared by triturating 25 mg tablets with lactose in a mortar using standard geometric dilution technique and a Sharpe-Dohme hand-operated capsule filling machine. Forty-eight microdose captopril capsules were randomly selected from the compounded batch and were individually assayed for captopril amount. The mean +/- standard deviation (SD) amount of captopril in each capsule was 1.27 g +/- 0.31 mg with a range of 0.84 g to 1.96 mg. The coefficient of variation was 24.5%. Ten captopril capsules were randomly selected from the compounded batch and were individually weighed. The capsules had a mean weight +/- SD of 198.3 g +/- 21.2 mg and a coefficient of variation of 7.3%. Even though the extemporaneously prepared microdose captopril capsules were within acceptable limits for weight variation described in the USP, the actual dose administered to the patients could vary by as much as 24.5%.

Capsules↗
PubMed2002

Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection.

OBJECTIVES: Needle liver biopsy has been shown to have a high rate of sampling error in patients with diffuse parenchymal liver diseases. In these cases, the sample of liver tissue does not reflect the true degree of inflammation, fibrosis, or cirrhosis, despite an adequate sample size. The aim of this study was to determine the rate and extent of sampling error in patients with chronic hepatitis C virus infection, and to assess the intraobserver variation with the commonly used scoring system proposed by Scheuer and modified by Batts and Ludwig. METHODS: A total of 124 patients with chronic hepatitis C virus infection underwent simultaneous laparoscopy-guided biopsies of the right and left hepatic lobes. Formalin-fixed paraffin-embedded sections were stained with hematoxylin and eosin and with trichrome. The slides were blindly coded and randomly divided among two hepatopathologists. Inflammation and fibrosis were scored according to the standard grading (inflammation) and staging (fibrosis) method based on the modified Scheuer system. Following the interpretation, the slides were uncoded to compare the results of the right and left lobes. Fifty of the samples were blindly resubmitted to each of the pathologists to determine the intraobserver variation. RESULTS: Thirty of 124 patients (24.2%) had a difference of at least one grade, and 41 of 124 patients (33.1%) had a difference of at least one stage between the right and left lobes. In 18 patients (14.5%), interpretation of cirrhosis was given in one lobe, whereas stage 3 fibrosis was given in the other. A difference of two stages or two grades was found in only three (2.4%) and two (1.6%) patients, respectively. Of the 50 samples that were examined twice, the grading by each pathologist on the second examination differed from the first examination in 0% and 4%, and the staging differed in 6% and 10%, respectively. All observed variations were of one grade or one stage. CONCLUSIONS: Liver biopsy samples taken from the right and left hepatic lobes differed in histological grading and staging in a large proportion of chronic hepatitis C virus patients; however, differences of more than one stage or grade were uncommon. A sampling error may have led to underdiagnosis of cirrhosis in 14.5% of the patients. These differences could not be attributed to intraobserver variation, which appeared to be low.

Adult↗
PubMed2006

A pharmacokinetic formalism explicitly integrating the patient drug compliance.

The adherence phenomenon is now well recognized to seriously compromise drug efficacy. In this paper, we analyze the role of compliance through drug intake history as an integral part of the pharmacokinetic process. Being concerned with what is accessible in medical practice, we develop a stochastic approach to model the drug intake behavior that we combine with a conventional pharmacokinetic model in order to investigate the effect of drug intake history on the pharmacokinetic time-course. For this purpose, we explicitly formalize the plasma concentration variations for the most common administration routes. This analytical approach allows to characterize drug concentration variations directly inherited from patient compliance.

Animals↗
PubMed2006

Novel variants in the hotspot region of RP1 in South African patients with retinitis pigmentosa.

PURPOSE: Mutations in the hotspot of RP1 are reportedly responsible for 4-7% of autosomal dominant retinitis pigmentosa (ADRP) in the United States, Canada, and Europe. South Africa (SA) has unique subpopulations and a comparatively low observed frequency of rhodopsin mutations, which lead to this investigation of the contribution of RP1 mutations to the ADRP disease burden in SA. METHODS: Fifty-seven affected, unrelated South African individuals with ADRP were selected for mutation screening of the RP1 hotspot, using denaturing high performance liquid chromatography (HPLC). Variants were identified by direct sequencing, after which cosegregation analysis and population frequency studies were performed using restriction fragment length polymorphism analysis, nondenaturing HPLC, or denaturing HPLC. RESULTS: Three mutations were identified, including two novel sequence variations and the common Arg677X mutation. A wide spectrum of disease severity was observed in the families with these RP1 gene mutations. Two nondisease-associated polymorphisms were also detected, with the frequency of one of these variants being significantly low in Black African individuals. CONCLUSIONS: Mutations were only found in Caucasian families with origins in the British Isles. The observed RP1 mutation frequency of 5.3% in SA ADRP patients is comparable to the frequency reported in other populations.

Eye Proteins↗
PubMed2004

Genotypic variation and stability of four variable-number tandem repeats and their suitability for discriminating strains of Mycobacterium leprae.

It has not been possible to distinguish different strains of Mycobacterium leprae according to their genetic sequence. However, the genome contains several variable-number tandem repeats (VNTR), which have been used effectively in strain typing of other bacteria. To determine their suitability for differentiating M. leprae, we developed PCR systems to amplify 5 different VNTR loci and examined a battery of 12 M. leprae strains derived from patients in different regions of the United States, Brazil, Mexico, and the Philippines, as well as from wild armadillos and a sooty mangabey monkey. We found diversity at four VNTR (D = 0.74), but one system (C(16)G(8)) failed to yield reproducible results. Alleles for the GAA VNTR varied in length from 10 to 16 copies, those for AT(17) varied in length from 10 to 15 copies, those for GTA varied in length from 9 to 12 copies, and those for TA(18) varied in length from 13 to 20 copies. Relatively little variation was seen with interspecies transfer of bacilli or during short-term passage of strains in nude mice or armadillos. The TA(18) locus was more polymorphic than other VNTR, and genotypic variation was more common after long-term expansion in armadillos. Most strain genotypes remained fairly stable in passage, but strain Thai-53 showed remarkable variability. Statistical cluster analysis segregated strains and passage samples appropriately but did not reveal any particular genotype associable with different regions or hosts of origin. VNTR polymorphisms can be used effectively to discriminate M. leprae strains. Inclusion of additional loci and other elements will likely lead to a robust typing system that can be used in community-based epidemiological studies and select clinical applications.

Genetic Variation↗
PubMed1982

Variation in mouse major urinary protein (MUP) genes and the MUP gene products within and between inbred lines.

The mouse major urinary proteins (MUPs) and the unprocessed in vitro translation products of MUP mRNA were each resolved by isoelectric focusing (IEF). The urinary MUPs showed about 15 distinct components, and the unprocessed MUPs about 20. In each case wide variation was observed in the relative intensities of individual bands. A comparison of three inbred lines (C57BL, BALB/c and JU) showed inter-line variation in the patterns both of the urinary MUPs and of the unprocessed MUPs. A series of experiments was carried out with a cloned MUP cDNA probe. All three inbred lines contain the same number (about 20) of MUP genes per haploid genome. In Southern blot analysis of genomic DNA the MUP genes displayed complex patterns which we interpret as showing variation on a common basic MUP gene sequence. For each combination of restriction enzymes tested, one size of fragment carried more than half of the total label, and this fragment was always the same in the three inbred lines. Inter-line differences were observed in the patterns of some of the less reactive fragments. MUP mRNA consists of at least two distinct species with sizes of 1 and 1.2 kb, which reacted with the probe in a label ratio of about 0.5 to 1. In the three inbred lines this ratio was essentially the same.

Animals↗
PubMed1986

Beta-glucosidase: substrate, solvent, and viscosity variation as probes of the rate-limiting steps.

The second-order rate constants (kcat/Km) for the beta-glucosidase-catalyzed hydrolysis of aryl beta-D-glucopyranosides show a bell-shaped dependence of pH. The pKas that characterize this dependence are 4.4 (delta Hion approximately equal to 0) and 6.7 (delta Hion approximately equal to 0). In D2O these pKas are increased by 0.5 (+/- 0.1) unit, but there is no solvent isotope effect on the pH-independent second-order rate constant. Nath and Rydon [Nath, R. L., & Rydon, H. N. (1954) Biochem. J. 57, 1-10] examined the kinetics of the beta-glucosidase-catalyzed hydrolysis of a series of substituted phenyl glucosides. We have extended this study to include glucosides with phenol leaving groups of pKa less than 7. Brønsted plots for this extended series were nonlinear for both kcat/Km and kcat. Brønsted coefficients for those compounds with leaving groups of pKa greater than 7 (for kcat/Km) or pKa greater than 8.5 (for kcat) were nearly equal to -1.0, indicating substantial negative charge buildup on the leaving group in the transition state. The nonlinearity indicates an intermediate in the reaction. This was confirmed by partitioning experiments in the presence of methanol as a competing glucose acceptor. A constant product ratio, [methyl glucoside]/[glucose], was found with aryl glucoside substrates varying over 16,000-fold in reactivity (V/K), indicative of a common intermediate. Viscosity variation (in sucrose-containing buffers) was used to probe the extent to which the beta-glucosidase reactions are diffusion-controlled.(ABSTRACT TRUNCATED AT 250 WORDS)

Deuterium↗
PubMed2006

Role of common human TRIM5alpha variants in HIV-1 disease progression.

BACKGROUND: The retroviral restriction factor tripartite motif protein (TRIM)5alpha, is characterized by marked amino acid diversity among primates, including specific clusters of residues under positive selection. The identification of multiple non-synonymous changes in humans suggests that TRIM5alpha variants might be relevant to retroviral pathogenesis. Previous studies have shown that such variants are unlikely to modify susceptibility to HIV-1 infection, or the course of early infection. However, the longterm effect of carrying Trim5alpha variants on disease progression in individuals infected with HIV-1 has not previously been investigated. METHODS: In a cohort of 979 untreated individuals infected with HIV-1 with median follow up 3.2 years and 9,828 CD4 T cell measurements, we analysed common amino acid variations: H43Y, V112F, R136Q, G249D, and H419Y. The rate of CD4 T cell decline before treatment was used as the phenotype. In addition, we extended previous work on the in vitro susceptibility of purified donor CD4 T cells (n = 125) to HIV-1 infection, and on the susceptibility of HeLa cells that were stably transduced with the different TRIM5 variants. Haplotypes were analysed according to the most parsimonious evolutionary structure, where two main human TRIM5alpha groups can be defined according to the residue at amino acid 136. Humans present both Q136 and R136 at similar frequency, and additional TRIM5alpha amino acid variants are almost exclusively derived from R136-carrying haplotypes. RESULTS: We observed modest differences in disease progression for evolutionary branches carrying R136-derived haplotypes, and with the non-synonymous polymorphisms G249D and H419Y. In vitro analysis of susceptibility of donor CD4 T cells, and of the various transduced HeLa cell lines supported the absence of significant differential restriction of HIV-1 infection by the various huTRIM5alpha alleles. CONCLUSION: Common human variants of TRIM5alpha have no effect or modest effect on HIV-1 disease progression. These variants occur at sites conserved throughout evolution, and are remote from clusters of positive selection in the primate lineage. The evolutionary value of the substitutions remains unclear.

Adult↗