Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “programmed genetic 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 1,027 records · Page 57Linked to original sources
PubMed1995

Exploratory analysis of population genetic assessment as a water quality indicator. II. Campostoma anomalum.

Biological monitoring programs to assess contaminant-induced impacts in aquatic systems are being developed and implemented by several federal agencies and many states. Genetic diversity and allozyme frequency may be valuable indicators of such impact because they are both sensitive to exposure and ecologically relevant in populations. The purpose of this study was to examine whether genetic diversity and structure of Campostoma anomalum populations could serve as effective biomarkers of exposure to anthropogenic stress by comparing genetic measures with other biological indicators of water quality. Fish were collected from 14 sites on seven streams by the Ohio Environmental Protection Agency as part of their stream water quality evaluation program. Values for the Index of Biological Integrity (IBI) and the Invertebrate Community Index (ICI) were determined for these 14 sites. Starch gel electrophoresis was used to collect genetic data for eight variable enzyme loci. Genetic diversity measures were not associated with site IBI or ICI values. However, the range of site IBI and ICI values was limited. Allele and genotype frequencies were significantly different at the point source compared to sites upstream and downstream indicating that genetic structure may be an indicator of water quality that is sensitive enough to detect change prior to species loss.

Acid Phosphatase↗
PubMed2005

Therapeutic drug monitoring and the inhibitory quotient of antiretroviral drugs: can they be applied to the current situation?

Therapeutic drug monitoring is attracting growing interest as a means of increasing the effectiveness of antiretroviral therapy and of decreasing its toxicity, although data supporting this strategy are still scarce. Currently, nucleoside analog reverse-transcriptase inhibitors (NARTI) are not candidates because their effect depends on their active intracellular form and not on plasma concentration. Protease inhibitors (PI) and non-nucleoside analogue reverse-transcriptase inhibitors (NNARTI) meet the criteria for therapeutic drug monitoring. The main limitations are that the parameters to be monitored in order to measure exposure to the drug and the effective concentration of the drug have not been well defined. The few studies performed in treatment-naive patients have demonstrated that monitoring improves therapeutic efficacy. This strategy will be particularly useful when the risk of subtherapeutic or toxic concentrations is especially high (pharmacokinetic interactions, intestinal malabsorption, adverse effects, virological failure without obvious cause, pregnancy, children). Although it remains to be standardized, the inhibitory quotient integrates pharmacological and virological parameters and is useful in patients with prior virological failure. Any therapeutic drug monitoring program should be accompanied by measures to monitor and improve treatment adherence. There are good reasons to believe that therapeutic drug monitoring can be useful to improve treatment in specific circumstances. However, before its widespread use as a routine method can be recommended, the parameters to be used should be standardized and studies with appropriate methodology should be performed to define the role of therapeutic drug monitoring in distinct clinical situations.

Algorithms↗
PubMed1972

Some examples of the use of computer-produced contour plots in the fitting of enzyme rate equations to reaction-velocity measurements.

The use of computer-based isotach plots, relating reaction velocity to simultaneous variation of two substrates or effectors of an enzyme, in producing estimates of the parameters of enzyme rate equations was investigated. The computer program (;SYMAP') incorporates an interpolation algorithm, and the superiority of this over visual estimation in producing interpolated velocity values for the estimation of parameter values by conventional double-reciprocal plots is described. The usefulness of the SYMAP program in monitoring the process of fitting data obtained by simultaneous changes in two experimental variables is also described. It is shown that if the residual errors are weighted by a procedure described elsewhere (Ottaway, 1971b, 1973), the percentage error of the computed velocity is distributed evenly over a plot which contains a 100-fold variation in the concentration of one substrate and a 500-fold variation in the concentration of Mg(2+), and in which the velocity of the reaction (that catalysed by NAD kinase) varies over a 60-fold range. The two-dimensional percentage error plot was used to assess the limits within which an incomplete inhibition equation is valid, and to detect a discrepancy in an expected good fit, caused by an impurity in one of the substrates.

Adenosine Triphosphate↗
PubMed2001

Naturally occurring circular permutations in proteins.

A pair of proteins is defined to be related by a circular permutation if the N-terminal region of one protein has significant sequence similarity to the C-terminal of the other and vice versa. To detect pairs of proteins that might be related by circular permutation, we implemented a procedure based on a combination of a fast screening algorithm that we had designed and manual verification of candidate pairs. The screening algorithm is a variation of a dynamic programming string matching algorithm, in which one of the sequences is doubled. This algorithm, although not guaranteed to identify all cases of circular permutation, is a good first indicator of protein pairs related by permutation events. The candidate pairs were further validated first by application of an exhaustive string matching algorithm and then by manual inspection using the dotplot visual tool. Screening the whole Swissprot database, a total of 25 independent protein pairs were identified. These cases are presented here, divided into three categories depending on the level of functional similarity of the related proteins. To validate our approach and to confirm further the small number of circularly permuted protein pairs, a systematic search for cases of circular permutation was carried out in the Pfam database of protein domains. Even with this more inclusive definition of a circular permutation, only seven additional candidates were found. None of these fitted our original definition of circular permutations. The small number of cases of circular permutation suggests that there is no mechanism of local genetic manipulation that can induce circular permutations; most examples observed seem to result from fusion of functional units.

Algorithms↗
PubMed2000

Sequence, expression and functional analysis of the Coccidioides immitis ODC (ornithine decarboxylase) gene.

The ornithine decarboxylase (ODC) gene of the human respiratory fungal pathogen, Coccidioides immitis (Ci) was cloned, sequenced, chromosome-mapped, and expressed in Escherichia coli (Ec). The genomic, cDNA and translated sequences are presented. Transformation of an ODC null mutant strain of Ec (EWH 319) with the Ci ODC gene was conducted to confirm function of the protein encoded by the fungal gene. Activity of the enzyme by the bacterial transformant was inhibited by 1, 4-diamino-2-butanone (DAB), a known inhibitor of eukaryotic ODC. Temporal expression of the Ci ODC gene during the parasitic cell cycle is constitutive, based on results of RT PCR. However, results of enzyme activity assays of cell homogenates obtained at different stages of parasitic cell development in vitro showed that the functional protein is present only during periods of isotropic growth and segmentation, and these morphogenetic events can be arrested by the addition of DAB. The observed absence of a difference in steady-state mRNA transcript amounts, and the developmentally correlated variation in levels of enzyme activity, suggest a translational or post-translational mechanism of ODC regulation. Since no PEST sequence was detected in the Ci ODC, enzyme regulation by programmed protein degradation as reported for many other eukaryotic ODCs may not occur in this case. ODC activity appears to play a key role in the morphogenesis of Ci, and the enzyme could be a rational target for therapy of disseminated coccidioidomycosis.

Amino Acid Sequence↗
PubMedDate not supplied

[Genomic study of the hereditary pathology and genetic diversity of the Siberian population].

The review considers the results of genome research on the Russian program Human Genome carried out in the Institute of Medical Genetics (Tomsk) from 1990. The three major fields were molecular cytogenetics and chromosomal disorders, genomics of Mendelian and high-incidence diseases, and ethnogenomics of the North Asian population. Several human genes were cytogenetically mapped, and numerical and structural abnormalities associated with human diseases studied by fluorescence hybridization. Procedures of DNA diagnostics were developed for 15 hereditary diseases. New data were obtained on genetic heterogeneity of idiopathic hypertrophic cardiomyopathy. The genetic bases of multifactorial (atopic bronchial asthma) and infectious (tuberculosis) diseases were analyzed. The North Eurasian population (41 local populations of 21 ethnic groups) was tested for genetic diversity with numerous genetic markers, including Y-chromosomal haplotypes, autosomal microsatellites, and polymorphic Alu insertions.

Ethnicity↗
PubMed2005

Relationship between a high-risk haplotype in the DTNBP1 (dysbindin) gene and clinical features of schizophrenia.

OBJECTIVE: The purpose of this study was to determine whether a haplotype in the dystrobrevin binding protein 1 (DTNBP1) gene previously associated with schizophrenia not only increases the susceptibility to psychotic illness but also to a more or less clinically specific form of psychotic illness. METHOD: In the Irish Study of High-Density Schizophrenia Families, subjects with psychotic illness (N=755) were given lifetime ratings of clinical features according to the Operational Criteria Checklist for Psychotic Illness. Exploratory and confirmatory factor analyses were used to extract five factors-hallucinations, delusions, negative, manic, and depressive symptoms-and to create factor-derived scores. The family-based transmission disequilibrium test operationalized in the program TRANSMIT was used to determine whether a high-risk haplotype in the DTNBP1 gene was overtransmitted to subjects in the upper 20th and 40th percentiles for each factor score. These results were compared to baseline overtransmission by examining the empirical distribution of chi-square statistics in groups of 5,000 replicates in which 20% and 40% of ill subjects were randomly selected. This analysis was done for both narrow and broad definitions of psychotic illness. RESULTS: Subjects in the upper 40th percentile for the negative symptom factor--in both the narrowly (p=0.004) and broadly (p=0.01) defined illness groups--were more likely to inherit the high-risk haplotype than would be expected by chance. No other significant relationships between clinical features and high-risk haplotype transmission were observed. CONCLUSIONS: The etiologically relevant variation in DTNBP1, which is in presumptive linkage disequilibrium with the high-risk haplotype, may predispose individuals to a form of psychotic illness associated with high levels of negative symptoms. This finding supports previous evidence suggesting that genetic factors influence the clinical heterogeneity of schizophrenia.

Carrier Proteins↗
PubMed1996

Allelic variation of the polyubiquitin gene in the tobacco hawkmoth, Manduca sexta, and its regulation by heat shock and programmed cell death.

The intersegmental muscles (ISMs) of the tobacco hawkmoth, Manduca sexta, undergo programmed cell death (PCD) following adult eclosion in response to a decline in the circulating titer of the hormone 20-hydroxyecdysone. The ability of the ISMs to die requires de novo gene expression and a number of cDNAs representing differentially expressed genes have been isolated from condemned cells. One of the genes that is dramatically up-regulated with ISM death is polyubiquitin, which has been shown in many organisms to function as a heat shock protein and as an essential mediator of proteolysis. Northern blot analysis of ISM RNA samples pooled from multiple individuals demonstrated the presence of several polyubiquitin transcripts. In this study, we sought to determine: 1) if these transcripts were the product of multiple genes or multiple alleles, and 2) if all polyubiquitin genes/alleles in the moth are regulated by both heat shock and the endocrine signals that regulate death. Data from Southern blot analysis suggested that the Manduca genome has a single polyubiquitin gene that is represented by multiple alleles. Transcript analysis supported the hypothesis that all polyubiquitin alleles are regulated by both heat shock and the hormonal cues that regulate muscle death. Polyubiquitin transcripts accumulated to much higher levels and had longer half-lives following hormonal induction relative to that seen in response to heat shock. These data suggest that there are multiple polyubiquitin alleles in the laboratory population of Manduca, all of which share common regulatory sequences that drive expression to meet the needs for proteolysis involved in both heat stress and death.

Alleles↗
PubMed1996

Envelope gene sequences of human T-lymphotropic virus type 1 in Taiwan.

Three major types of HTLV-1 had been proposed, the Melanesian type, the Zairian type, and the cosmopolitan type, which was further divided into subtypes A, B and C, according to the phylogenetic tree constructed from LTR sequences of current HTLV-isolates. In this study, the envelope gene sequences of HTLV-1 from 9 Taiwanese were analyzed. Based on the phylogenetic tree constructed by unweighted pair group method and the sequence homology analysis by GCG computer programs, the envelope gene sequences of HTLV-1 proviruses from these 9 Taiwanese belonged to subtype A or subtype B of the cosmopolitan type and were closely related to HTLV-1 from Japan. Twelve subtype-specific nucleotide variations were deduced from the comparison of complete or partial envelope gene sequences of 16 HTLV-1 isolates of known subtypes as well as those of 9 Taiwanese. These data provided the basis for subtyping the cosmopolitan type of HTLV-1 by amplification of envelope gene sequences and restriction fragment length polymorphism studies. A more extensive survey based upon this proposal was warranted.

Base Sequence↗
PubMed2000

The Na(+)-K(+)-ATPase alpha2 gene and trainability of cardiorespiratory endurance: the HERITAGE family study.

The Na(+)-K(+)-ATPase plays an important role in the maintenance of electrolyte balance in the working muscle and thus may contribute to endurance performance. This study aimed to investigate the associations between genetic variants at the Na(+)-K(+)-ATPase alpha2 locus and the response (Delta) of maximal oxygen consumption (VO(2 max)) and maximal power output (W(max)) to 20 wk of endurance training in 472 sedentary Caucasian subjects from 99 families. VO(2 max) and W(max) were measured during two maximal cycle ergometer exercise tests before and again after the training program, and restriction fragment length polymorphisms at the Na(+)-K(+)-ATPase alpha2 (exons 1 and 21-22 with Bgl II) gene were typed. Sibling-pair linkage analysis revealed marginal evidence for linkage between the alpha2 haplotype and DeltaVO(2 max) (P = 0.054) and stronger linkages between the alpha2 exon 21-22 marker (P = 0.005) and alpha2 haplotype (P = 0.003) and DeltaW(max). In the whole cohort, DeltaVO(2 max) in the 3.3-kb homozygotes of the exon 1 marker (n = 5) was 41% lower than in the 8.0/3.3-kb heterozygotes (n = 87) and 48% lower than in the 8.0-kb homozygotes (n = 380; P = 0.018, adjusted for age, gender, baseline VO(2 max), and body weight). Among offspring, 10.5/10.5-kb homozygotes (n = 14) of the exon 21-22 marker showed a 571 +/- 56 (SE) ml O(2)/min increase in VO(2 max), whereas the increases in the 10.5/4.3-kb (n = 93) and 4.3/4.3-kb (n = 187) genotypes were 442 +/- 22 and 410 +/- 15 ml O(2)/min, respectively (P = 0.017). These data suggest that genetic variation at the Na(+)-K(+)-ATPase alpha2 locus influences the trainability of VO(2 max) in sedentary Caucasian subjects.

Adaptation, Physiological↗
PubMed2005

Molecular marker assisted selection and pyramiding of two QTLs for fiber strength in upland cotton.

Based on two major QTLs that control high fiber strength which originated from an elite fiber germ-plasm line 7235 (Gossypium hiusutum L.), the efficiency of molecular marker-assisted selection (MAS) was investigated using two populations from pedigree selection and modified backcrossing pyramiding developed for the breeding purpose. Simian 3 (SM3), a widely planted variety in the Yangtze River Valley, and 7235 were used as parents to develop the two populations. In the two major QTLs for fiber strength from 7235, QTLfs-1 could explain more than 30% of the phenotypic variation (PV) in the (7235 x TM-1) F2 population. QTLfs-2 was at first identified in another super quality fiber line HS427-10 from (HS427-10 x TM-1) F2 population with 12.5% of PV explanation,which was further also identified in 7235 line but was non-allelic with QTLfs-1. The result of molecular marker-assisted selection for fiber strength showed that the genetic effect of the QTLfs-1 was stable under different environmental conditions, and its molecular marker-assisted selection showed significant selective efficiency among breeding populations with different genetic backgrounds. QTLfs-2 also showed high selective efficiency in advanced generation populations though its effect was a little lower than the former. When QTLfs-1 was selected simultaneously with 2 molecular markers with known genetic distance, the selection efficiency for the fiber strength was greatly increased. The pyramiding for two QTLs that control high fiber strength by MAS greatly improved the selection efficiency for cotton fiber strength. This report provides a successful example of MAS pyramiding for QTL for favorable traits in breeding programs.

Cotton Fiber↗
PubMed2003

The -174G allele of the interleukin-6 gene confers susceptibility to systemic arthritis in children: a multicenter study using simplex and multiplex juvenile idiopathic arthritis families.

OBJECTIVE: Levels of interleukin-6 (IL-6) have been shown to correlate with the fever and disease activity of systemic juvenile idiopathic arthritis (JIA). In a previous case-control study, a significant association between the IL-6 -174 nucleotide variant and systemic JIA was noted, and HeLa cell transfection assays show functional differences in levels of transcription of the IL-6 -174 alleles. The present study was undertaken to confirm the previous findings and to assess possible association with variations of the A(n)T(n) tract in the promoter. METHODS: We studied a cohort of JIA families from 3 countries, using transmission disequilibrium testing. Genotyping of the -174 nucleotide variant was done by restriction fragment length polymorphism, heteroduplex analysis, or allelic discrimination. The A(n)T(n) tract at -392 to -373 was typed using DNA sequencing. Statistical analysis was performed using the programs Transmit and EHplus. RESULTS: There was a significant excess transmission of the -174G allele in the systemic JIA families (P = 0.041). The excess transmission was only to systemic JIA patients with age at onset >5 years (P = 0.007). No significant association with the other subtypes was found. No A(n)T(n) alleles or -174/A(n)T(n) haplotypes were significantly associated with systemic JIA. CONCLUSION: This study confirms that the IL-6 -174 nucleotide variant is significantly associated with systemic JIA. The significant excess transmission to patients with age at onset >5 years but not to those with age at onset < or =5 years suggests that there may be genetic heterogeneity between the 2 groups.

Adolescent↗
PubMed2001

Markov chain Monte Carlo computation of confidence intervals for substitution-rate variation in proteins.

We suggest a method implemented in a computer program, immodestly dubbed TSUNAMI, that allows us to compare two homologous protein subfamilies with respect to the distribution of substitution rates along sequences. This study furthers our earlier work on a wavelet model of rate variation (1). The current approach allows sensitive detection of subtle discordances in the selection patterns between two protein subfamilies. In addition to performing fast computation of the maximum posterior probability estimates of the relative substitution rates, the method can select the most appropriate number of wavelet parameters for a particular dataset. TSUNAMI is based on a Markov chain Monte Carlo technique, and appears to be more applicable to larger datasets than is the full likelihood-based approach.

Amino Acid Substitution↗
PubMed2001

Individual differences in response to regular physical activity.

PURPOSE: The purpose of this review was to address the question of interindividual variation in responsiveness to regular exercise training and to define the contributions of age, sex, race, and pretraining phenotype level to this variability. METHODS: A literature review was conducted of the studies reporting interindividual variation in responsiveness to standardized and controlled exercise-training programs, and included an analysis of the contribution of age, sex, race, and initial phenotype values to the heterogeneity in VO(2max), high-density lipoprotein (HDL)-C and submaximal exercise, heart rate (HR), and systolic blood pressure (SBP) training responses in subjects from the HERITAGE Family Study. RESULTS: Several studies have shown marked individual differences in responsiveness to exercise training. For example, VO(2max) responses to standardized training programs have ranged from almost no gain up to 100% increase in large groups of sedentary individuals. A similar pattern of heterogeneity has been observed for other phenotypes. Data from the HERITAGE Family Study show that age, sex, and race have little impact on interindividual differences in training responses. On the other hand, the initial level of a phenotype is a major determinant of training response for some traits, such as submaximal exercise heart rate and blood pressure (BP) but has only a minor effect on others (e.g., VO(2max), HDL-C). The contribution of familial factors (shared environment and genetic factors) is supported by data on significant familial aggregation of training response phenotypes. CONCLUSIONS: There is strong evidence for considerable heterogeneity in the responsiveness to regular physical activity. Age, sex, and ethnic origin are not major determinants of human responses to regular physical activity, whereas the pretraining level of a phenotype has a considerable impact in some cases. Familial factors also contribute significantly to variability in training response.

Adult↗
PubMed2006

FLOWERING LOCUS C-dependent and -independent regulation of the circadian clock by the autonomous and vernalization pathways.

BACKGROUND: The circadian system drives pervasive biological rhythms in plants. Circadian clocks integrate endogenous timing information with environmental signals, in order to match rhythmic outputs to the local day/night cycle. Multiple signaling pathways affect the circadian system, in ways that are likely to be adaptively significant. Our previous studies of natural genetic variation in Arabidopsis thaliana accessions implicated FLOWERING LOCUS C (FLC) as a circadian-clock regulator. The MADS-box transcription factor FLC is best known as a regulator of flowering time. Its activity is regulated by many regulatory genes in the "autonomous" and vernalization-dependent flowering pathways. We tested whether these same pathways affect the circadian system. RESULTS: Genes in the autonomous flowering pathway, including FLC, were found to regulate circadian period in Arabidopsis. The mechanisms involved are similar, but not identical, to the control of flowering time. By mutant analyses, we demonstrate a graded effect of FLC expression upon circadian period. Related MADS-box genes had less effect on clock function. We also reveal an unexpected vernalization-dependent alteration of periodicity. CONCLUSION: This study has aided in the understanding of FLC's role in the clock, as it reveals that the network affecting circadian timing is partially overlapping with the floral-regulatory network. We also show a link between vernalization and circadian period. This finding may be of ecological relevance for developmental programming in other plant species.

Arabidopsis↗
PubMed2001

Insertion/deletion frequencies match those of point mutations in the hypervariable regions of the simian immunodeficiency virus surface envelope gene.

A method for encoding insertions and deletions (indels) has been developed and adapted to the SplitsTree program. Following phylogenetic reconstruction, the relative frequencies of indels were estimated for a large number of in vivo sequence sets corresponding to the env V1 hypervariable region of the simian immunodeficiency virus SIVmac251. The method allowed recovery of many point mutations hitherto lost due to gap stripping. Deletions were as frequent as transversions and were 4- to 8-fold more frequent than insertions, invariably duplications. The high proportion of deletions among mutation events suggests that lentivirus vectors may readily delete parts of their cargo.

Base Sequence↗
PubMedDate not supplied

Comparison of sequence differences in a variable 23S rRNA domain among sets of cryptic species of ciliated protozoa.

Studies were undertaken to discover the relative molecular distances separating some familiar forms of ciliated protozoa, and the genetic species they include. Sequences of 190 bases of the D2 domain of the large ribosomal nucleic acid molecule were obtained by polymerase chain reaction from protists of three distinctive groups of ciliated protozoa-Colpoda, Paramecium and Tetrahymena. Evolutionary trees were constructed for each set of sequences using the PHYLOGEN 1.0 string programs. All three groups of ciliates manifested large molecular diversity among strains difficult or impossible to distinguish morphologically. The largest single evolutionary distance within a group was the 75 differences separating Tetrahymena paravorax from the other tetrahymenids. The largest mean distance for a group was the 21.2 for the colpodids. In all the protist groups the large molecular diversity is obscured by morphological conservatism associated with constraints of ancient designs. The molecular diversity within morphotypes argues for long evolutionary coexistence of species differentiated from each other in significant physiological, ecological, or nutritional ways.

Animals↗
PubMed2003

GénoPlante-Info (GPI): a collection of databases and bioinformatics resources for plant genomics.

Génoplante is a partnership program between public French institutes (INRA, CIRAD, IRD and CNRS) and private companies (Biogemma, Bayer CropScience and Bioplante) that aims at developing genome analysis programs for crop species (corn, wheat, rapeseed, sunflower and pea) and model plants (Arabidopsis and rice). The outputs of these programs form a wealth of information (genomic sequence, transcriptome, proteome, allelic variability, mapping and synteny, and mutation data) and tools (databases, interfaces, analysis software), that are being integrated and made public at the public bioinformatics resource centre of Génoplante: GénoPlante-Info (GPI). This continuous flood of data and tools is regularly updated and will grow continuously during the coming two years. Access to the GPI databases and tools is available at http://genoplante-info.infobiogen.fr/.

Alleles↗