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European Gene Mapping Project (EUROGEM): breakpoint panels for human chromosomes based on the CEPH reference families. Centre d'Etude du Polymorphisme Humain.

Meiotic breakpoint panels for human chromosomes 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 14, 15, 17, 18, 20 and X were constructed from genotypes from the CEPH reference families. Each recombinant chromosome included has a breakpoint well-supported with reference to defined quantitative criteria. The panels were constructed at both a low-resolution, useful for a first-pass localization, and high-resolution, for a more precise placement. The availability of such panels will reduce the number of genotyping experiments necessary to order new polymorphisms with respect to existing genetic markers. This paper shows only a representative sample of the breakpoints detected. The complete data are available on the World Wide Web (URL http:/(/)www.icnet.uk/axp/hgr/eurogem++ +/HTML/data.html) or by anonymous ftp (ftp.gene.ucl.ac.uk in/pub/eurogem/maps/breakpoints).

Chromosome Mapping↗

A highly conserved genomic region in baculoviruses: sequence analysis of an 11.3 kbp DNA fragment (46.5-55.1 m.u.) of the Spodoptera exigua multicapsid nucleopolyhedrovirus.

A DNA fragment of 11.3 kilobase pairs (kbp) in size of the baculovirus Spodoptera exigua multicapsid nucleopolyhedrovirus (SeMNPV) genome (46.5 to 55.1 m.u.) was completely sequenced. Analysis of the sequence revealed eleven potential open reading frames (ORF). Ten of these ORFs showed significant amino acid identity to Autographa californica MNPV (AcMNPV) and Orgyia pseudotsugata MNPV (OpMNPV) genes p6.9, lef5, 38K, p19, p143, p25, p18, vp33, lef4, and vp39. One ORF (XC12) has no homolog in other baculoviruses and may be unique to SeMNPV. All but three of these putative genes are preceded by the consensus baculovirus late promoter element (5'-ATAAG-3'). The genetic organization and the putative map of transcripts of this fragment suggested that this region is highly similar to a region in AcMNPV fragment EcoRI-D. Comparison of the genetic organization of this 11.3 kbp fragment with the genomes of AcMNPV, OpMNPV, Bombyx mori NPV (BmNPV) and SeMNPV revealed that this region is highly conserved among baculovirus genomes. This is in contrast to the genetic organization of the polyhedrin-p10 region, which is much more diverged, but has been taken as point of reference to orient baculovirus physical maps. Through its diversity the latter region, however, would be an excellent candidate to determine baculovirus relatedness and phylogeny. The presence of conserved and diverged regions in baculovirus genomes with respect to gene order is reminiscent to the situation in other large DNA viruses, such as herpes- and poxviruses, where conserved central and diverged terminal parts are common characteristics. The role of this feature in the genomic organization of large DNA viruses is discussed with particular emphasis on virus replication and evolution.

Animals↗

Visual information processing of computed topographic electrical activity brain maps.

Effective display of computer-generated biomedical images draws on computer graphics and image processing, display technology and human factors, visual psychophysics and perception, cognitive psychology, and the new field of scientific data visualization. In converting from raw, acquired data to a visual display, developers need to know the limitations of the data and of the display technology. To obtain reliable inferences about the clinical or physiological state of the patient requires that the computer display be matched to the visual information-processing competence and limitations of human observers. The issues that should be considered by both developers and users of computer-based display technologies to enhance clinical performance in observation and diagnosis are surveyed with reference to electrical activity brain maps.

Brain↗

Leptospira species categorized by arbitrarily primed polymerase chain reaction (PCR) and by mapped restriction polymorphisms in PCR-amplified rRNA genes.

Reference strains from 48 selected serovars representing eight species of Leptospira were examined by two polymerase chain reaction (PCR)-based strategies. First, mapped restriction site polymorphisms (MRSP) were examined in PCR products from portions of rrs (16S rRNA gene) and rrl (23S rRNA gene). Twenty MRSP and 2 length polymorphisms were used to group reference strains into 16 MRSP profiles. Species assignments were consistent with those obtained by a second method, genomic fingerprinting with arbitrarily primed PCR, in which strains within a species were characterized by many shared arbitrarily primed PCR products. The results of both of these methods were in general agreement with those of previous studies that used DNA-DNA relatedness and confirmed the high level of divergence among the recognized species of Leptospira. However, Leptospira meyeri serovar ranarum and evansi strains were indistinguishable from some strains of Leptospira interrogans sensu stricto. Intervening sequences of about 485 to 740 bp were located near base 1230 in rrl of some strains.

Base Sequence↗

Computerized topo-EEG spectral maps: difficulties and perspectives.

An electric potential measurement tells us only about the difference between two electrode locations. When prior experiments or present measurements prove that an electrode's location is inactive (especially in 'mono-polar' or scalp-to-reference technique), then EEG records and EEG maps can be interpreted regionally near each electrode location. Topographical mapping requires spatial interpolation which is one factor involved in spatial resolution. The interpolation algorithm has been studied by changing the power exponent n of the interelectrode distance d. When n is close to zero, interpolated values are all equal to the average of the four electric potential measurement Vs bounding the quadrilateral in which the interpolated points of the EEG map are located. When n is very high (n = 20 or higher), the values are essentially equal to the V which is at the minimum distance d. For n = 1, the map seems unlikely to represent the true scalp field. The choice between n = 2 and n = 3 is difficult, but n = 3 EEG mapping looks better (more plausible) and is our regular choice. The choice of recording/reporting method has also been studied. If the quantitative EEG map is linearly calculated from observations, the interpretation of record activity resulting from charge separation near the non-reference electrode attached to a particular channel is only possible when inactivity can be assured. This is completely different when the quantity mapped is not linearly calculated from observations (like power values or rms amplitudes in microvolts).(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Mapping↗

A structural model of human erythrocyte spectrin. Alignment of chemical and functional domains.

Proteolytic susceptibility has been used to probe the structure of human erythrocyte spectrin. Nine unique polypeptide segments have been defined by mild trypsin digestion (0 degrees C) and analyzed by two-dimensional peptide mapping techniques. These peptide segments, referred to operationally as chemical domains, exhibited varying degrees of sensitivity to further proteolytic cleavage. One region (beta I) which contained the phosphorylated amino acids of the beta subunit was quite sensitive to proteolysis and was rapidly degraded to numerous small peptides. Overlap peptides produced by enzymatic and chemical cleavages were used to align each domain in the appropriate spectrin subunit. The molecular weights of the largest unique peptides from both subunits sum to the approximate weight of the intact molecule. Similarly, summation of the two-dimensional peptide maps of the intermediate sized peptides approximates the two-dimensional maps of the intact spectrin subunits, indicating that most or all of the molecule is represented. These results suggest that spectrin is composed of multiple, ordered, largely alpha-helical domains that are connected by small protease-sensitive segments. A comprehensive structural model is presented.

Electrophoresis, Cellulose Acetate↗

A 2-cM genetic linkage map of human chromosome 7p that includes 47 loci.

A new high-resolution genetic linkage map for human chromosome 7p has been constructed. The map is composed of 47 loci (54 polymorphic systems), 19 of which are uniquely placed with odds of at least 1000:1. Four genes are represented, including glucokinase (GCK, ATP:D-hexose-6-phosphotransferase, EC 2.7.1.2) which was mapped via a (CA)n dinucleotide repeat polymorphism. The sex-average map measures 94.4 cM and the male and female maps measure 73.2 and 116.1 cM, respectively. We believe that the genetic map extends nearly the full length of the short arm of chromosome 7 since a centromere marker has been incorporated, and the most distal marker, D7S21, has been cytogenetically localized by in situ hybridization to 7p22-pter. The average marker spacing is 2 cM, and the largest interval between uniquely placed markers is 13 cM (sex-average map). Overall, female recombination was observed to be about 1.5 times that of males, and a statistically significant sex-specific recombination frequency was found for a single interval. The map is based on genotypic data gathered from 40 CEPH reference pedigrees and was constructed using the CRI-MAP program package. The map presented here represents a combined and substantially expanded dataset compared to previously published chromosome 7 maps, and it will serve as a "baseline" genetic map that should prove useful for future efforts to develop a 1-cM map and for construction of a contiguous clone-based physical map for this chromosome.

Base Sequence↗

New methods to identify and rank high pedestrian crash zones: an illustration.

Identifying and ranking high pedestrian crash zones plays a key role in developing efficient and effective strategies to enhance pedestrian safety. This paper presents (1) a Geographical Information Systems (GIS) methodology to study the spatial patterns of pedestrian crashes in order to identify high pedestrian crash zones, and (2) an evaluation of methods to rank these high pedestrian crash zones. The GIS based methodology to identify high pedestrian crash zones includes geocoding crash data, creating crash concentration maps, and then identifying high pedestrian crash zones. Two methods generally used to create crash concentration maps based on density values are the Simple Method and the Kernel Method. Ranking methods such as crash frequency, crash density, and crash rate, as well as composite methods such as the sum-of-the-ranks and the crash score methods are used to rank the selected high pedestrian crash zones. The use of this methodology and ranking methods for high pedestrian crash zones are illustrated using the Las Vegas metropolitan area as the study area. Crash data collected for a 5-year period (1998-2002) were address matched using the street name/reference street name intersection location reference system. A crash concentration map was then created using the Kernel Method as it facilitates the creation of a smooth density surface when compared to the Simple Method. Twenty-two linear high crash zones and seven circular high crash zones were then identified. The GIS based methodology reduced the subjectivity in the analysis process. Results obtained from the evaluation of methods to rank high pedestrian crash zones show a significant variation in ranking when individual methods were considered. However, rankings of high pedestrian crash zones were relatively consistent with little to no variation when the sum-of-the-ranks method and the crash score method were used. Thus, these composite methods are recommended for use in ranking high pedestrian crash zones instead of individual methods.

Accidents, Traffic↗

A database and tool, IM Browser, for exploring and integrating emerging gene and protein interaction data for Drosophila.

BACKGROUND: Biological processes are mediated by networks of interacting genes and proteins. Efforts to map and understand these networks are resulting in the proliferation of interaction data derived from both experimental and computational techniques for a number of organisms. The volume of this data combined with the variety of specific forms it can take has created a need for comprehensive databases that include all of the available data sets, and for exploration tools to facilitate data integration and analysis. One powerful paradigm for the navigation and analysis of interaction data is an interaction graph or map that represents proteins or genes as nodes linked by interactions. Several programs have been developed for graphical representation and analysis of interaction data, yet there remains a need for alternative programs that can provide casual users with rapid easy access to many existing and emerging data sets. DESCRIPTION: Here we describe a comprehensive database of Drosophila gene and protein interactions collected from a variety of sources, including low and high throughput screens, genetic interactions, and computational predictions. We also present a program for exploring multiple interaction data sets and for combining data from different sources. The program, referred to as the Interaction Map (IM) Browser, is a web-based application for searching and visualizing interaction data stored in a relational database system. Use of the application requires no downloads and minimal user configuration or training, thereby enabling rapid initial access to interaction data. IM Browser was designed to readily accommodate and integrate new types of interaction data as it becomes available. Moreover, all information associated with interaction measurements or predictions and the genes or proteins involved are accessible to the user. This allows combined searches and analyses based on either common or technique-specific attributes. The data can be visualized as an editable graph and all or part of the data can be downloaded for further analysis with other tools for specific applications. The database is available at http://proteome.wayne.edu/PIMdb.html CONCLUSION: The Drosophila Interactions Database described here places a variety of disparate data into one easily accessible location. The database has a simple structure that maintains all relevant information about how each interaction was determined. The IM Browser provides easy, complete access to this database and could readily be used to publish other sets of interaction data. By providing access to all of the available information from a variety of data types, the program will also facilitate advanced computational analyses.

Database Management Systems↗

Sensory stimulation accelerates dopamine release in the basal ganglia.

We report herein the modulation of dopamine release in the basal ganglia during peripheral electrical stimulation in animals. The endogenous dopamine release during electrical stimulation was measured in anesthetized cats by positron emission tomography (PET) using the D2 receptor agonist [11C]-raclopride. Binding potential (BP) parametric maps were calculated using a simplified reference region model. The regional dopamine release evoked by electrical stimulation was estimated both by region of interest (ROI) analysis and statistical parametric mapping (SPM 99). Both ROI analysis and statistical parametric mapping showed significant release of endogenous dopamine in the nucleus accumbens and the striatum contralateral to the stimulated side as compared to the resting condition as well as the ipsilateral side. Accordingly, we suggest that the activity of the dopaminergic neurons in the midbrain projecting to the nucleus accumbens and the striatum is modulated by the input from the afferent nerves. This provides an in vivo evidence for the importance of the basal ganglia in the processing of peripheral information required for normal movement. This may also explain the clinically observed sensory system abnormalities in patients with movement disorders.

Animals↗

The genetic map and comparative analysis with the physical map of Trypanosoma brucei.

Trypanosoma brucei is the causative agent of African sleeping sickness in humans and contributes to the debilitating disease 'Nagana' in cattle. To date we know little about the genes that determine drug resistance, host specificity, pathogenesis and virulence in these parasites. The availability of the complete genome sequence and the ability of the parasite to undergo genetic exchange have allowed genetic investigations into this parasite and here we report the first genetic map of T.brucei for the genome reference stock TREU 927, comprising of 182 markers and 11 major linkage groups, that correspond to the 11 previously identified chromosomes. The genetic map provides 90% probability of a marker being 11 cM from any given locus. Its comparison to the available physical map has revealed the average physical size of a recombination unit to be 15.6 Kb/cM. The genetic map coupled with the genome sequence and the ability to undertake crosses presents a new approach to identifying genes relevant to the disease and its prevention in this important pathogen through forward genetic analysis and positional cloning.

Animals↗

Sequence-tagged microsatellite sites as markers in chicken reference and resource populations.

Two chicken genomic libraries were screened for the presence of poly(TG/AC) microsatellite tracts. The number of positive clones was low, confirming the low frequency of such microsatellites in the chicken genome relative to mammalian genomes. Polymorphism of 29 microsatellite tracts, comprising 11 from the library screening and 18 obtained from GenBank, was examined in the East Lansing and Compton reference families, in a resource population formed by a cross between a single White Rock broiler and inbred Leghorn females, and in a panel of birds from five layer stocks. Twenty microsatellites, primarily of the poly(TG/AC) type, were polymorphic in at least one of the populations. Thirteen of the microsatellites were polymorphic in the East Lansing reference family and 13 were also polymorphic in the resource population, confirming that the genetic distance between White Rock and White Leghorn is about as great as between Jungle fowl and White Leghorn. Only six microsatellites were polymorphic in the Compton reference family, formed by a cross between two White Leghorn strains. Twelve of the microsatellites were mapped in the East Lansing and/or Compton reference families. These were well dispersed among the various linkage groups and did not show any indications of terminal clustering.

Animals↗

Functional MRI near vascular anomalies: comparison of cavernoma and arteriovenous malformation.

BACKGROUND AND PURPOSE: Mapping of eloquent cortex using blood-oxygen-level-dependent (BOLD) contrast functional MRI (fMRI) has rapidly gained acceptance as part of the evaluation of patients being considered for neurosurgical interventions. The BOLD signal measures local susceptibility in the blood, which can change during periods of increased neuronal activation as a result of alteration in blood flow and cerebral oxygen utilisation. Vascular anomalies could influence the BOLD signal via their effects on both blood flow and susceptibility. METHODS: In the present study we have compared the fMRI signal associated with functional activation near arteriovenous malformations and cavernomas in a group of patients referred for pre-surgical mapping of eloquent cortex. RESULTS: The magnitude of the BOLD signal was not different for the cavernoma group and the AVM group (mean percentage signal change 6.3% vs. 5.5%). For subjects with cavernoma, there was an increase in cavernoma volume on the functional images compared to T1-weighted anatomical images (mean 570%), and a BOLD signal was only detected outside the enlarged cavernoma. CONCLUSION: The findings show that susceptibility effects associated with cavernoma, most likely due to hemosiderin deposition, can result in an apparent increase in the separation between the BOLD signal and the cavernoma itself. This could lead to falsely high levels of surgical confidence during neurosurgical resection. Differential patterns of blood flow associated with cavernoma and AVM do not appear to significantly affect the BOLD signal magnitude.

Adolescent↗

A linkage map with microsatellites isolated from swine flow-sorted chromosome 11.

We have developed a simple and efficient method to construct partial libraries of swine Chromosome (Chr) 11, starting with only 300 flow-sorted copies. DNA is amplified by PARM-PCR with primer containing at the 5'-end the sequence AGCU-. After amplification, digestion of PCR products with uracil DNA glycosylase generates cohesive ends corresponding to the SstI site. The amplified fragments can then be ligated in vector linearized with the SstI enzyme. Using five different primers, we PARM-PCR amplified and cloned swine Chr 11 DNA. These chromosome-specific libraries have been used to develop 14 different (TG)n microsatellites. Ten of these markers were assigned to Chr 11 by PCR analysis of a panel of Pig-Rodent somatic hybrids and by linkage analysis of the 171 individuals of the PiGMaP reference families. A complete linkage map of 147 cM of this chromosome was then realized by integrating existing markers.

Animals↗

Predicting the distribution of urinary schistosomiasis in Tanzania using satellite sensor data.

In this paper, remotely sensed (RS) satellite sensor environmental data, using logistic regression, are used to develop prediction maps of the probability of having infection prevalence exceeding 50%, and warranting mass treatment according to World Health Organization (WHO) guidelines. The model was developed using data from one area of coastal Tanzania and validated with independent data from different areas of the country. Receiver operating characteristic (ROC) analysis was used to evaluate the model's predictive performance. The model allows reasonable discrimination between high and low prevalence schools, at least within those geographical areas in which they were originally developed, and performs reasonably well in other coastal areas, but performs poorly by comparison in the Great Lakes area of Tanzania. These results may be explained by reference to an ecological zone map based on RS-derived environmental data. This map suggests that areas where the model reliably predicts a high prevalence of schistosomiasis fall within the same ecological zone, which has common intermediate-host snail species responsible for transmission. By contrast, the model's performance is poor near Lake Victoria, which is in a different ecological zone with different snail species. The ecological map can potentially define a template for those areas where existing models can be applied, and highlight areas where further data and models are required. The developed model was then used to provide estimates of the number of schoolchildren at risk of high prevalence and associated programme costs.

Adolescent↗

Potential role of body surface ECG mapping for localization of atrial fibrillation trigger sites.

Catheter ablation has revolutionized the clinical management of atrial fibrillation (AF) by offering a curative treatment option for this highly prevalent arrhythmia. Ablation therapy is aimed at electrical isolation of the pulmonary veins (PVs) as a means to prevent rapidly firing focal activation within the PVs from penetrating into the left atrium (LA) and initiate reentrant wavelet propagation. However, non-PV AF trigger sites may be present and lead to unsuccessful ablation or post-ablation AF recurrences. Infrequent trigger firing and the difficulty or inability to induce focal trigger activity in the electrophysiology laboratory limits invasive catheter-based mapping of non-PV trigger sites. Identification of AF trigger sites using the surface electrocardiogram (ECG) P wave morphology is feasible but conventional 12-lead scalar recordings do not offer the resolving power to provide discrete regional localization to potentially target catheter ablation. The present paper includes a review of preliminary clinical data on the use of a 65-lead ECG mapping system (Resolution Medical, Inc) for the non-invasive localization of AF trigger sites. This method utilizes a unique previously developed reference database of 34 mean paced P wave integral map patterns which are each specific to activation arising from a discrete segment in the LA and right atrium (RA). Trigger site localization is obtained by matching the P wave integral map morphology of a premature atrial contraction (PAC) with the reference database of 34 mean paced P wave integral map patterns.

Algorithms↗

The molecular cloning of the gene encoding the Escherichia coli 75-kDa helicase and the determination of its nucleotide sequence and gentic map position.

A previously unreported DNA unwinding enzyme, referred to as the 75-kDa helicase, was recently purified from Escherichia coli cell extracts and biochemically characterized (Wood, E. R., and Matson, S. W. (1987) J. Biol. Chem. 262, 15269-15276). In order to initiate the genetic analysis of the 75-kDa helicase, the gene encoding this enzyme was cloned. DNA sequencing confirmed the identity of the gene since the predicted amino acid sequence of the encoded polypeptide precisely matched the sequence of the first 27 NH2-terminal amino acid residues of the 75-kDa helicase as determined by peptide sequencing. The predicted amino acid sequence of the 75-kDa helicase is similar in several regions to the amino acid sequences of two other E. coli helicases, Rep protein and helicase II. The gene encoding the 75-kDa helicase was mapped to 22 min on the E. coli chromosome. We propose that this newly defined locus be referred to as helD, and, to avoid confusion with other E. coli helicases with a similar molecular size, we propose that the 75-kDa helicase be referred to as helicase IV.

Adenosine Triphosphatases↗

A comprehensive microsatellite linkage map of the chicken genome.

A comprehensive linkage map of the chicken genome has been developed by segregation analysis of 430 microsatellite markers within a cross between two extreme broiler lines. The population used to construct the linkage map consists of 10 families with a total of 458 F2 individuals. The number of informative meioses per marker varied from 100 to 900 with an average of 400. The markers were placed into 27 autosomal linkage groups and a Z-chromosome-specific linkage group. In addition, 6 markers were unlinked, 1 of which was Z chromosome specific. The coverage within linkage groups is 3062 cM. Although, as in other species, the genetic map of the heterogametic sex (female) is shorter than the genetic map of the homogametic sex (male), the overall difference in length is small (1.15%). Forty-five of the markers represent identified genes or ESTs. Database homology searches with the anonymous markers resulted in the identification of a further 9 genes, bringing the total number of genes/ESTs on the current map to 54. The mapping of these genes led to the identification of two new regions of conserved synteny between human and chicken and confirmed other previously identified regions of conserved synteny between human and chicken. The linkage map has 210 markers in common with the linkage maps based on the East Lansing and Compton reference populations, and most of the corresponding linkage groups in the different maps can be readily aligned.

Animals↗