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A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat.

The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, the genetic infrastructure required for connecting phenotype and genotype in the rat is currently incomplete. Here, we report the construction and integration of two genomic maps: a dense genetic linkage map of the rat and the first radiation hybrid (RH) map of the rat. The genetic map was constructed in two F2 intercrosses (SHRSP x BN and FHH x ACI), containing a total of 4736 simple sequence length polymorphism (SSLP) markers. Allele sizes for 4328 of the genetic markers were characterized in 48 of the most commonly used inbred strains. The RH map is a lod >/= 3 framework map, including 983 SSLPs, thereby allowing integration with markers on various genetic maps and with markers mapped on the RH panel. Together, the maps provide an integrated reference to >3000 genes and ESTs and >8500 genetic markers (5211 of our SSLPs and >3500 SSLPs developed by other groups). [Bihoreau et al. (1997); James and Tanigami, RHdb (http:www.ebi.ac.uk/RHdb/index.html); Wilder (http://www.nih.gov/niams/scientific/ratgbase); Serikawa et al. (1992); RATMAP server (http://ratmap.gen.gu.se)] RH maps (v. 2.0) have been posted on our web sites at http://goliath.ifrc.mcw.edu/LGR/index.html or http://curatools.curagen.com/ratmap. Both web sites provide an RH mapping server where investigators can localize their own RH vectors relative to this map. The raw data have been deposited in the RHdb database. Taken together, these maps provide the basic tools for rat genomics. The RH map provides the means to rapidly localize genetic markers, genes, and ESTs within the rat genome. These maps provide the basic tools for rat genomics. They will facilitate studies of multifactorial disease and functional genomics, allow construction of physical maps, and provide a scaffold for both directed and large-scale sequencing efforts and comparative genomics in this important experimental organism.

Alleles↗

Application of self-organizing maps for the detection and classification of human blood plasma lipoprotein lipid profiles on the basis of 1H NMR spectroscopy data.

Efficient and relevant classification of clinical findings, i.e. diagnostic decision making, poses a major challenge in medicine. In relation to biomedical NMR spectroscopy the problem of classification is often accompanied by complex, heavily overlapping information. Self-organizing map (SOM) analysis has been successfully applied in many areas of research and was thus also considered as a potential tool for NMR data analysis. In this paper we demonstrate how SOM analysis can be used for automated NMR data classification. Our goal was analysis of plasma lipoprotein lipids, a complex but biochemically well understood and specified system. The results illustrate that clinically relevant lipid classifications can be obtained from the SOM analysis of 1H NMR spectral information alone. The resulting maps were calibrated using independent biochemical lipid analyses and were found to produce excellent clustering of the plasma samples into clinically useful groups: normal, type IIa, IIb and IV hyperlipidaemias. In addition to this traditional classification, we also present results from SOM analysis in which the reference vectors of the map were calibrated for plasma total cholesterol and triglycerides and high and low density lipoprotein C; the plasma lipid parameters that are currently considered as the most useful indicators of coronary heart disease risk. In all, the present results indicate that SOM analysis can cope well with complex NMR spectral information and is thus likely to have an independent role in the area of biomedical NMR data analysis.

Cholesterol↗

Microsatellites in the HLA region: 1999 update.

In this third update of a series of reviews on microsatellites in the HLA region or close to it we report 155 microsatellites, corresponding to 51 newly described markers, in addition to the 103 reported in the 1997 and 1998 reviews. This work is based both on a literature review and on data publicly available in molecular databases on the internet (http://www.gdb.org; http://bioinfo.weizmann.ac.il/cards/; http://cedar.genetics.soton.ac.uk/) up to September 1999. Thanks to numerous studies involving major histocompatibility complex (MHC) microsatellites, documentation on HLA region is proposed, including information on microsatellites described through MHC sequence projects and presenting documented location, polymorphism and amplification condition, together with additional information on previously described microsatellites when available and information on data in the literature regarding gametic associations between HLA region loci and alleles and microsatellite alleles. As basic information are presented various documents: i) a table showing the following characteristics of the 155 microsatellites: name, localisation, polymorphism, primer sequences, reference; ii) an integrated map of some HLA region genes and the 155 microsatellites considered; and iii) a summary table on HLA and microsatellites association patterns. In addition, an overview on HLA microsatellite analysis application is presented, with a special focus on disease genetics studies in the form of recent references where the use of microsatellites of the HLA region was a key tool. This review aims at providing the human immunogenetics community with a tool for helping optimal choice of microsatellites to be used in various studies.

Evolution, Molecular↗

Genetic and physical mapping of five novel microsatellite markers on human Xp21.1-p11.22.

Five polymorphic CA-dinucleotide repeats, identified in cosmids from the short arm of the human X chromosome, have been characterized and localized to Xp21.1 (DXS572), Xp11.4 (DXS556, DXS574), and Xp11.22-p11.23 (DXS722, DXS573). Genetic mapping with respect to five reference markers that include the gene for CGD (CYBB in Xp21.1), complemented by physical mapping information, has indicated the order tel-DXS572-CYBB-DXS1110-DXS556-DXS574-D XS7-DXS426-DXS722-DXS573-DXS255-cen.

Animals↗

Auditory cortex: comparative aspects of maps and plasticity.

Much recent work in the field of auditory cortex analysis consists of an intensified search for complex sound representation and sound localization mechanisms using tonotopic maps as a frame of reference. Mammalian species rely on parallel processing in multiple tonotopic and non-tonotopic maps but show different degrees of unit complexity, and orderly representation of acoustic dimensions in such maps depending on the predictability of sounds in their environment. Birds appear to rely chiefly on one tonotopic map which harbours multidimensional complex representations. During development and after partial hearing loss, tonotopic organization changes in a predictable manner. Learning also modifies the spatial representation of sounds and even modifies tonotopic organization, but the spatial rules involved in this process have not yet emerged.

Animals↗

Combined AFLP and RFLP mapping in two hexaploid oat recombinant inbred populations.

A combined RFLP and AFLP map was constructed for hexaploid oat (Avena spp.). The segregation of AFLP markers was scored in two hexaploid oat recombinant inbred line (RIL) populations, the 'Kanota' x 'Ogle' RFLP population, and a population derived from 'Clintland64' and 'IL86-5698', barley yellow dwarf virus (BYDV)-sensitive and BYDV-tolerant lines, respectively. More than 300 AFLP markers were scored in each population, of which 97 could be scored in both populations. AFLP markers were linked to RFLP markers in 32 of 36 'Kanota' x 'Ogle' RFLP linkage groups. The addition of the AFLP markers to the 'Kanota' x 'Ogle' RFLP data set combined markers from four pairs of linkage groups and increased the size of the map from 1402 cM to 2351 cM. Thirty linkage groups were observed in the 'Clintland64' x 'IL86-5698' population, two of which could be consolidated by comparing the maps from both populations. The AFLP and RFLP markers showed very similar distributions in the 'Kanota' x 'Ogle' population with a tendency of each type of marker to cluster with markers of the same type. The placement of a set of AFLP markers on the 'Kanota' x 'Ogle' linkage map will enrich the RFLP map and allow others to relate AFLP markers for agronomically important genes to the reference 'Kanota' x 'Ogle' linkage map.

Avena↗

Scaffolding and protein interactions in MAP kinase modules.

MAP kinases are a family of protein kinases that are ubiquitously expressed and play roles in most signal transduction pathways. They are activated within protein kinase cascades consisting of at least three kinases acting in series. In many, if not all cases, the three-kinase cascade, conveniently referred to as a MAP kinase module, is organized on scaffolds with a variety of forms and functions. This review discusses similarities and differences in scaffolding proteins and mechanisms in yeast, flies, worms and mammals.

Animals↗

Mental maps in memory retrieval and comprehension.

How do people use spatial information stored in maps? This question has been explored in a number of domains, such as memory and language comprehension, with differing results. Some studies of how experimentally learned maps are organised in memory, using primed recognition, have found temporal information to influence mental map organisation. In contrast, studies of narrative comprehension, using probe identification and anaphoric reading times, have observed spatial effects. This study combines these two research traditions and shows that the organisation observed in long-term memory differs from the organisation in narrative comprehension, even when both tasks refer to the same map.

Cognition↗

Spatial confidentiality and GIS: re-engineering mortality locations from published maps about Hurricane Katrina.

BACKGROUND: Geographic Information Systems (GIS) can provide valuable insight into patterns of human activity. Online spatial display applications, such as Google Earth, can democratise this information by disseminating it to the general public. Although this is a generally positive advance for society, there is a legitimate concern involving the disclosure of confidential information through spatial display. Although guidelines exist for aggregated data, little has been written concerning the display of point level information. The concern is that a map containing points representing cases of cancer or an infectious disease, could be re-engineered back to identify an actual residence. This risk is investigated using point mortality locations from Hurricane Katrina re-engineered from a map published in the Baton Rouge Advocate newspaper, and a field team validating these residences using search and rescue building markings. RESULTS: We show that the residence of an individual, visualized as a generalized point covering approximately one and half city blocks on a map, can be re-engineered back to identify the actual house location, or at least a close neighbour, even if the map contains little spatial reference information. The degree of re-engineering success is also shown to depend on the urban characteristic of the neighborhood. CONCLUSION: The results in this paper suggest a need to re-evaluate current guidelines for the display of point (address level) data. Examples of other point maps displaying health data extracted from the academic literature are presented where a similar re-engineering approach might cause concern with respect to violating confidentiality. More research is also needed into the role urban structure plays in the accuracy of re-engineering. We suggest that health and spatial scientists should be proactive and suggest a series of point level spatial confidentiality guidelines before governmental decisions are made which may be reactionary toward the threat of revealing confidential information, thereby imposing draconian limits on research using a GIS.

Confidentiality↗

[Statistical models for spatial analysis in parasitology].

The simplest way to study the spatial pattern of a disease is the geographical representation of its cases (or some indicators of them) over a map. Maps based on raw data are generally "wrong" since they do not take into consideration for sampling errors. Indeed, the observed differences between areas (or points in the map) are not directly interpretable, as they derive from the composition of true, structural differences and of the noise deriving from the sampling process. This problem is well known in human epidemiology, and several solutions have been proposed to filter the signal from the noise. These statistical methods are usually referred to as Disease Mapping. In geographical analysis a first goal is to evaluate the statistical significance of the heterogeneity between areas (or points). If the test indicates rejection of the hypothesis of homogeneity the following task is to study the spatial pattern of the disease. The spatial variability of risk is usually decomposed into two terms: a spatially structured (clustering) and a non spatially structured (heterogeneity) one. The heterogeneity term reflects spatial variability due to intrinsic characteristics of the sampling units (e.g. igienic conditions of farms), while the clustering term models the association due to proximity between sampling units, that usually depends on ecological conditions that vary over the study area and that affect in similar way breedings that are close to each other. Hierarchical bayesian models are the main tool to make inference over the clustering and heterogeneity components. The results are based on the marginal posterior distributions of the parameters of the model, that are approximated by Monte Carlo Markov Chain methods. Different models can be defined depending on the terms that are considered, namely a model with only the clustering term, a model with only the heterogeneity term and a model where both are included. Model selection criteria based on a compromise between degree of complexity and goodness of fit are then needed to discriminate among them, because each specification has a different biological meaning. Our aim is to demonstrate that these techniques can be used to study the geographical distribution of a parasite infection. Our analyses are based on data collected in 142 farms of the province of Latina. In each breeding a fixed number of sheeps has been sampled (20) and checked for the presence of C. daubneyi. We have specified a Binomial model for the proportion of infected animals in each breeding. The heterogeneity component is modelled in a standard way, while we have used different prior specifications for the clustering term to show how they affect the results. When we use the usual specification also for clustering, the two models show a completely different spatial pattern of infection, probably because the intrinsic spatial structure of the clustering term tend to bias our inferences. The selection criterion indicates in this case the heterogeneity model as the "best" one. However, if we modify the prior so that a lower degree of spatial interaction is assumed, the clustering model is less complex and its goodness of fit better and it should be preferred.

Animal Husbandry↗

A somatic cell hybrid panel and DNA probes for physical mapping of human chromosome 7p.

To identify by reverse genetics genes on the short arm of human chromosome 7 expected to be involved in the regulation of human craniofacial and limb development, we have set up a human mouse somatic cell hybrid panel that divides 7p into 9 fragments. The breakpoints are defined by deletions or translocations involving one chromosome 7 in the cells of the human cell fusion partners. Particularly densely covered with these cytogenetic anchor points is the proximal area of 7p within and around 7p13. The number of cytogenetic mapping points within proximal 7p could be increased by four, using two diploid human cell lines with small interstitial deletions in this region for dosage studies. We used Southern blots of this panel to assign to 7q or subregions of 7p more than 300 arbitrary DNA probes or genes that provide reference points for physical mapping of 7p. Three reciprocal translocations with one of the breakpoints in 7p13 mark the location of a gene involved in Greig cephalopolysyndactyly syndrome. To define an area in which we could identify candidates for this developmental gene, we established a macrorestriction map using probes flanking the putative gene region. The Greig translocations were found to be located within a 630-kb NotI restriction fragment.

Animals↗

Reliability of functional MR imaging with word-generation tasks for mapping Broca's area.

BACKGROUND AND PURPOSE: Functional MR (fMR) imaging of word generation has been used to map Broca's area in some patients selected for craniotomy. The purpose of this study was to measure the reliability, precision, and accuracy of word-generation tasks to identify Broca's area. METHODS: The Brodmann areas activated during performance of word-generation tasks were tabulated in 34 consecutive patients referred for fMR imaging mapping of language areas. In patients performing two iterations of the letter word-generation tasks, test-retest reliability was quantified by using the concurrence ratio (CR), or the number of voxels activated by each iteration in proportion to the average number of voxels activated from both iterations of the task. Among patients who also underwent category or antonym word generation or both, the similarity of the activation from each task was assessed with the CR. In patients who underwent electrocortical stimulation (ECS) mapping of speech function during craniotomy while awake, the sites with speech function were compared with the locations of activation found during fMR imaging of word generation. RESULTS: In 31 of 34 patients, activation was identified in the inferior frontal gyri or middle frontal gyri or both in Brodmann areas 9, 44, 45, or 46, unilaterally or bilaterally, with one or more of the tasks. Activation was noted in the same gyri when the patient performed a second iteration of the letter word-generation task or second task. The CR for pixel precision in a single section averaged 49%. In patients who underwent craniotomy while awake, speech areas located with ECS coincided with areas of the brain activated during a word-generation task. CONCLUSION: fMR imaging with word-generation tasks produces technically satisfactory maps of Broca's area, which localize the area accurately and reliably.

Brain Mapping↗

First comprehensive low-density horse linkage map based on two 3-generation, full-sibling, cross-bred horse reference families.

Two 3-generation full-sibling reference families have been produced and form a unique resource for genetic linkage mapping studies in the horse. The F(2) generations, now comprising 61 individuals, consist of 28- to 32-day-old embryos removed nonsurgically from two pairs of identical twin mares. The same stallion sired all F(2)s such that the two full-sibling families are half-sibling with respect to each other. The families are crossbred to maximize levels of heterozygosity and include Arabian, Thoroughbred, Welsh Cob, and Icelandic Horse breeds. Milligram quantities of DNA have been isolated from each embryo and from blood samples of the parents and grandparents. The families have been genotyped with 353 equine microsatellites and 6 biallelic markers, and 42 linkage groups were formed. In addition, the physical location of 85 of the markers is known, and this has allowed 37 linkage groups to be anchored to the physical map. The inclusion of dams in the genotyping analysis has allowed the generation of a genetic map of the X chromosome. Markers have been assigned to all 31 autosomes and the X chromosome. The average interval between markers on the map is 10.5 cM, and the linkage groups collectively span 1780 cM. The results demonstrate the benefits for horse linkage mapping studies of genotyping on these unique full-sibling families, which comprise relatively few individuals, by the generation of a comprehensive low-density map of the horse genome.

Animals↗

Identification of transcriptome SNPs between Xiphophorus lines and species for assessing allele specific gene expression within F₁ interspecies hybrids.

Variations in gene expression are essential for the evolution of novel phenotypes and for speciation. Studying allelic specific gene expression (ASGE) within interspecies hybrids provides a unique opportunity to reveal underlying mechanisms of genetic variation. Using Xiphophorus interspecies hybrid fishes and high-throughput next generation sequencing technology, we were able to assess variations between two closely related vertebrate species, Xiphophorus maculatus and Xiphophorus couchianus, and their F(1) interspecies hybrids. We constructed transcriptome-wide SNP polymorphism sets between two highly inbred X. maculatus lines (JP 163 A and B), and between X. maculatus and a second species, X. couchianus. The X. maculatus JP 163 A and B parental lines have been separated in the laboratory for ≈70 years and we were able to identify SNPs at a resolution of 1 SNP per 49 kb of transcriptome. In contrast, SNP polymorphisms between X. couchianus and X. maculatus species, which diverged ≈5-10 million years ago, were identified about every 700 bp. Using 6524 transcripts with identified SNPs between the two parental species (X. maculatus and X. couchianus), we mapped RNA-seq reads to determine ASGE within F(1) interspecies hybrids. We developed an in silico X. couchianus transcriptome by replacing 90,788 SNP bases for X. maculatus transcriptome with the consensus X. couchianus SNP bases and provide evidence that this procedure overcomes read mapping biases. Employment of the in silico reference transcriptome and tolerating 5 mismatches during read mapping allow direct assessment of ASGE in the F(1) interspecies hybrids. Overall, these results show that Xiphophorus is a tractable vertebrate experimental model to investigate how genetic variations that occur during speciation may affect gene interactions and the regulation of gene expression.

Alleles↗

Mapping variables.

This paper describes Mapping Variables, the principal technique for planning and constructing a test or rating instrument. A variable map is also useful for interpreting results. Modest reference is made to the history of mapping leading to its importance in psychometrics. Several maps are given to show the importance and value of mapping a variable by person and item data. The need for a critical appraisal of maps is also stressed.

Maps as Topic↗

The application of phase shifts in NMR for flow measurement.

A brief overview of the history of the application of phase shifts in NMR, and in particular NMR imaging, is presented. The imaging methods include direct phase mapping, Fourier flow imaging (where the flow data are Fourier transformed into one dimension of an image), and alternative methods, where flow-related phase shifts are utilized for flow measurement from the magnitude of the signal. A discussion then follows of the principal errors that can affect the accuracy of the various flow imaging techniques, with particular reference to the phase mapping methods that have been used extensively in our institution. The results from a number of experiments are included to illustrate the extent of the errors and methods of removing or minimizing these effects are suggested.

Blood Circulation↗

Metrics for cortical map organization and lateralization.

Cerebral lateralization refers to the poorly understood fact that some functions are better controlled by one side of the brain than the other (e.g. handedness, language). Of particular concern here are the asymmetries apparent in cortical topographic maps that can be demonstrated electrophysiologically in mirror-image locations of the cerebral cortex. In spite of great interest in issues surrounding cerebral lateralization, methods for measuring the degree of organization and asymmetry in cortical maps are currently quite limited. In this paper, several measures are developed and used to assess the degree of organization, lateralization, and mirror symmetry in topographic map formation. These measures correct for large constant displacements as well as curving of maps. The behavior of the measures is tested on several topographic maps obtained by self-organization of an initially random artificial neural network model of a bihemispheric brain, and the results are compared with subjective assessments made by humans.

Brain Mapping↗