PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Heterogeneity Mapping”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 181 records · Page 10Linked to original sources
PubMed1992

Immunohistochemical detection of estrogen receptors on paraffin sections of normal, hyperplatic and carcinomatous endometrium.

The present study is the first dealing with the demonstration of estrogen receptors (ER) in up to 8-year-old paraffin blocks of endometrial curettage samples routinely fixed in 10% formalin. The Mab ER-ICA was used in a modified peroxidase-antiperoxidase method after pretreatment of paraffin sections with pronase. Eleven cases with proliferative, 11 cases with secretory endometrium, 20 cases with adenocystic, 21 with adenomatous hyperplasia and 27 endometrial adenocarcinomas were tested. The two main parameters, namely the percentage of ER-positive cells and the intensity of the immunostaining, were higher in the proliferative phase followed in a declining sequence by adenocystic hyperplasia, adenomatous hyperplasia, adenocarcinomas and the secretory phase of endometrium. Interestingly, the intensity of the immunostaining showed a positive relationship to the percentage of ER-positive cells (r = 0.93, p less than 0.001). It seems that the immunohistochemical demonstration of ER in paraffin sections of uterine specimens is an easy and reliable method for the mapping of the heterogeneous expression of ER and their comparative study with the well preserved histopathological features even in old archival paraffin-embedded material.

Adenocarcinoma↗
PubMed1999

Analysis of 6 short tandem repeat loci in Navarre (northern Spain).

A genetic study was performed on a sample of 146 autochthonous individuals from the province of Navarre (northern Spain) to test for 6 STR systems: CSF1PO, TPOX, TH01, F13A1, FES/FPS, and VWA31/A. The Navarre population has a series of allele frequencies that are at the extreme end of the European range of variation and that are in most cases similar to those found in the Basque population of the provinces of Alava, Biscay, and Guipuzcoa. This similarity is corroborated by correspondence analysis, in which the population of Navarre is at one end of the first axis with the Basque sample close to it and the remaining European populations far removed. In tree-type representations the Navarre population is grouped with the Basque series at 1 end. Even so, the comparison of allele frequency distributions by the chi-square heterogeneity test indicates that these 2 groups are statistically different. Our results together with the cultural relationship that exists between all the Basque-speaking provinces and the genetic heterogeneity described in earlier studies between the Basque provinces of Alava, Biscay, and Guipuzcoa (Aguirre et al. 1989; Manzano, Orue et al. 1996; Manzano, Aguirre et al. 1996) lead us to believe that the Navarre population lies within the heterogeneous Basque genetic map.

Chi-Square Distribution↗
PubMed2002

A ratiometric imaging method for mapping ion flux densities.

A heterogeneous distribution of ion channels on the cell surface is a prerequisite for several cellular functions. Thus, there has been considerable interest in methods allowing the mapping of ion channel distributions. Here we report on a novel ratiometric imaging technique appropriate to measure spatially resolved ion flux signals by using ion sensitive dyes. However, given that certain relevant cell properties like the surface to volume ratio may exhibit significant spatial heterogeneities, the local influx signal cannot be interpreted as a measure of the local open channel concentration or flux density. To overcome this problem, we suggest an internal normalization procedure, which, in analogy to, but clearly distinct from, well-established ratioing techniques, eliminates effects which would otherwise obscure the desired result. Ratioing is performed on flux signals from a given cell, triggered by two different, subsequent stimuli. If the two stimuli address different ion channels, the flux density distribution caused by two channel types can be determined relative to each other. In cases where one of the stimuli triggers a spatially homogeneous flux signal, ratioing yields an ion flux density map for a given channel type. Thus distribution patterns of ion channels active during a given stimulus may be derived.

Animals↗
PubMed2003

Genetic heterogeneity in inherited spastic paraplegia associated with epilepsy.

We have recently mapped a new rare form of spastic paraplegia complicated by bilateral cataracts, gastroesophageal reflux with persistent vomiting, and amyotrophy to chromosome 10q23.3-q24.2. This locus, named SPG9, is located in an interval spanning about 12 cM of genomic DNA, between markers D10S536 and D10S603, where different neurological disorders have been mapped. In particular, a gene for partial epilepsy has been assigned to a 3 cM interval between markers D10S185 and D10S577, which is completely included in the SPG9 critical region. A few families affected with spastic paraplegia and epilepsy have been reported; in the present study, we tested a pedigree with concurrence of spastic paraplegia, epilepsy, and mental retardation inherited as an autosomal dominant trait, using markers located in the SPG9 interval. Haplotype reconstruction excluded the linkage to 10q23.3-q24.2. In addition, the seven different loci so far reported to be associated with autosomal dominant pure forms of spastic paraplegia have been tested and excluded by linkage analysis and haplotype reconstruction, including SPG4 on chromosome 2p22-p21, where a familial form of spastic paraplegia associated with dementia and epilepsy has been mapped. These data confirm genetic heterogeneity in familial spastic paraplegia with epilepsy and suggest a specific locus for the family here analyzed.

DNA↗
PubMed1996

A novel splice-site mutation in the gamma subunit of the epithelial sodium channel gene in three pseudohypoaldosteronism type 1 families.

Pseudohypoaldosteronism type 1 (PHA1, OMIM 264350) is an uncommon inherited disorder characterized by salt-wasting and end-organ unresponsiveness to mineralocorticoids. A complete genome search using homozygosity mapping in eleven consanguineous families with PHA1 provided conclusive evidence of linkage with heterogeneity. The disease locus mapped to chromosome 16p12.2-13.11 in six families and to 12p13.1-pter in the other five families. These two chromosomal regions harbour the genes encoding the three subunits of the human amiloride sensitive epithelial sodium channel (hENaC): SCNN1B and SCNN1G on 16p and SCNN1A on 12p. Our linkage results have been further supported by the recent report of mutations in the alpha and beta subunit genes in PHA1 patients. We now report the identification of a 3' splice site mutation in SCNN1G (318-1 G-->A) in three families showing linkage to 16p. Abnormal splicing results with the production of two messenger RNAs, one arising from activation of an adjacent cryptic splice site and the other from skipping of the downstream exon. The two corresponding mutant gamma hENaC subunits are predicted to have three highly conserved amino acids in the extracellular domain replaced by a novel amino acid (KYS106-108-->N) and truncation from 649 to 134 amino acids respectively. These three families all originate from the Indian sub-continent and the probands have severe generalized PHA. They share a common haplotype which suggests the presence of a founder mutation in this sub-population.

Amino Acid Sequence↗
PubMed2004

Finding prostate cancer susceptibility genes.

Prostate cancer is a heterogeneous disease with multiple loci contributing to susceptibility. Traditionally, genome-wide scans using high-risk families have utilized stratification by number of affected individuals, family history of other cancers, or family age at diagnosis to improve genetic homogeneity. In addition to locus heterogeneity, for later onset diseases such as prostate cancer, a major limitation to mapping efforts is that key parental DNA samples are rarely available. The lack of available samples from upper generations reduces inheritance information, and as a result, the standard 10-cM genome scan does not provide full power to detect linkage. To increase the ability to find disease-associated loci, much denser genome-wide scans must be undertaken in multiple ethnic groups. In addition, new ways of defining homogenous subsets of families need to be developed.

Chromosome Mapping↗
PubMed2005

Identification of a novel locus for Marie Unna hereditary hypotrichosis to a 17.5 cM interval at 1p21.1-1q21.3.

Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant disorder characterized by coarse, wiry, twisted hair developed in early childhood and followed by the development of alopecia. A locus for this disorder was localized to chromosome 8p, but no gene responsible for it has been identified. To map and determine whether MUHH is a genetically heterogeneous disorder and identify the disease gene locus in a four-generation Chinese family with MUHH. We performed a genome-wide scan in this family. Two-point linkage analysis was performed using Linkage programs version 5.10 software and haplotype was constructed with Cyrillic Version 2.02 software. We failed to confirm the previous locus for MUHH at chromosome 8p and obtained the conformed evidence for linkage at chromosome 1. Two-point logarithm of odds ratio scores > or =3 were observed at markers D1S2746 and D1S2881. Haplotype analysis localized this locus to a 42 Mb region. The previous results and this study have shown that MUHH is a genetically heterogeneous disorder. Our family was mapped to a 17.5 cM region between markers D1S248 and D1S2345.

Adult↗
PubMed2002

A rule driven bi-directional translation system for remapping queries and result sets between a mediated schema and heterogeneous data sources.

As the number of online biomedical data sources increases, so too do the number of ways to access such data. The research described herein focuses on creating a data access system that provides bi-directional translation and mapping of data between heterogeneous databases and a mediated schema. Semantic mapping rules stored in a knowledge base are used by our generalized software to convert XML query results obtained from each data source to a common schema representing a single ontology. We apply this approach to the domain of online genetic databases, demonstrating the system's scalability and integratability.

Databases as Topic↗
PubMed1975

Heterogeneity of mitochondrial DNA from Saccharomyces carlsbergensis. Denaturation mapping by electron microscopy.

Electronmicroscopic observation of the denaturation pattern of 130 partially denaturated linear mitochondrial DNA molecules from Saccharomyces carlsbergensis was used to investigate the distribution of AT-rich sequences within the mitochondrial genome. The molecules were observed after heating to 43 degrees C in the presence of 12% formaldehyde. These conditions resulted in an average denaturation per molecule of 21%. The average length of the molecules was 10 mum, and a few molecules had a length corresponding to the size of the complete genome. The undenaturated regions varied in length from 0.1 to 5.0 mum with denaturated regions of length 0.02 to 0.1 mum in between. A denaturation map was constructed by use of one of the long molecules (28.7 mum) as a master molecule for positioning of all other molecules. This map shows distinct regions corresponding to the position of easily denaturated sequences in the mitochondrial DNA. These sequences which presumably correspond to the very AT-rich regions, known to exist in the yeast mitochondrial DNA, were found at intervals of about 0.5 - 3 mum on the map.

Base Sequence↗
PubMed2006

Genome-wide genetic association of complex traits in heterogeneous stock mice.

Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits.

Animals↗
PubMed2005

Discrepancies in upper and lower limb patterning in split hand foot malformation.

Discrepancies in upper and lower limb patterning in split hand foot malformation. Split hand foot malformation (SHFM) is genetically heterogeneous with five loci mapped to date. Highly variable in presentation, it can occur as an isolated finding or with other anomalies. The genetic heterogeneity and clinical variability make genetic counselling of SHFM families challenging. By establishing genotype/phenotype correlations, one can provide insight into responsible developmental genes and help to direct mapping efforts and target genetic testing, ultimately providing more accurate information for family members. Preaxial involvement of the upper extremities was a significant discriminating limb-specific variable in our analysis of genetically mapped SHFM cases. This finding, which was originally identified through descriptive epidemiology, was subsequently confirmed by discriminant function analysis (p < 0.0001) to be a significant locus discriminator. Preaxial involvement of the upper extremities was most commonly seen at the SHFM3 locus mapped to chromosome 10q24 (OMIM 600095) and consisted of proximally placed thumbs and/or triphalangeal thumbs (TPT), preaxial polydactyly and/or absence of the first ray. These patients' feet, however, tended to show a classical central longitudinal deficiency without a significant preaxial component. This article discusses this discrepant clefting pattern between the upper and lower extremities and proposes potential mechanisms.

Abnormalities, Multiple↗
PubMed1995

Management of evolving map data: data structures and algorithms based on the framework map.

A consensus framework map of a chromosome is the single most useful map of the chromosome, because of the amount of information it holds as well as the quality of the supporting data backing the putative order of its objects. We describe data structures and algorithms to assist in framework map maintenance and to answer queries about order and distance on genomic objects. We show how these algorithms are efficiently implemented in a client-server relational database. We believe that our data structures are particularly suitable for databases to support collaborative mapping efforts that use heterogeneous methodologies. We summarize two applications that use these algorithms: CHROMINFO, a database specifically designed for framework map maintenance; and the shared client-server database for the chromosome 12 genome center.

Algorithms↗
PubMed2002

High-resolution mapping of tachycardia originating from the superior vena cava: evidence of electrical heterogeneity, slow conduction, and possible circus movement reentry.

Superior Vena Cava Reentry. High-resolution mapping of a tachycardia originating from the superior vena cava (SVC) in a patient with atrial fibrillation is described. Unidirectional circuitous repetitive activation encompassing the full tachycardia cycle length was documented around a line of block within the myocardial sleeve of the SVC. Intermittent conduction to the right atrium resulted in an irregular atrial tachycardia. Evidence of electrical heterogeneity and slow conduction persisted in sinus rhythm and was exaggerated by premature stimulation but did not reproduce the activation pattern during tachycardia. All the available evidence is best compatible with circus movement reentry within the SVC, with marked slow and anisotropic conduction responsible for the restricted dimensions of the reentrant circuit. These findings may suggest a similar substrate and arrhythmia mechanism in the myocardium of the pulmonary veins.

Atrial Fibrillation↗
PubMed1989

Linkage heterogeneity between X-linked retinitis pigmentosa and a map of 10 RFLP loci.

In nine families in which X-linked retinitis pigmentosa (XLRP) is segregating, the lod scores of XLRP in a map of 10 RFLP loci were obtained by multipoint linkage analysis. The XLRP locus was located telomeric to DXS7 in seven of the families and centromeric to DXS7 in two of the families. Under the hypothesis of two XLRP loci, a heterogeneity (admixture) test was performed, providing significant evidence of heterogeneity in XLRP (P less than .01). No correlation was detected between the clinical manifestations of XLRP and the two different disease loci.

Chromosome Mapping↗
PubMed1997

Identification of N(G)-methylarginine residues in human heterogeneous RNP protein A1: Phe/Gly-Gly-Gly-Arg-Gly-Gly-Gly/Phe is a preferred recognition motif.

Three sites of N(G),N(G)-arginine methylation have been located at residues 205, 217, and 224 in the glycine-rich, COOH-terminal one-third of the HeLa A1 heterogeneous ribonucleoprotein. Together with the previously determined dimethylated arginine at position 193 [Williams et al., (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 5666-5670], it is evident that all four sites fall within a span of sequence between residues 190 and 233 that contains multiple Arg-Gly-(Gly) sequences interspersed with phenylalanine residues. These RGG boxes have been postulated to represent an RNA binding motif [Kiledjian and Dreyfuss (1992) EMBO J. 11, 2655-2664]. Dimethylation of HeLa A1 appears to be quantitative at each of the four positions. Arginines 205 and 224 have been methylated in vitro by a nuclear protein arginine methyltransferase using recombinant (unmethylated) A1 as substrate. This suggests A1 may be an in vivo substrate for this enzyme. Examination of sequences surrounding the sites of methylation in A1 along with a compilation from the literature of sites that have been identified in other nuclear RNA binding proteins suggests a methylase-preferred recognition sequence of Phe/Gly-Gly-Gly-Arg-Gly-Gly-Gly/Phe, with the COOH-terminal flanking glycine being obligatory. Taken together with data in the literature, identification of the sites of A1 arginine methylation strongly suggests a role for this modification in modulating the interaction of A1 with nucleic acids.

Amino Acid Sequence↗
PubMed1986

The binding of MAP-2 and tau on brain microtubules in vitro: implications for microtubule structure.

We have presented data that indicate that MAP-2 associates with brain microtubules at nonrandomly distributed sites, whose distribution on the microtubule polymer can best be described by the 12-dimer MAP superlattice originally described by Amos; because of the additional spacings, however, between MAP-2 projections observed on MAP-2-saturated microtubules, we suggest that the 6-dimer MAP superlattice, or what we will call the double Amos superlattice, more completely specifies the total set of MAP-binding sites on cytoplasmic microtubules. Second, we have shown that brain microtubules reassembled in vitro contain a heterogeneous population of MAP-binding sites, which differ in their affinities for the two MAPs, MAP-2 and tau. Third, we have shown that microtubule populations that differ in their MAP content have subtle, but detectable differences in their tubulin isotype composition. Based on all the data presented here, we have presented the idea of a nonrandom distribution of tubulin isotypes within a microtubule as a means by which a cell could specify both the identity and the distribution of MAP-binding sites.

Animals↗