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 559 records · Page 31Linked to original sources

PubMed1995

Confirmation of the 2p locus for the mild autosomal recessive limb-girdle muscular dystrophy gene (LGMD2B) in three families allows refinement of the candidate region.

The mild autosomal recessive limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of muscle diseases. The first gene to be mapped and associated with this phenotype was a locus on 15q based on linkage analysis in families from a French geographic isolate. These results have been confirmed in other populations, but it was shown that there is genetic heterogeneity for this form of LGMD. Recently, a second locus has been mapped to chromosome 2p. The confirmation of the mapping of this second locus in LGMD families from different populations is of utmost importance for the positional cloning of this gene (HGMW-approved symbol LGMD2B). In this publication, haplotypes generated from five chromosome 2 markers from all of the known large families linked to chromosome 2p are reported together with the recombinants that show the current most likely location of the LGMD 2B gene.

Chromosome Mapping↗

PubMed1986

Structure of genes in the cytochrome P-450PBc subfamily: conservation of intron locations in the phenobarbital-inducible family.

The structures of P-450 genes in the rabbit phenobarbital-inducible subfamily of P-450 genes, defined by the cytochrome P-450PBc cDNAs, have been determined by restriction mapping and nucleotide sequencing. A genomic clone corresponding to the 5'-flanking region and the first six exons of the cytochrome P-450PBc2 gene has been examined in detail, and two other clones corresponding to exons 7-9 and the 3'-flanking region of the cytochrome P-450PBc3 and cytochrome P-450(form 1) genes have been characterized less extensively. The intron sequences adjacent to the exons are typical of vertebrate nuclear genes and contain GT and AG at their 5' and 3' ends, respectively. The intron locations in these genes are identical to those in the genes for rat cytochrome P-450b/e, members of the other phenobarbital-inducible subfamily, but completely different from those in the 3-methylcholanthrene-inducible cytochrome P-450 genes. Repetitive sequences are present in at least three introns of the cytochrome P-450PBc2 gene, but not in exons or the 5'-flanking region. The site of transcription initiation for the cytochrome P-450PBc2 gene was determined by primed reverse transcription and S1 mapping. Although the mRNA appeared to be heterogenous at the 5' terminus, the most probable start site is 18 bp downstream from a canonical TATA sequence and 23 bp upstream from the initiator ATG codon. The nucleotide sequence of 800 bp of the 5'-flanking region of the cytochrome P-450PBc2 gene has been determined. This region shares little homology with the 5'-flanking region of rat cytochrome P-450b/e genes, which are 55-60% homologous in the protein-coding region with the members of the P-450PBc subfamily. The amino-terminal sequence of cytochrome P-450PBc2, which could not be determined from the cDNA clones, was derived from the gene sequence. Comparison of the amino-terminal amino acid sequence of P-450PBc2 with those of other mammalian P-450s indicates that the rat isozymes f, g, h, i, and PB1 are in the same subfamily as the rabbit isozymes form 1, form 3b or P-450PBc3, P-450PBc1, and P-450PBc2.

Amino Acid Sequence↗

PubMed1994

Analysis of the yeast NSR1 gene and protein domain comparison between Nsr1 and human hnRNP type A1.

The yeast nucleolar protein-encoding gene NSR1 was isolated by low-stringency screening of a yeast genomic library with the human heterogeneous nuclear ribonucleoprotein type A1 (hnRNP A1) cDNA probe, and was mapped to chromosome VII. RNA abundance was determined and the transcription start point and polyadenylation site were mapped. A comparison between the Nsr1 and hnRNP A1 proteins, based on homopolymer RNA binding to their structural domains in vitro, revealed a striking biochemical similarity. When the N-terminal, lysine- and arginine-rich domain of Nsr1 was removed, the truncated protein behaved similarly to hnRNP A1; furthermore, the two RRM (RNA recognition motif) domains of Nsr1 behaved in the same manner as the two RRM domains of hnRNP A1. The biochemical data, therefore, would support the hypothesis that the two RRM domains in hnRNP A1 and Nsr1 interact with RNA in a similar manner in both mammalian and yeast cells, respectively.

Base Sequence↗

PubMed2002

Non-syndromic autosomal-dominant deafness.

Non-syndromic deafness is a paradigm of genetic heterogeneity. More than 70 loci have been mapped, and 25 of the nuclear genes responsible for non-syndromic deafness have been identified. Autosomal-dominant genes are responsible for about 20% of the cases of hereditary non-syndromic deafness, with 16 different genes identified to date. In the present article we review these 16 genes, their function and their contribution to deafness in different populations. The complexity is underlined by the fact that several of the genes are involved in both dominant and recessive non-syndromic deafness or in both non-syndromic and syndromic deafness. Mutations in eight of the genes have so far been detected in only single dominant deafness families, and their contribution to deafness on a population base might therefore be limited, or is currently unknown. Identification of all genes involved in hereditary hearing loss will help in the understanding of the basic mechanisms underlying normal hearing, will facilitate early diagnosis and intervention and might offer opportunities for rational therapy.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Magnetic resonance image attributes of the bovine ovarian follicle antrum during development and regression.

The magnetic resonance images and maps of bovine ovaries acquired at defined phases of follicular development and regression were studied to determine whether magnetic resonance image attributes of the follicular antrum reflect the physiological status of dominant and subordinate ovarian follicles. Ovariectomies were performed at day 3 of wave one, day 6 of wave one, day 1 of wave two and at >/= day 17 after ovulation. The timings of ovariectomies were selected to acquire growing, early static, late static and regressing follicles of the first wave and preovulatory follicles of the ovulatory wave. Pre-selection and subordinate follicles were also available for analysis. Serum samples were taken on the day of ovariectomy and follicular fluid samples were taken after imaging. Numerical pixel value and pixel heterogeneity in a spot representing approximately 95% of the follicular antrum were quantified in T(1)- and T(2)-weighted images. T(1) and T(2) relaxation rates (T(1) and T(2)), proton density, apparent diffusion coefficients and their heterogeneities were determined from the computed magnetic resonance maps. The antra of early atretic dominant follicles showed higher T(2)-weighted mean pixel value (P < 0.008) and heterogeneity (P < 0. 01) and lower T(2) heterogeneity (P < 0.008) than growing follicles. Subordinate follicles in the presence of a preovulatory dominant follicle had higher T(1), T(1) heterogeneity, proton density, proton density heterogeneity, and lower mean pixel value in T(1)-weighted images than subordinate follicles of the anovulatory wave (P < 0.04). T(1) relaxation rate heterogeneity and proton density heterogeneity were positively correlated with follicular fluid oestradiol concentration (r = 0.4 and 0.3; P < 0.04). T(2) relaxation rate heterogeneity was positively correlated with follicular fluid progesterone concentration (r = 0.4; P < 0.008). Quantitative differences in magnetic resonance image attributes of the antrum observed among phases of follicular development and regression coincided with changes in the ability of the dominant follicle to produce steroid hormones and ovulate, and thus were indicative of physiological status and follicular health.

Animals↗

PubMed2006

Elucidation of the spatial ventricular gradient and its link with dispersion of repolarization.

The ventricular gradient, a notion conceived by Wilson et al during the 1930s, has contributed considerably to a better understanding of the ECG manifestations of the cardiac repolarization process. The power of the ventricular gradient is its ability to assess the primary factors that contribute to the T wave (i.e., heterogeneity of action potential morphology throughout the ventricles) in the presence of secondary factors contributing to the T wave (i.e., heterogeneity in ventricular depolarization instants). Where T-wave morphology is an ECG expression of heterogeneity of the repolarization, the ventricular gradient discriminates between primary or secondary causes of such heterogeneity. Besides the spatial ventricular gradient (Burger's three-dimensional elaboration of Wilson's two-dimensional concept), body surface mapping of local components of the ventricular gradient has emerged as a technique for assessing local ventricular action potential duration heterogeneity. The latter is believed to contribute to localization of arrhythmogenic areas in the heart. The spatial ventricular gradient, which can be computed on the basis of a regular routine ECG and does not require body surface mapping, aims to assess the overall heterogeneity of ventricular action potential morphology. This review addresses the nature and diagnostic potential of the spatial ventricular gradient. The main focus is the role of the spatial ventricular gradient in ECG assessment of dispersion of repolarization, a key factor in arrhythmogeneity.

Electrocardiography↗

PubMed2004

Direct sampling from muscle cross sections for electrophoretic analysis of individual mitochondria.

Muscle is a highly heterogeneous tissue. Practical approaches to sample selectively small regions of muscle cross sections would help to effectively utilize analytical techniques on muscle studies while taking into account tissue heterogeneity. In this report, semimembranosus muscle tissue cross sections were directly sampled and analyzed by capillary electrophoresis (CE) with laser-induced fluorescence detection (LIF). Prior to CE-LIF analysis, a small region in the muscle cross section was stained with 10-nonyl acridine orange (NAO) which is a mitochondrion-selective fluorescent probe known to form a stable complex with cardiolipin, a phospholipid found only in mitochondria. By micromanipulation, the injection end of the capillary was brought into contact with the tissue exhibiting fluorescently labeled mitochondria. Sampling from a region similar in size to the cross section of a single fiber was carried out by applying 11 kPa of negative pressure for 3 s. When an electric field of -200V/cm was applied, fluorescently labeled mitochondria electromigrated and were individually detected by postcolumn LIF detection. For each sample, the electropherogram displays a migration time window with a collection of narrow peaks. The collection of individual peak measurements is represented as a distribution of individual intensities related to cardiolipin content of mitochondria and a distribution of individual electrophoretic mobilities. Positioning the capillary injection end was sufficiently spatially accurate to deplete mitochondria in the sampled region upon repetitive injections. Treatment of a muscle cross section with a protease (trypsin) prior to mitochondria sampling resulted in a higher number of detected mitochondria, suggesting that one of the effects of this enzyme is a partial digestion of the muscles myofibrils, which eases the release of interfibrillar mitochondria entangled within these fibers. The protease treatment also resulted in changes to the electrophoretic mobility distribution of individual mitochondria, which may imply that partial digestion of proteins bound to the mitochondria contributes to the alteration in the electrophoretic mobility of mitochondria. The ability to sample a region as small as a single muscle fiber cross section and its direct CE-LIF analysis opens exciting possibilities for the direct analysis of muscle biopsies and mapping the mitochondrial electrophoretic properties in highly heterogeneous tissues.

Aminoacridines↗

PubMed1974

Murine type-C virus group-specific antigens: interstrain immunochemical, biophysical, and amino acid sequence differences.

The 30,000-molecular-weight internal protein, p30, was purified from seven strains of mouse type-C viruses. The individual p30's showed variation in isoelectric points and also intrastrain heterogeneity. The individual p30's could be distinguished by peptide map and quantitative complement fixation techniques with relatedness estimates of >95%. Amino terminal sequence analysis showed variability at position 4 for several p30's with complete homology otherwise through 24 residues. The intrastrain heterogeneity in p30 isoelectric points could not be explained by common contaminants, as shown by peptide mapping, and is more likely based on post-transcriptional modifications. These data provide a chemical basis for the recently described type-specific immunological properties of individual p30's.

Amino Acid Sequence↗

PubMed1990

Possible genetic heterogeneity in X linked hypohidrotic ectodermal dysplasia.

Hypohidrotic ectodermal dysplasia has been mapped to Xq11-q13 by linkage studies and by a translocation in a manifesting female. We report a family with hypohidrotic ectodermal dysplasia in which the disease did not segregate with this region of the X chromosome as expected. Ten DNA probes which are localised between Xp11 and Xq22 were used in the investigation. The difficulties in diagnosing the carrier state in this condition and the possibility of non-allelic heterogeneity are discussed.

Chromosome Mapping↗

PubMed2004

Characteristics of recurrence in patients who underwent lymphatic mapping for vulvar cancer.

OBJECTIVE: To evaluate patients with vulvar cancer who experienced a recurrence after undergoing lymphatic mapping and sentinel lymph node (SLN) biopsy. METHODS: We reviewed the records of 52 patients who underwent vulvectomy and lymphatic mapping with blue dye for treatment of vulvar cancer at our institution from 1993 to 1999 and identified patients who experienced recurrent disease. RESULTS: Fourteen (27%) of 52 patients experienced a recurrence. The patients' median age was 60 years (range 35-84 years). Nine patients had squamous lesions, four patients had melanoma, and one patient had Paget's disease with stromal invasion. Four tumors were stage T1, seven were T2, and three were T3. Eight lesions were located at the midline and six were lateral. Thirteen patients underwent superficial inguinal lymphadenectomy while one patient underwent SLN biopsy only. Postoperatively, seven patients underwent no further treatment, six underwent radiation therapy, and one patient underwent chemotherapy. The median follow-up was 46 months and the median disease-free interval was 21 months. Primary recurrence was in the vulva in eight patients (57%), in the groin in three patients (21%), and distant in three patients (21%). Nine of 32 (22%) squamous lesions recurred, four (57%) of seven melanomas recurred, and the sole patient with invasive Paget's recurred. Patient weight was found to be significantly different between patients who experienced a recurrence and those who did not (P = 0.05). At least one SLN was identified in 46 (88%) of the 52 patients. One (17%) of six patients in whom no SLN was identified experienced a recurrence, and 13 (28%) of 46 patients in whom a SLN was identified experienced a recurrence (P = 0.5). In the 41 patients with negative SLNs and negative non-SLNs, the recurrence rate was 24%; in the six patients with positive SLNs and negative non-SLNs, the recurrence rate was 40%; and in the five patients with positive SLNs and positive non-SLNs, the recurrence rate was 40% (P = 0.6). No patients had a negative SLN and positive non-SLN. Of the three patients who experienced a recurrence in the groin, one had a negative SLN and negative non-SLN, one had a positive SLN and positive non-SLN, and one had no SLN identified and a negative non-SLN. CONCLUSIONS: . This heterogeneous group of patients who underwent lymphatic mapping with blue dye had similar patterns of recurrence to reported series of patients who did not undergo lymphatic mapping. Groin relapse following a negative SLN biopsy is of concern and suggests that long-term follow-up data are required before lymphatic mapping and SLN biopsy alone can be considered standard treatment for patients with vulvar cancer.

Adult↗

PubMed2002

Novel locus for autosomal dominant pure hereditary spastic paraplegia (SPG19) maps to chromosome 9q33-q34.

Hereditary spastic paraplegia is a clinically and genetically heterogeneous disorder characterized by progressive spasticity of the lower limbs. Seven loci for autosomal dominant pure hereditary spastic paraplegia (ADPHSP) have already been mapped on chromosomes 14q, 2p, 15q, 8p, 12q, 19q, and 2q. We report on an Italian family affected by ADPHSP for which we excluded linkage with the known loci and performed a genome-wide search. Linkage analysis and haplotype construction permitted the identification of a novel ADPHSP locus on the long arm of chromosome 9, designated SPG19. The phenotype was characterized by late onset (range, 36-55 years) and mild disability, with only 1 patient bound to a wheelchair after 31 years of disease. Urinary disturbances (urgency and/or incontinence) were always present, even in young patients with a short disease history.

Adolescent↗

PubMed1998

Linkage of a commoner form of recessive amyotrophic lateral sclerosis to chromosome 15q15-q22 markers.

Autosomal recessive familial amyotrophic lateral sclerosis (RFALS) is a rare form of ALS that usually presents at an early age with slow progression of symptoms. RFALS is clinically and genetically heterogeneous and the locus of RFALS type 3 was mapped to 2q33 (ALS2) in a single family. We now report linkage of a more-common form of RFALS to chromosome 15q15-q22 markers (ALS5) and show further genetic locus heterogeneity in RFALS. ALS5 is the locus for most families with RFALS and appears to be present in both North African and European populations.

Age of Onset↗

PubMed1999

Flow and oxygenation dependent (FLOOD) contrast MR imaging to monitor the response of rat tumors to carbogen breathing.

Gradient recalled echo (GRE) images are sensitive to both paramagnetic deoxyhaemoglobin concentration (via T2*) and flow (via T1*). Large GRE signal intensity increases have been observed in subcutaneous tumors during carbogen (5% carbon dioxide, 95% oxygen) breathing. We term this combined effect flow and oxygenation-dependent (FLOOD) contrast. We have now used both spin echo (SE) and GRE images to evaluate how changes in relaxation times and flow contribute to image intensity contrast changes. T1-weighted images, with and without outer slice suppression, and calculated T2, T2* and "flow" maps, were obtained for subcutaneous GH3 prolactinomas in rats during air and carbogen breathing. T1-weighted images showed bright features that increased in size, intensity and number with carbogen breathing. H&E stained histological sections confirmed them to be large blood vessels. Apparent T1 and T2 images were fairly homogeneous with average relaxation times of 850 ms and 37 ms, respectively, during air breathing, with increases of 2% for T1 and 11% for T2 during carbogen breathing. The apparent T2* over all tumors was very heterogeneous, with values between 9 and 23 ms and localized increases of up to 75% during carbogen breathing. Synthesised "flow" maps also showed heterogeneity, and regions of maximum increase in flow did not always coincide with maximum increases in T2*. Carbogen breathing caused a threefold increase in arterial rat blood PaO2, and typically a 50% increase in tumor blood volume as measured by 51Cr-labelled RBC uptake. The T2* increase is therefore due to a decrease in blood deoxyhaemoglobin concentration with the magnitude of the FLOOD response being determined by the vascular density and responsiveness to blood flow modifiers. FLOOD contrast may therefore be of value in assessing the magnitude and heterogeneity of response of individual tumors to blood flow modifiers for both chemotherapy, antiangiogenesis therapy in particular, and radiotherapy.

Animals↗

PubMed1993

North Carolina macular dystrophy (MCDR1). A review and refined mapping to 6q14-q16.2.

The macular degenerations comprise a heterogeneous group of diseases, generally reported in small families. Single, large family studies of North Carolina macular dystrophy have aided in defining the spectrum of the phenotype of this disorder and its relationship to other macular degenerations. North Carolina macular dystrophy has many phenotypic similarities to age-related macular degeneration with the glaring exception of the early age of onset of North Carolina macular dystrophy. The authors initially reported mapping this disease by linkage to the long arm of chromosome 6. They now report additional data on a total of 247 individuals in the original North Carolina macular dystrophy family whom we ascertained for clinical and molecular genetic studies. Standard clinical ophthalmic examination revealed that 96 of these individuals were affected. Molecular genetic studies increased the LOD score to 23 and refined the genomic localization of the disease-causing gene to 6q14-q16.2.

Adult↗

PubMed2003

Comparison of minisatellites.

In the class of repeated sequences that occur in DNA, minisatellites have been found polymorphic and became useful tools in genetic mapping and forensic studies. They consist of a heterogeneous tandem array of a short repeat unit. The slightly different units along the array are called variants. Minisatellites evolve mainly through tandem duplications and tandem deletions of variants. Jeffreys et al. (1997) devised a method to obtain the sequence of variants along the array in a digital code and called such sequences maps. Minisatellite maps give access to the detail of mutation processes at work on such loci. In this paper, we design an algorithm to compare two maps under an evolutionary model that includes deletion, insertion, mutation, tandem duplication, and tandem deletion of a variant. Our method computes an optimal alignment in reasonable time; and the alignment score, i.e., the weighted sum of its elementary operations, is a distance metric between maps. The main difficulty is that the optimal sequence of operations depends on the order in which they are applied to the map. Taking the maps of the minisatellite MSY1 of 609 men, we computed all pairwise distances and reconstructed an evolutionary tree of these individuals. MSY1 (DYF155S1) is a hypervariable locus on the Y chromosome. In our tree, the populations of some haplogroups are monophyletic, showing that one can decipher a microevolutionary signal using minisatellite maps comparison.

Algorithms↗

PubMed1992

High density molecular linkage maps of the tomato and potato genomes.

High density molecular linkage maps, comprised of more than 1000 markers with an average spacing between markers of approximately 1.2 cM (ca. 900 kb), have been constructed for the tomato and potato genomes. As the two maps are based on a common set of probes, it was possible to determine, with a high degree of precision, the breakpoints corresponding to 5 chromosomal inversions that differentiate the tomato and potato genomes. All of the inversions appear to have resulted from single breakpoints at or near the centromeres of the affected chromosomes, the result being the inversion of entire chromosome arms. While the crossing over rate among chromosomes appears to be uniformly distributed with respect to chromosome size, there is tremendous heterogeneity of crossing over within chromosomes. Regions of the map corresponding to centromeres and centromeric heterochromatin, and in some instances telomeres, experience up to 10-fold less recombination than other areas of the genome. Overall, 28% of the mapped loci reside in areas of putatively suppressed recombination. This includes loci corresponding to both random, single copy genomic clones and transcribed genes (detected with cDNA probes). The extreme heterogeneity of crossing over within chromosomes has both practical and evolutionary implications. Currently tomato and potato are among the most thoroughly mapped eukaryotic species and the availability of high density molecular linkage maps should facilitate chromosome walking, quantitative trait mapping, marker-assisted breeding and evolutionary studies in these two important and well studied crop species.

Centromere↗

PubMed1982

Structural organization of rat ribosomal genes restriction endonuclease analysis of genomic and cloned ribosomal DNAs.

Structural organization of the rat ribosomal repeating unit was studied using hybridization of blotted restriction fragments of total rat DNA with alpha-32P-labeled cDNA probe synthesized on the 18S and 28S rRNAs. A detailed restriction endonuclease map was constructed, the 18S and 28S rRNA genes mapped and the sizes of the rat ribosomal repeating units determined. Considerable site heterogeneity of rat rDNA was revealed in both nontranscribed and external transcribed spacers. Recombinant phages containing the whole set of transcribed regions and a considerable part of a nontranscribed spacer of the rDNA were selected from the rat gene library. The restriction maps of the cloned rDNA fragments are in good agreement with the map constructed by Southern's technique, add to this map and support the existence of site heterogeneity in ribosomal repeating units. Proximal to the 3'-end of the 28S rRNA gene an internally repetitive region was found, each repeating unit being equal to approx. 150 bp. The site for transcription initiation was mapped 4.0-4.5 kb upstream from the 5'-end of the 18S rRNA gene. Frequently reiterated interspersed sequences were found in the nontranscribed spacer at approx. 2-3 kb distance from both ends of the transcribed region.

Animals↗

PubMed1998

Genetics of complex human diseases: genome screening, association studies and fine mapping.

Positional cloning has been applied successfully to many Mendelian disorders. Because of the public health significance, there is strong interest in mapping susceptibility genes for common disorders, such as asthma and allergy, that have a genetic component. Genome-wide screening has been very useful in detecting regions of the genome likely to contain susceptibility genes. There are multiple chromosomal regions implicated in asthma and now the difficult process of finding the genes and relevant mutations is underway. Two approaches that are being utilized are those of association studies in candidate genes, and haplotype sharing or identical by descent (IBD) mapping. Although these are useful approaches, it is important to realize the strengths and limitations of each. The level of significance needed for an initial study or a replication study should be considered in light of the prior evidence for studying a specific gene polymorphism. Haplotype-sharing approaches, although difficult to use in outbred heterogeneous populations, may provide important insight into fine mapping and gene localization.

Asthma↗