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 487 records · Page 27Linked to original sources

PubMed1992

Mapping of the formin gene and exclusion as a candidate gene for the autosomal recessive form of limb-girdle muscular dystrophy.

Limb-Girdle Muscular Dystrophy (LGMD) is a myopathy with clinical and transmission heterogeneity. The recessive form, LGMD2, has been recently mapped by linkage analysis to 15q. As an attempt to identify the gene involved in this pathology, we tested as candidate gene the LD locus, called LD for limb deformity. This gene has recently been identified and mapped to chromosome 15q13-q14. It is homologous to the murine formin gene which is localized to mouse chromosome 2. Mutations in this murine gene have been shown to cause limb deformity and kidney defect. YAC clones containing the LD gene were isolated and utilised to confirm the cytogenetic localisation. Internal DNA polymorphisms of the LD locus were analyzed in LGMD2 and CEPH families. The LD gene was mapped between the alpha cardiac actin gene and the D15S24 locus. Crossovers between the LGMD2 and the LD loci excluded the LD gene as a candidate for LGMD2.

Base Sequence↗

PubMed2005

A novel autosomal recessive non-syndromic hearing impairment locus (DFNB47) maps to chromosome 2p25.1-p24.3.

Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. Autosomal recessive (AR) forms of prelingual HI account for approximately 75% of cases with a genetic etiology. A novel AR non-syndromic HI locus (DFNB47) was mapped to chromosome 2p25.1-p24.3, in two distantly related Pakistani kindreds. Genome scan and fine mapping were carried out using microsatellite markers. Multipoint linkage analysis resulted in a maximum LOD score of 4.7 at markers D2S1400 and D2S262. The three-unit support interval was bounded by D2S330 and D2S131. The region of homozygosity was found within the three-unit support interval and flanked by markers D2S2952 and D2S131, which corresponds to 13.2 cM according to the Rutgers combined linkage-physical map. This region contains 5.3 Mb according to the sequence-based physical map. Three candidate genes, KCNF1, ID2 and ATP6V1C2 were sequenced, and were found to be negative for functional sequence variants.

Chromosome Mapping↗

PubMed2001

Prior mapping for nonlinear flows in random environments.

We analyze nonlinear flows in randomly heterogeneous environments, which are characterized by state-dependent diffusion coefficients with spatially correlated structures. The prior Kirchhoff mapping is used to describe such systems by linear stochastic partial differential equations with multiplicative noise. These are solved through moment equations which are closed, alternatively, either by perturbation expansions, or by a posterior linear mapping closure. The latter relies on the assumption that the state variable is a spatially distributed Gaussian field. We demonstrate that the former approach is more robust.

Journal Article↗

PubMed1998

Physical and genetic map of the obligate intracellular bacterium Coxiella burnetii.

Pulsed-field gel electrophoresis and PCR techniques have been used to construct a NotI macrorestriction map of the obligate intracellular bacterium Coxiella burnetii Nine Mile. The size of the chromosome has been determined to be 2,103 kb comprising 29 NotI restriction fragments. The average resolution is 72.5 kb, or about 3. 5% of the genome. Experimental data support the presence of a linear chromosome. Published genes were localized on the physical map by Southern hybridization. One gene, recognized as transposable element, was found to be present in at least nine sites evenly distributed over the whole chromosome. There is only one copy of a 16S rRNA gene. The putative oriC has been located on a 27.5-kb NotI fragment. Gene organization upstream the oriC is almost identical to that of Pseudomonas putida and Bacillus subtilis, whereas gene organization downstream the oriC seems to be unique among bacteria. The physical map will be helpful in investigations of the great heterogeneity in restriction fragment length polymorphism patterns of different isolates and the great variation in genome size. The genetic map will help to determine whether gene order in different isolates is conserved.

Bacillus subtilis↗

PubMed2000

Mapping of the autosomal recessive (AR) craniometaphyseal dysplasia locus to chromosome region 6q21-22 and confirmation of genetic heterogeneity for mild AR spondylocostal dysplasia.

We report on a four-generation inbred family including 10 individuals affected with a form of craniotubular dysplasia (CTD). All affected patients were born to consanguineous healthy parents; this finding, together with the equal sex ratio among affected individuals and the occurrence of only normal individuals among their offspring, indicates that the disease in this family is an autosomal recessive (AR) trait. Taking into account the segregation pattern of the disease in the family and the radiological characteristics of two young CTD patients, the most likely diagnosis for the defect is AR craniometaphyseal dysplasia (CMD). CMD is a CTD, with both autosomal dominant (AD) and recessive forms. The description of the present genealogy confirms the AR pattern of inheritance of some cases of CMD and contributes to a better delineation of the clinical spectrum of AR CMD, suggesting a more pronounced diaphyseal involvement in the AR compared with the AD CMD. Through genomewide scanning, we mapped the AR CMD to a 7 cM interval, between D6S302 and D6S1639, at 6q21-22 region. We have also excluded the positional candidate COL10A1 gene as being the responsible for this disorder. Curiously, a form of AR spondylocostal dysplasia (SD) also segregates in the family, including one affected individual with both conditions. The gene DLL3, mapped to 19q13 region, was recently found to be responsible for one form of AR SD; however, we did not find evidence of linkage between this 19q region and the SD segregating in our family, thus implying in genetic heterogeneity for AR SD.

Adult↗

PubMed1983

In vivo transcription of a eukaryotic regulatory gene.

The PPR1 gene encodes the positive regulator of the URA1 and URA3 genes in yeast. Its transcription product is a 2.9-kb polyadenylated RNA with an extremely short half-life of 1 min. The induced or non-induced cell contains approximately 0.1 molecules of PPR1 RNA, a constitutive level which is not altered by changing the number of structural genes to be regulated. The DNA sequence of a 399-bp AccI-Bg/II fragment including 180 nucleotides of the 5'-flanking region of the gene PPR1 has been determined. By S1 mapping we present evidence that the 5' non-coding region of the PPR1 mRNA is heterogeneous in length. The 5' termini of the different RNAs map 20, 36, 45 and 50 nucleotides upstream from the translation start codon. The sequence indicates that the only open translation phase begins with an AUG codon that is preceded by two out-of-frame AUG triplets. This particular structure of the 5'-terminal sequence of the transcripts of PPR1 is discussed in relation to both their stability and translational efficiency.

Base Composition↗

PubMed1993

Correlation between [3H]thymidine and proliferating cell nuclear antigen (PCNA)/cyclin indices in archival, formaldehyde-fixed human colorectal tissues.

Sections were obtained from archival colorectal tissue samples preserved in paraffin since 1974, after an in vitro incubation with [3H]thymidine and fixation in formaldehyde. These sections were submitted to immunohistochemical staining with the 19A2 monoclonal antibody against proliferating cell nuclear antigen (PCNA) (i.e. the PCNA identified as the auxiliary protein to DNA polymerase delta), followed by autoradiography. Analysis of this double-labelled material revealed an excess of PCNA-labelled over 3H-labelled nuclei, as expected from our previous studies with this fixative. On the other hand, PCNA positive nuclei showed the same overall topographical distribution as the [3H]thymidine-labelled ones, eventually revealing the same heterogeneity or abnormality in the spatial distribution of proliferative cells. Finally, there was a highly significant correlation (r = 0.898; P < 0.0001) between the [3H]thymidine labelling index (TLI) and the proportion of PCNA-positive nuclei (PCNAF-LI). PCNA immunostaining after formaldehyde fixation thus appears as a valid approach for mapping the proliferative compartment and demonstrating tumour heterogeneity or abnormalities in the distribution of proliferative cells. The excellent correlation between the PCNAF-LI and the TLI also makes PCNA immunostaining a simple tool for retrospective or prospective studies on pathological material aimed at evaluating the potential relevance of proliferative indices to clinical prognosis or prediction of cancer risk.

Adenocarcinoma↗

PubMed1994

Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11.

Autosomal dominant ataxias are a genetically heterogeneous group of disorders for which spinocerebellar ataxia (SCA) loci on chromosomes 6p, 12q, 14q and 16q have been reported. We have examined 170 individuals (56 of whom were affected) from a previously unreported ten-generation kindred with a dominant ataxia that is clinically and genetically distinct from those previously mapped. The family has two major branches which both descend from the paternal grandparents of President Abraham Lincoln. Among those examined, 56 individuals have a generally non-life threatening cerebellar ataxia. Disease onset varies from 10-68 years and anticipation is evident. We have mapped this gene, spinocerebellar ataxia type 5 (SCA5), to the centromeric region of chromosome 11.

Adolescent↗

PubMed1984

Partial immunochemical characterization of the Ro and La proteins using antibodies from patients with the sicca syndrome and lupus erythematosus.

Ro and La are intracellular ribonucleoproteins that are frequent targets for autoantibodies in the sicca syndrome and in lupus erythematosus. We analyzed the m.w. of the protein (antigen) moieties of Ro and La in saline cell extracts of human spleen by SDS-PAGE and immunoblotting, gel filtration, and sucrose density ultracentrifugation with radioimmunoassay. pI values for Ro and La proteins were established by isoelectric focusing on thin layer agarose gels and immunoblotting on nitrocellulose transfers. The La protein had an m.w. of approximately 43 kd and was heterogeneous in charge, with pI values from 4.2 to 4.8. Composite two-dimensional maps developed by immunoblotting revealed a characteristic set of seven dots of m.w. 43 kd. Ro determinants were identified on polypeptides of 50 and/or 57 kd. Antigenic activity was also detected in the void volume of spleen extract fractionated by Sephadex G-200 and in 8 to 9S and greater than 19S regions of sucrose gradients, suggesting either aggregation of the Ro protein or participation in protein-protein complexes. pI values of 4.3 to 5.5 were obtained for the Ro antigen, and two-dimensional maps revealed that the 57 kd polypeptide had a similar charge heterogeneity to the La protein, whereas the 50 kd polypeptide had a different fingerprint. Immunoblotting of extracts from bovine, rabbit, and dog extracts showed that antibodies to Ro and La reacted with a limited number of polypeptides (m.w. 50 and/or 57 kd for anti-Ro and 43 or 50 kd for anti-La). These studies support the physical independence of the isolated Ro and La polypeptides, although a precursor product or functional relationship in vivo is possible. These studies also suggest that, in addition to Western blotting, techniques involving immunodeletion, isoelectric focusing with capillary immunoblotting, and 2D immunoblotting provide useful approaches to characterize saline-soluble cellular antigens.

Antigens↗

PubMed1996

Genetic and physical mapping at the limb-girdle muscular dystrophy locus (LGMD2B) on chromosome 2p.

The limb-girdle muscular dystrophies (LGMD) are a genetically heterogeneous group of disorders, different forms of which have been mapped to at least six distinct genetic loci. We have mapped an autosomal recessive form of LGMD (LGMD2B) to chromosome 2p13. Two other conditions have been shown to map to this region or to the homologous region in mouse: a gene for a form of autosomal recessive distal muscular dystrophy, Miyoshi myopathy, shows linkage to the same markers on chromosome 2p as LGMD2B, and an autosomal recessive mouse mutation mnd2, in which there is rapidly progressive paralysis and muscle atrophy, has been mapped to mouse chromosome 6 to a region showing conserved synteny with human chromosome 2p12-p13. We have assembled a 6-cM YAC contig spanning the LGMD2B locus and have mapped seven genes and 13 anonymous polymorphic microsatellites to it. Using haplotype analysis in the linked families, we have narrowed our region of interest to a 0-cM interval between D2S2113 and D2S2112/D2S145, which does not overlap with the critical region for mnd2 in mouse. Use of these most closely linked markers will help to determine the relationship between LGMD2B and Miyoshi myopathy. YACs selected from our contig will be the starting point for the cloning of the LGMD2B gene and thereby establish the biological basis for this form of muscular dystrophy and its relationship with the other limb-girdle muscular dystrophies.

Animals↗

PubMed2004

Haplotype sharing correlation analysis using family data: a comparison with family-based association test in the presence of allelic heterogeneity.

The haplotype-sharing correlation (HSC) method for association analysis using family data is revisited by introducing a permutation procedure for estimating region-wise significance at each marker on a study segment. In simulation studies, the HSC method has a correct type 1 error rate in both unstructured and structured populations. The HSC signals on disease segments occur in the vicinity of a true disease locus on a restricted region without recombination hotspots. However, the peak signal may not pinpoint the true disease location in a small region with dense markers. The HSC method is shown to have higher power than single- and multilocus family-based association test (FBAT) methods when the true disease locus is unobserved among the study markers, and especially under conditions of weak linkage disequilibrium and multiple ancestral disease alleles. These simulation results suggest that the HSC method has the capacity to identify true disease-associated segments under allelic heterogeneity that go undetected by the FBAT method that compares allelic or haplotypic frequencies.

Alleles↗

PubMed1983

A physical map of the group A streptococcal pyrogenic exotoxin bacteriophage T12 genome.

A physical map of group A streptococcal bacteriophage T12 was constructed with restriction endonucleases Sal/I, PstI, and EcoRI. The map is circularly permuted with a total length of 36.0 kb. Sub-molar quantities of certain restriction fragments, some of very precise MW and some of heterogeneous MW, were observed. This observation, together with mapping data, suggests that DNA packaging is initiated at a precise site on a concatemeric precursor and proceeds for a limited number of rounds.

Bacterial Proteins↗

PubMedDate not supplied

DFNB20: a novel locus for autosomal recessive, non-syndromal sensorineural hearing loss maps to chromosome 11q25-qter.

Autosomal recessive non-syndromal deafness is an extremely heterogeneous condition with at least 19 loci (DFNB1-19) already described. We have used autozygosity mapping to localise a further novel locus, DFNB20, to chromosome 11q25-qter in a consanguineous family originating from Pakistan. A region of homozygosity was observed in affected individuals spanning the interval D11S969-qter.

Chromosome Mapping↗

PubMed2004

Validation of a thermographic guidewire for endoluminal mapping of atherosclerotic disease: an in vitro study.

Temperature heterogeneity along the inner surface of an artery may be a surrogate marker of impending plaque rupture and has been associated with an increased likelihood of future coronary events. Initial studies using catheter-based thermographic devices have demonstrated that the changes in temperature are subtle, while the effects of coronary flow on measured temperature have not yet been examined. A novel guidewire-based system (ThermoCoil, Imetrx) designed to measure surface temperature in coronary arteries was used to study the effects of heat source intensity and flow on measured temperature. An in vitro model of a focal, eccentric, heat-generating lesion demonstrated that a guidewire-based system can detect changes in surface temperature with a precision of less than 0.08 degrees C. In this model, temperature measurements increased linearly with source temperature and decreased with increases in flow by an exponent of -0.33 (P < 0.001 for both). Flow rates and heat source properties can significantly influence the measurement and interpretation of thermographic data. The incorporation of 2D thermographic images may contribute further to the characterization of metabolically active plaques likely to cause acute coronary syndromes.

Artificial Intelligence↗

PubMed1997

Genetic heterogeneity in Schwartz-Jampel syndrome: two families with neonatal Schwartz-Jampel syndrome do not map to human chromosome 1p34-p36.1.

Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive disorder characterised by the presence of myotonia with a mask-like face, skeletal dysplasia, and growth retardation. Two types have been defined by the age of manifestation of the symptoms. Linkage of Schwartz-Jampel syndrome to human chromosome 1p34-p36.1 has been shown in families where probands presented during infancy or early childhood. We have investigated two well documented families segregating severe neonatal SJS with microsatellite markers spanning the critical region of 1p34-p36. No demonstrable linkage to chromosome 1 was found in either family, suggesting that a second locus is responsible for the severe form of neonatal Schwartz-Jampel syndrome.

Chromosomes, Human, Pair 1↗

PubMed1997

Genetic heterogeneity of familial atrial myxoma syndromes (Carney complex).

Familial atrial myxomas may present as a component of the Carney complex, an autosomal dominant multiple neoplasia and lentiginosis syndrome. Although a gene defect for the Carney complex in some families maps to chromosome 2p, this syndrome is genetically heterogeneous, and other genetic loci also produce familial atrial myxomas.

Adult↗

PubMed2001

Expression of microtubule-associated protein 2 in benign and malignant melanocytes: implications for differentiation and progression of cutaneous melanoma.

Cutaneous melanocytic neoplasms are known to acquire variable characteristics of neural crest differentiation. Melanocytic nevus cells in the dermis and desmoplastic melanomas often display characteristics of nerve sheath differentiation. The extent and nature of neuronal differentiation characteristics displayed by primary and metastatic melanoma cells are not well understood. Here, we describe induction of a juvenile isoform of microtubule-associated protein 2 (MAP-2c) in cultured metastatic melanoma cells by the differentiation inducer hexamethylene bisacetamide. Up-regulation of this MAP-2 isoform, a marker for immature neurons, is accompanied by extended dendritic morphology and down-regulation of tyrosinase-related protein 1 (TYRP1/gp75), a melanocyte differentiation marker. In a panel of cell lines that represent melanoma tumor progression, MAP-2c mRNA and the corresponding approximately 70-kd protein could be detected predominantly in primary melanomas. Immunohistochemical analysis of 61 benign and malignant melanocytic lesions showed abundant expression of MAP-2 protein in melanocytic nevi and in the in situ and invasive components of primary melanoma, but only focal heterogeneous expression in a few metastatic melanomas. In contrast, MAP-2-positive dermal nevus cells and the invasive cells of primary melanomas were TYRP1-negative. This reciprocal staining pattern in vivo is similar to the in vitro observation that induction of the neuronal marker MAP-2 in metastatic melanoma cells is accompanied by selective extinction of the melanocytic marker TYRP1. Our data show that neoplastic melanocytes, particularly at early stages, retain the plasticity to express the neuron-specific marker MAP-2. These observations are consistent with the premise that both benign and malignant melanocytes in the dermis can express markers of neuronal differentiation.

Acetamides↗

PubMed1995

Analysis of the CMT1A-REP repeat: mapping crossover breakpoints in CMT1A and HNPP.

The CMT1A-REP repeat sequence flanks a 1.5 megabase pair (Mb) segment of chromosome 17p11.2-12 which is duplicated in Charcot-Marie-Tooth neuropathy type 1A (CMT1A) and deleted in hereditary neuropathy with liability to pressure palsies (HNPP). The CMT1A-REP repeat is proposed to mediate misalignment and unequal crossover resulting in reciprocal chromosomal rearrangements in CMT1A and HNPP. We have constructed a physical map of the proximal and distal CMT1A-REP repeats. Cloned fragments from CMT1A-REP repeat regions are used to determine the size of the repeats and assess regions of homology. The crossover breakpoints were mapped in series of 30 unrelated CMT1A patients and 22 unrelated HNPP patients. The CMT1A-REP repeat spans approximately 27 kilobase pairs and appears to be continuous. Locations of restriction enzyme sites are highly conserved for the proximal and distal CMT1A-REP repeats. All crossovers mapped within the CMT1A-REP repeat sequence and heterogeneity for breakpoint location demonstrated. Seventy-seven percent (40 to 52) of CMT1A and HNPP chromosomes contained breakpoints which mapped within a 7.9 kb interval, suggesting the presence of a possible 'hotspot'for recombination in CMT1A-REP. DNA sequence analysis for 4 kb of the interval containing the majority of crossovers revealed over 98% sequence identity between proximal and distal CMT1A-REP repeat sequences. Probes useful for molecular-based diagnosis of CMT1A and HNPP are described.

Charcot-Marie-Tooth Disease↗