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At least 73 records · Page 4Linked to original sources
PubMed2003

Combined high resolution linkage and association mapping of quantitative trait loci.

In this paper, we investigate variance component models of both linkage analysis and high resolution linkage disequilibrium (LD) mapping for quantitative trait loci (QTL). The models are based on both family pedigree and population data. We consider likelihoods which utilize flanking marker information, and carry out an analysis of model building and parameter estimations. The likelihoods jointly include recombination fractions, LD coefficients, the average allele substitution effect and allele dominant effect as parameters. Hence, the model simultaneously takes care of the linkage, LD or association and the effects of the putative trait locus. The models clearly demonstrate that linkage analysis and LD mapping are complementary, not exclusive, methods for QTL mapping. By power calculations and comparisons, we show the advantages of the proposed method: (1) population data can provide information for LD mapping, and family pedigree data can provide information for both linkage analysis and LD mapping; (2) using family pedigree data and a sparse marker map, one may investigate the prior suggestive linkage between trait locus and markers to obtain low resolution of the trait loci, because linkage analysis can locate a broad candidate region; (3) with the prior knowledge of suggestive linkage from linkage analysis, both population and family pedigree data can be used simultaneously in high resolution LD mapping based on a dense marker map, since LD mapping can increase the resolution for candidate regions; (4) models of high resolution LD mappings using two flanking markers have higher power than that of models of using only one marker in the analysis; (5) excluding the dominant variance from the analysis when it does exist would lose power; (6) by performing linkage interval mappings, one may get higher power than by using only one marker in the analysis.

Chromosome Mapping↗
PubMed2005

In silico analysis of disease-association mapping strategies using the coalescent process and incorporating ascertainment and selection.

We present a new method for simulating samples of marker haplotypes, genotypes, or diplotypes in case-control studies in which the markers are linked to a disease locus in any specified region of the genome. The method allows realistic features to be incorporated into the simulations, including selection acting on disease alleles, sample ascertainment of disease chromosomes and polymorphic markers, a genetic dominance model of disease expression that allows incomplete penetrance and phenocopies, and an accurate genetic map of recombination rates and hotspots for recombination in the human genome (or, alternatively, an improved method for simulating the distribution of hotspots). The new method uses an approach that combines simulation of the coalescent process for the sampled chromosomes with a diffusion process used to model the evolution of the disease-mutation frequency over time. Examples illustrate how the method may be used to study the expected power of a marker-disease association study.

Alleles↗
PubMed2001

Quantitative trait loci mapping associated with plant regeneration ability from seed derived calli in rice (Oryza sativa L.).

Quantitative trait loci (QTLs), which are associated with the ability of plant regeneration from seed derived calli, were detected using a recombinant inbred (RI) population from a cross between 'Milyang 23 (toingil)' and 'Gihobyeo (japonica)' in rice (Oryza sativa L.). A tongil type cultivar, 'Milyang 23', has a lower frequency of callus induction and plant regeneration than those of japonica 'Gihobyeo'. Transgressive segregations were observed for the callus induction rate and plant regeneration ability from seed derived calli of the RI population. An interval mapping analysis was used to identify the QTL controlling the plant regeneration ability. Two QTLs for the callus induction rate were detected on chromosomes 1 and 2, explaining the 10.9% total phenotypic variation. Four QTLs that are associated with the plant regeneration ability were located on chromosomes 2, 3, and 11, accounting for 25.7% of the total phenotypic variation.

Chromosome Mapping↗
PubMed2005

Gadobenate dimeglumine-enhanced MR imaging breast vascular maps: association between invasive cancer and ipsilateral increased vascularity.

PURPOSE: To retrospectively compare three different doses of gadobenate dimeglumine with a standard dose of gadopentetate dimeglumine for magnetic resonance (MR) imaging evaluation of breast vessels and to evaluate the accuracy of one-sided increased vascularity seen on gadobenate dimeglumine-enhanced MR images as an indicator of ipsilateral breast cancer. MATERIALS AND METHODS: The original study had local ethics committee approval; informed consent was obtained from all enrolled patients. Ninety-five patients known to have or suspected of having breast cancer were randomly assigned to four groups to receive gadobenate dimeglumine at a dose of 0.05, 0.10, or 0.20 mmol per kilogram of body weight or gadopentetate dimeglumine at a dose of 0.10 mmol/kg. T1-weighted gradient-echo MR images were acquired before and 2 minutes after intravenous contrast material injection. Subtracted images were used to obtain maximum intensity projections (MIPs). Two readers blinded to the type and dose of contrast agent administered scored the MIPs obtained in the dose groups for vessel number, length, and conspicuity from 0, which indicated absent or low breast vascularity, to 3, which indicated high breast vascularity. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of one-sided increased vascularity in association with ipsilateral malignancy for 69 histopathologically confirmed lesions (reference standard) were determined after gadobenate dimeglumine-enhanced MR imaging. RESULTS: The mean MIP scores assigned to the gadobenate dimeglumine groups were significantly higher than those assigned to the gadopentetate dimeglumine group (P < or = .044). Histopathologic analysis revealed malignant lesions in 52 of 69 patients examined with gadobenate dimeglumine MR imaging: invasive ductal carcinoma in 45, invasive lobular carcinoma in four, and invasive mixed ductal-lobular carcinoma in three patients. Seventeen patients had benign lesions. Two cases of bilateral invasive cancer with symmetric breast vascular maps were excluded. Thus, the overall sensitivity, specificity, accuracy, PPV, and NPV of one-sided increased vascularity as a finding associated with ipsilateral malignancy were 88% (44 of 50 patients), 82% (14 of 17 patients), 87% (58 of 67 patients), 94% (44 of 47 patients), and 70% (14 of 20 patients), respectively. CONCLUSION: Gadobenate dimeglumine is effective for MR imaging evaluation of breast vessels at doses as low as 0.05 mmol/kg. One-sided increased vascularity is an MR imaging finding frequently associated with ipsilateral invasive breast cancer.

Adult↗
PubMed2003

Refining the analysis of a whole genome linkage disequilibrium association map: the United Kingdom results.

Individual genotyping of the 10 most promising markers identified in our previously reported screen for linkage disequilibrium (LD) in multiple sclerosis identified a number of effects which confound the analysis and are of general importance in the interpretation of results obtained using microsatellite markers typed in pooled DNA. In order to identify and characterise these effects, we individually genotyped 529 promising markers in 16 trio families. We then devised adapting factors, which were designed to correct for these confounders. This more extensive analysis of the previously published UK data set and the repeat analyses incorporating these adaptations led to the identification of two novel markers that may be associated with multiple sclerosis in this population, providing a close correlation between the results of pooled analysis and individual typing.

Dinucleotide Repeats↗
PubMed2004

Role of ceramide in activation of stress-associated MAP kinases by minimally modified LDL in vascular smooth muscle cells.

Interaction of oxidized low-density lipoprotein (LDL) with arterial smooth muscle cells (SMC) is believed to play a key role in the development of atherosclerosis. Depending on the extent of oxidation, apolipoproteins and/or lipids in the particle may be modified and thus lead to different cellular responses (e.g. proliferation or cell death). Here we report on the signaling effects of LDL, in which only the lipids were oxidized. This so-called minimally modified LDL (mmLDL) mainly activated components involved in stress response and apoptotic cell death including p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase/stress-activated protein kinase (JNK) as well as neutral and acid sphingomyelinase. In contrast, proliferative signaling elements such as extracellular regulated kinase, AKT-kinase and phospho-BAD seem to play a minor role as they were only slightly stimulated by mmLDL. Ceramide, the hydrolysis product of sphingomyelin, seems to be a key mediator as it mimics mmLDL by inducing activation of the same signaling components. Moreover, mmLDL- and ceramide-associated effects on apoptotic protein kinases were abolished by NB6, a specific inhibitor of acid sphingomyelinase. Thus, acid sphingomyelinase is very likely to be primarily responsible for triggering intracellular signal transduction in SMC after exposure to mmLDL via formation of ceramide by an autocatalytic mechanism.

Apoptosis↗
PubMed2005

Geographically weighted Poisson regression for disease association mapping.

This paper describes geographically weighted Poisson regression (GWPR) and its semi-parametric variant as a new statistical tool for analysing disease maps arising from spatially non-stationary processes. The method is a type of conditional kernel regression which uses a spatial weighting function to estimate spatial variations in Poisson regression parameters. It enables us to draw surfaces of local parameter estimates which depict spatial variations in the relationships between disease rates and socio-economic characteristics. The method therefore can be used to test the general assumption made, often without question, in the global modelling of spatial data that the processes being modelled are stationary over space. Equally, it can be used to identify parts of the study region in which 'interesting' relationships might be occurring and where further investigation might be warranted. Such exceptions can easily be missed in traditional global modelling and therefore GWPR provides disease analysts with an important new set of statistical tools. We demonstrate the GWPR approach applied to a data set of working-age deaths in the Tokyo metropolitan area, Japan. The results indicate that there are significant spatial variations (that is, variation beyond that expected from random sampling) in the relationships between working-age mortality and occupational segregation and between working-age mortality and unemployment throughout the Tokyo metropolitan area and that, consequently, the application of traditional 'global' models would yield misleading results.

Adult↗
PubMed2000

Fine scale association mapping of disease loci using simplex families.

We present a new method for the fine scale mapping of disease loci based on samples of simplex families, each containing an affected child. The method is based on a generalisation of a single locus allele transmission model to multiple marker loci. The model is developed under the assumption of a single ancestral mutation and allows for the calculation of posterior probabilities that each allele at a particular marker was present on the founder chromosome. We illustrate the method using simulated family data for cystic fibrosis and Huntingtons disease, for which the locations of mutations in the disease genes are now known. For both diseases, our new method provides good estimates of the location of the mutations.

Alleles↗
PubMed1998

A general RNA-binding protein complex that includes the cytoskeleton-associated protein MAP 1A.

Association of mRNA with the cytoskeleton represents a fundamental aspect of RNA physiology likely involved in mRNA transport, anchoring, translation, and turnover. We report the initial characterization of a protein complex that binds RNA in a sequence-independent but size-dependent manner in vitro. The complex includes a approximately 160-kDa protein that is bound directly to mRNA and that appears to be either identical or highly related to a approximately 1600-kDa protein that binds directly to mRNA in vivo. In addition, the microtubule-associated protein, MAP 1A, a cytoskeletal associated protein is a component of this complex. We suggest that the general attachment of mRNA to the cytoskeleton may be mediated, in part, through the formation of this ribonucleoprotein complex.

Animals↗
PubMed1992

A single step purification for recombinant proteins. Characterization of a microtubule associated protein (MAP 2) fragment which associates with the type II cAMP-dependent protein kinase.

A 167 base pair DNA cassette has been constructed to facilitate the detection and purification of recombinant proteins. This cassette, kfc, encodes three distinct peptide units: a phosphorylation site for the cAMP-dependent protein kinase (PKA), called kemptide, a factor Xa cleavage site, and a calmodulin-binding peptide. Expressed kfc fusion proteins can be purified from bacterial lysates in one step by affinity chromatography on calmodulin-agarose using EGTA as eluant. As a test of this system, we describe the expression, purification and characterization of the PKA binding domain of the microtubule associated protein (MAP 2).

Amino Acid Sequence↗
PubMed1983

Differential distribution of microtubule-associated proteins MAP-1 and MAP-2 in neurons of rat brain and association of MAP-1 with microtubules of neuroblastoma cells (clone N2A).

To study the individual location of the microtubule proteins MAP-1 and MAP-2 in neuronal tissues and cells, antisera to electrophoretically purified MAP-1 and MAP-2 components were raised in rabbits. When frozen sections through rat brain were examined by immunofluorescence microscopy the antibodies to MAP-1 strongly stained a variety of nerve cells including dendrites and myelinated axons in the cerebrum and cerebellum. Antibodies to MAP-2 showed similar staining patterns, except that myelinated axons were unstained. These results were confirmed by immunoelectron microscopy of frozen sections through cerebellum using the peroxidase technique. Thereby, the association of MAP-1 with microtubules was also clearly demonstrated. When cultured mouse neuroblastoma N2A cells were examined by immunofluorescence microscopy the antiserum to MAP-1 brightly stained filamentous structures resembling microtubules, whereas relatively weak and diffuse staining of the cytoplasm was observed with the antiserum to MAP-2. In agreement with the immunolocalization, MAP-1, but not MAP-2, was found as a prominent component of microtubules proteins polymerized in vitro by taxol from soluble N2A cell extracts. Together these results indicate that neuronal microtubules are preferentially associated with distinct high mol. wt. polypeptides. Therefore, they support the concept that different complements of associated proteins determine distinct functions of microtubules.

Animals↗