Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Association mapping”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 469 records · Page 26Linked to original sources
PubMed1993

Functional topography of the myelin-associated glycoprotein. I. Mapping of domains by electron microscopy.

The functional topography of the myelin-associated glycoprotein (MAG) was investigated by electron microscopic analysis of rotary-shadowed molecules of a MAG fragment (MAG 90) comprising the five immunoglobulin-like domains of the extracellular part of the molecule. MAG 90 molecules appeared as rod-like structures (18.5 +/- 1.2 nm long and 4.0 +/- 0.8 nm wide) with a globular domain at one end. Antibodies directed against the amino- and carboxy-terminus of MAG 90 interacted with the non-globular terminal region, indicating that the molecule is bent in the globular region with the amino- and carboxy-terminal arms in close apposition to each other. An antibody which interferes with the binding of MAG to neurons interacted predominantly with the globular domain of MAG 90. The fibril-forming collagen types I, III and V bound mainly to the non-globular terminal region of MAG 90, whereas the majority of heparin molecules interacted with the globular region of the molecule. The L2/HNK-1 carbohydrate structure was localized at the non-globular region in the protein fragment comprising the fourth and fifth immunoglobulin-like domains.

Animals↗
PubMed1985

Analysis of the microtubule-binding domain of MAP-2.

We examined the microtubule-binding domain of the microtubule-associated protein (MAP), MAP-2, using rabbit antibodies that specifically bind to the microtubule-binding region ("stub") and the projection portion ("arm") of MAP-2. We found that (a) microtubules decorated with arm antibody look similar to those labeled with whole unfractionated MAP antibody, though microtubules are not labeled with stub antibody; (b) incubation of depolymerized microtubule protein with stub antibody prior to assembly partially inhibits the rate of microtubule elongation, presumably because MAPs that are complexed with antibody cannot bind to microtubules and stabilize elongating polymers; (c) the rate of appearance and amounts of 36- and 40-kD microtubule-binding peptides produced by digestion with chymotrypsin are distinct for MAPs associated with microtubules vs. MAPs free in solution. The enhanced stability of the 40-kD peptide when associated with microtubules suggests that this domain of the protein is closely associated with, or partially buried in, the microtubule surface; (d) MAP-2 is a slender, elongate molecule as determined by unidirectional platinum shadowing (90 +/- 30 nm), which is in approximate agreement with previous observations. Stub antibody labels MAP-2 in the terminal one-quarter of the extended protein, indicating an intrinsic asymmetry in the molecule.

Animals↗
PubMed1994

The MAP kinase Fus3 associates with and phosphorylates the upstream signaling component Ste5.

Activation of the Saccharomyces cerevisiae MAP kinase Fus3 is thought to occur via a linear pathway involving the sequential action of three proteins: Ste5, a protein of unknown function, Ste11, a MAPKK kinase homolog, and Ste7, a MAPK kinase homolog which phosphorylates and activates Fus3. In this report, we present evidence for a novel mechanism of Fus3 activation that involves a direct association with Ste5, a protein not predicted to interact with Fus3. First, overexpression of Ste5 suppresses fus3 point mutations in an allele-specific manner and increases Fus3 kinase activity in vitro. Second, Ste5 associates with Fus3 in vivo as demonstrated by the two-hybrid system and by two methods of copurification. Third, Ste5 and Fus3 associate prior to pheromone stimulation even when Fus3 is inactive, and in strains lacking Ste7 and Ste11. Fourth Ste5 is phosphorylated by Fus3 in purified complexes and copurifies with an additional protein kinase(s). These observations suggest the possibility that Ste5 promotes signal transduction by tethering Fus3 to its activating protein kinase(s).

Adaptor Proteins, Signal Transducing↗
PubMed2000

Sustaining olfaction at low salinities: mapping ion flux associated with the olfactory sensilla of the blue crab Callinectes sapidus.

To test the hypothesis of a diffusion-generated, ionic/osmotic microenvironment within the olfactory sensilla (aesthetascs), flux gradients of Ca(2+) and K(+) associated with the external surfaces of these sensilla were spatially mapped using self-referencing, ion-selective microelectrodes. Blue crabs (Callinectes sapidus) acclimated to low-salinity conditions (15% sea water and fresh water) showed a net efflux of ions from the aesthetascs. The region of maximum flux associated with each aesthetasc conformed to that predicted from structural data and corresponded to the permeable region of the cuticle separating the olfactory dendrites from the external environment. Estimates of net flux from the entire tuft of aesthetascs for both Ca(2+) and K(+) fell within the predicted range on the basis of comparisons with (22)Na(+) flux measured previously and assuming a passive diffusion model of ion movement from the hemolymph to the sensillar lymph and, ultimately, to the external environment. The maximum concentrations of these ions measured deep within the tuft are discussed in the light of a potential across the aesthetascs that may limit ion efflux at low salinities.

Animals↗
PubMed1994

Identification of latency-associated transcripts that map antisense to the ICP4 homolog gene of Marek's disease virus.

Two small RNAs (0.9 and 0.75 kb), named Marek's disease virus (MDV) small RNAs (MSRs) and a 10-kb RNA, all of which map antisense to the MDV ICP4 homolog gene, have been readily detected in MDCC-MSB1 MDV-transformed T-lymphoblastoid cells. These RNAs were not detectable in reticuloendotheliosis virus-transformed T cells. When MDV was reactivated by treatment of lymphoblastoid cells with 25 micrograms of iododeoxyuridine per ml, the relative levels of the transcripts decreased. These RNAs were not detected by Northern (RNA) hybridization in productively infected chicken embryo fibroblasts 48 h postinfection; however, they were apparent 140 h postinfection. By using Northern hybridization, RNase protection assays, and primer extension analysis, the MSRs were determined to map antisense to the predicted translational start site of the ICP4 homolog gene. The conclusion most consistent with the data is that the two MSRs are overlapping, spliced RNAs. Both small RNAs contain a latency promoter binding factor consensus recognition sequence located toward their 5' ends as well as two potential ICP4 recognition consensus sequences, one in each orientation. The region contains a number of small open reading frames on each side and within the MSRs. Although the exact endpoints are unknown, the large 10-kb species spans the entire ICP4 homolog region. We believe that this group of RNAs, which map antisense to the ICP4 homolog gene, are latency-associated transcripts of MDV.

Animals↗
PubMed1995

Screening a 2 cM genetic map for allelic association: a simulated oligogenic trait.

In this paper, we explore the use of a variety of familial transmission tests (and case-control analyses) to screen for allelic associations in simulated marker data of a quality (2 cM map) that will feasibly arise from genomic scans within the next 5-10 years. We demonstrate a form of the transmission-disequilibrium test extended to multiallele systems. The methods used were log-linear and related models implemented largely using standard statistical packages.

Alleles↗
PubMed1993

Network analysis of functional auditory pathways mapped with fluorodeoxyglucose: associative effects of a tone conditioned as a Pavlovian excitor or inhibitor.

The purpose of this study was to examine how opposite learned associative properties of the same auditory stimulus are represented by the pattern of network interactions between auditory system structures. [14C(U)]2-fluoro-2-deoxyglucose (FDG) autoradiography was used to compare mean auditory system activity and interregional correlations resulting from the presentation of a tone trained as either a Pavlovian conditioned excitor or inhibitor. Rats were trained with reinforced trials of the conditioned excitor (A+) intermixed with non-reinforced trials of a tone-light compound (AX-). For the Conditioned Excitor group, the tone was the excitor (A+), while for the Conditioned Inhibitor group the tone was the inhibitor (X-). After conditioning, both groups were injected with FDG and presented with the same tone. Structural equation models, constructed from the anatomical connections between auditory regions and their interregional correlations in FDG uptake, were used to calculate path coefficients representing the network interactions. The opposite associative significance of the tone was reflected as functional changes in the interactions between parallel auditory pathways. Direct covariance effects through lemniscal pathways from the ventral cochlear nucleus were similar in absolute magnitude but differed in sign between the Excitor and Inhibitor network models. Extra-auditory influences on the dorsal cochlear nucleus were greater for the tone-inhibitor, reflecting possible interactions of this nucleus with extra-auditory regions. The different associative effects of the tone suggest that central auditory pathways can code not only the physical qualities, but also the associative significance of auditory stimuli. These findings demonstrate that neural network interactions differentiate the associative effects of tones in the brain. It is proposed that associative learning is a distributed property of neural networks and that such a property can be understood by considering the interactions between component parts of the network.

Acoustic Stimulation↗
PubMed2003

Mapping quantitative trait loci associated with resistance to coccidiosis and growth.

To map QTL associated with disease resistance to avian coccidiosis and growth, two commercial broiler lines with different degrees of resistance to the disease were crossed to generate an F1 generation that was intercrossed to produce 314 F2 generation offspring. The F2 offspring were inoculated with sporulated oocysts of Eimeria maxima. Five disease-associated phenotypes were measured after the infection. Intertrait comparisons revealed that oocyst shedding was a good parameter for evaluating disease resistance or susceptibility. One hundred nineteen microsatellite markers, covering 80% of the chicken genome with an average marker interval of 25 cM, were used for genotyping of F1 parents and F2 offspring. Statistical analysis based on the data of four families revealed a locus on chromosome 1 associated with oocyst shedding (logarithm of odds = 3.46). The genetic mechanism of this locus appeared additive. The genomic scan also identified three potential growth QTL on chromosomes 1, 6, and 8. These results provide the foundation for further investigation to validate the QTL.

Animals↗
PubMed1987

The myelin-associated glycoprotein gene: mapping to human chromosome 19 and mouse chromosome 7 and expression in quivering mice.

Myelin-associated glycoprotein (MAG), a membrane glycoprotein of 100 kDa, is thought to be involved in the process of myelination. A cDNA encoding the amino-terminal half of rat MAG has recently been isolated and sequenced. We have used this cDNA in Southern blot analysis of DNA from 32 somatic cell hybrids to assign the human locus for MAG to chromosome 19 and the mouse locus to chromosome 7. Since the region of mouse chromosome 7-known to contain several other genes that are homologous to genes on human chromosome 19-also carries the quivering (qv) locus, we considered the possibility that a mutation in the MAG gene could be responsible for this neurological disorder. While MAG-specific DNA restriction fragments, mRNA, and protein from qv/qv mice were apparently normal in size and abundance, we have not ruled out the possibility that qv could be caused by a point mutation in the MAG gene.

Animals↗
PubMed2005

A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene.

PURPOSE: The purpose of this paper is to map the locus for a variant form of Oguchi disease in a Pakistani family and to identify the causative mutation. METHODS: Family 61029 was ascertained in the Punjab province of Pakistan. It includes three 13- to 19-year-old patients with night blindness and 12 unaffected family members. A complete ophthalmological examination including fundus photography and electroretinography (ERG) was performed on each family member. A genome-wide scan was performed using microsatellite markers at about 10 cM intervals, and two-point lod scores were calculated. Polymerase chain reaction (PCR) cycle dideoxynucleotide sequencing was used to screen candidate genes inside the linked region for mutations and to delineate the deletion. Multiplex PCR and long template PCR were used to detect deletions and to define the size of deletions. Evaluation of fundus changes and ERG, lod score estimation, and identification of a mutation in the GRK1 gene were carried out. RESULTS: All patients had night blindness since early childhood. Irregular coarse pigmentation was observed in the peripheral retina of each patient. The fundus appearance before and after 4 h of dark adaptation was similar except that the peripheral retinal pigmentary changes were slightly less evident after extended dark adaptation. Minimal or no rod function with normal cone function on ERG recordings were detected in all three affected members. The rod showed slow recovery to nearly normal amplitude after 4 h in the dark ERG in one individual but not in two other patients. A genome-wide scan showed linkage only to D13S285. Fine mapping defined a region from D13S1315 to 13qter, with a lod score of 2.89 at theta=0 shown by D13S285 and 2.90 at theta=0 by the D13S261-D13S285-D13S1295-D13S293 haplotype. Analysis of the GRK1 gene, which is included in this interval, identified a c.827+623_883del mutation. This intragenic deletion cosegregates with the disease in the family and is only homozygous in affected individuals. This mutation was not detected in 96 controls. CONCLUSIONS: The retinal disease in the family reported here has several features differing from typical Oguchi disease, including an atypical Mizuo-Nakamura phenomenon and a non-recordable rod ERG even after 4 h of dark adaptation. Normal visual acuity, normal caliber of retinal blood vessels, and normal cone response on ERG recording suggest retinal dysfunction rather than degeneration (i.e., a variant form of Oguchi disease but unlikely to be retinitis pigmentosa). The disease in the Pakistani family localizes to 13q34 and is caused by a novel deletion including Exon 3 of the GRK1 gene.

Adolescent↗
PubMed1985

Ontogenetic changes in the cyclic adenosine 3',5'-monophosphate-stimulatable phosphorylation of cat visual cortex proteins, particularly of microtubule-associated protein 2 (MAP 2): effects of normal and dark rearing and of the exposure to light.

Based on a theory that a norepinephrine-stimulated cascade of events resulting in an increase of intracellular cyclic adenosine 3',5'-monophosphate (cAMP) modulates the state of plasticity for the receptive field property of visual cortical neurons, we have followed the ontogenetic changes in cAMP-stimulated phosphorylation of proteins in whole homogenates obtained from developing visual cortices of cats. In vitro phosphorylation was assayed with and without cAMP and the cAMP-dependent protein kinase, and the phosphoproteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were counted for 32P incorporated from [gamma-32P]ATP. It was found that the regulatory subunits of the cAMP-dependent protein kinase are present and fully active by birth, whereas the synapsin content increases at a rate concomitant with synaptogenesis. These ontogenetic developments are not influenced by dark rearing (DR) from birth, a procedure which postpones the onset of the critical period (CP) for plasticity. By contrast, the cAMP-stimulatable phosphorylation of microtubule-associated protein 2 (MAP 2), which under normal rearing conditions increases from birth to the second month, is strongly modulated by the presence of light in the environment. After DR for various periods, kittens were subsequently exposed to light so as to trigger the onset of the CP that had been postponed. A few hours of light were sufficient to cause a large increase in the in vitro phosphorylation of MAP 2. This effect is not observed in the auditory cortex or the lateral geniculate nucleus of the same animals, or in the visual cortex of normally reared cats which were then dark reared in adulthood. But this effect was seen in the visual cortices of cats following 5 months of DR from birth, animals which by chronological age have passed the CP, presumably because the onset of the CP was extended by the DR procedure. The cAMP-dependent phosphorylation of MAP 2 (and its dephosphorylation) may be an important factor for determining the state of plasticity in the CP through its affecting the dendritic cytoskeletal organization involving tubulin and actin.

Aging↗
PubMed1991

Addition of protease inhibitors to culture medium of neuroblastoma cells induces both neurite outgrowth and phosphorylation of microtubule-associated protein MAP-1B.

The addition of two synthetic peptides with antiprotease activity to the culture medium of mouse neuroblastoma cells results in the promotion of neurite outgrowth. One of these peptides has a sequence corresponding to the reactive center of protease nexin-1 and inhibits both trypsin and thrombin. Its effect on neuroblastoma cells is similar to that found on serum withdrawal from the culture medium, giving rise to cells with one or two long neurites, and is reversed upon the addition of thrombin to the culture medium. The sequence of the other peptide is present in one of the precursor proteins of the main component of the amyloid plaques of Alzheimer's disease patients' brains, and corresponds to protease nexin-2. It can inhibit trypsin but fails to inhibit thrombin at low doses. Its effect on neuroblastoma cells is slightly different from that observed after serum deprivation, as a significant proportion of stellate cells, with short and branched neurites, is observed. An increase in the phosphorylation of microtubule-associated protein MAP-1B, which accompanies neurite outgrowth induced by serum deprivation, is also observed upon addition of the two antiprotease synthetic peptides, although the nexin-2 (amyloid) peptide induces a less marked increase in phosphorylated MAP-1B than does the nexin-1 peptide. These results may be correlated with the different antiprotease activities of both synthetic peptides, thus suggesting a role for a balance between trypsin-like and thrombin-like proteases and their inhibitors in eliciting neurite outgrowth under normal and pathological conditions.

Alzheimer Disease↗
PubMed1990

Mapping of mutations associated with neurovirulence in monkeys infected with Sabin 1 poliovirus revertants selected at high temperature.

Poliovirus type 1 neurovirulence is difficult to analyze because of the 56 mutations which differentiate the neurovirulent Mahoney strain from the attenuated Sabin strain. We have isolated four neurovirulent mutants which differ from the temperature-sensitive parental Sabin 1 strain by only a few mutations, using selection for temperature resistance: mutant S(1)37C1 was isolated at 37.5 degrees C, S(1)38C5 was isolated at 38.5 degrees C, and S(1)39C6 and S(1)39C10 were isolated at 39.5 degrees C. All four mutants had a positive reproductive capacity at supraoptimal temperature (Rct+ phenotype). Mutant S(1)37C1 induced paralysis in two of four cynomolgus monkeys, and the three other mutants induced paralysis in four of four monkeys. The lesion score increased from the S(1)37C1 mutant to the S(1)39 mutants. To map the mutations associated with thermoresistance and neurovirulence, we sequenced all regions in which the Sabin 1 genome differs from the Mahoney genome. The S(1)37C1 mutant had one mutation in the 5' noncoding region and another in the 3' noncoding region. Mutant S(1)38C5 had these mutations plus another mutation in the 3D polymerase gene. The S(1)39 mutants had three additional mutations in the capsid protein region. The mutations were located at positions at which the Sabin 1 and Mahoney genomes differ, except for the mutation in the 5' noncoding region. The noncoding-region mutations apparently confer a low degree of neurovirulence. The 3D polymerase mutation, which distinguishes S(1)38C5 and S(1)39 mutants from S(1)37C1, is probably responsible for the high neurovirulence of S(1)38C5 and S(1)39 mutants. The capsid region mutations may contribute to the neurovirulence of the S(1)39 mutants, which was the highest among the mutants.

Animals↗
PubMed1980

Simian virus 40-associated small RNA: mapping on the simian virus 40 genome and characterization of its synthesis.

The simian virus 40 (SV40)-associated small RNA (SAS-RNA) has previously been shown to arise late in SV40 lytic infection and to bear homology with the SV40 early mRNA's, or the SV40 genome, at map position 0.21. By using hybridization analysis, we determined that the SAS-RNA is between 62 and 65 nucleotides in length and its homology region lies between nucleotides 2760 and 2825 of the SV40 late(+) DNA strand. Viable deletion mutants which lacked part or all of this region made no SAS-RNA, strongly indicating that this is the coding region of the SAS-RNA. The expected sequence for the SAS-RNA, determined from the DNA sequence between nucleotides 2760 and 2825, appeared to be very pyrimidine rich (76% uridine and cytidine). Deletion or alteration of sequences immediately preceding the SAS-RNA coding region (approximately nucleotides 2716 to 2748) resulted in the loss of SAS-RNA production. These sequences may be part of a promotor for SAS-RNA synthesis or a processing site for its excision from long nuclear late transcripts. Under growth conditions where late transcription was not fully initiated (tsA58 at 41 degrees C; wild-type SV40 in the presence of 1-beta-D-arabinofuranosylcytosine), no SAS-RNA was produced, indicating that the expression of the SAS-RNA is regulated by a mechanism related to the control of late transcription.

Base Sequence↗
PubMed2005

Contour interactions between pairs of Gabors engaged in binocular rivalry reveal a map of the association field.

A psychophysical study was conducted to investigate contour interactions (the 'association field'). Two Gabor patches were presented to one eye, with random-dot patches in corresponding locations of the other eye so as to produce binocular rivalry. Perceptual alternations of the two rivalry processes were monitored continuously by observers and the two time series were cross-correlated. The Gabors were oriented collinearly, obliquely, or orthogonally, and spatial separation was varied. A parallel condition was also included. Correlation between the rivalry processes strongly depended on separation and relative orientation. Correlations between adjacent collinear Gabors was near-perfect and reduced with spatial separation and as relative orientation departed from collinear. Importantly, variations in cross-correlation did not alter the rivalry processes (average dominance duration, and therefore alternation rate, was constant across conditions). Instead, synchronisation of rivalry oscillations accounts for the correlation variations: rivalry alternations were highly synchronised when contour interactions were strong and were poorly synchronised when contour interactions were weak. The level of synchrony between these two stochastic processes, in depending on separation and relative orientation, effectively reveals a map of the association field. These association fields are not greatly affected by contrast, and can be demonstrated between contours that are presented to separate hemispheres.

Computer Graphics↗
PubMed1986

On the identification of the rosy locus DNA in Drosophila melanogaster: intragenic recombination mapping of mutations associated with insertions and deletions.

DNA extracts of several rosy-mutation-bearing strains were associated with large insertions and deletions in a defined region of the molecular map believed to include the rosy locus DNA. Large-scale, intragenic mapping experiments were carried out that localized these mutations within the boundaries of the previously defined rosy locus structural element. Molecular characterization of the wild-type recombinants provides conclusive evidence that the rosy locus DNA is localized to the DNA segment marked by these lesions. One of the mutations, ry2101, arose from a P-M hybrid dysgenesis experiment and is associated with a copia insertion. Experiments are described which suggest that copia mobilizes in response to P-M hybrid dysgenesis. Relevance of the data to recombination in higher organisms is considered.

Animals↗
PubMed1999

c-Myc transactivation domain-associated kinases: questionable role for map kinases in c-Myc phosphorylation.

We have isolated and characterized cellular kinases which associate with the transactivation domain of c-Myc and phosphorylate Ser-62. We demonstrate that cellular Map kinases associate with c-Myc under stringent conditions and phosphorylate Ser-62. We also find that TPA stimulates the activity of the Myc-associated Map kinase to phosphorylate Ser-62. However, we do not observe an increase in Ser-62 phosphorylation in endogenous c-Myc after TPA treatment of cells. Since the regulation of the c-Myc-associated Map kinases does not correlate with the in vivo regulation of Ser-62 phosphorylation in c-Myc, we conclude that Map kinases are not the in vivo kinases for Ser-62. Although Ser-62 phosphorylation was not affected by TPA, phosphorylation at a different serine residue was significantly upregulated by TPA.

3T3 Cells↗