ORGANIZATION OF THE ROSY LOCUS IN DROSOPHILA MELANOGASTER: EVIDENCE FOR A CONTROL ELEMENT ADJACENT TO THE XANTHINE DEHYDROGENASE STRUCTURAL ELEMENT

Genetics ◽  
1976 ◽  
Vol 84 (2) ◽  
pp. 233-255
Author(s):  
A Chovnick ◽  
W Gelbart ◽  
M McCarron ◽  
B Osmond ◽  
E P M Candido ◽  
...  
Keyword(s):  
Large Scale ◽  
Genetic Basis ◽  
Structural Information ◽  
Natural Populations ◽  
Control Element ◽  
Structural Element ◽  
Electrophoretic Variants ◽  
Cis Acting ◽  
A Site ◽  
Recombination Experiments

ABSTRACT From a collection of electrophoretic variants of XDH obtained from laboratory strains and natural populations, a stock was isolated that was associated with much greater than normal levels of XDH activity. Preliminary recombination experiments demonstrated that this character maps to the rosy locus. While a series of observations failed to relate this phenotype to alteration in the structure of the XDH polypeptide, kinetic and immunological experiments did succeed in associating this character with variation in number of molecules of XDH/fly. Large scale fine structure recombination experiments locate the genetic basis for this variation in number of molecules of XDH/fly to a site very close to, but definitely outside of, the genetic boundaries of the XDH structural information. Observations are described which eliminate the possibility that we are dealing with a tandem duplication of the XDH structural element. Turning to a regulatory role for this genetic element located adjacent to the XDH structural information, a simple experiment is described which demonstrates that it functions as a "cis-acting" regulator of the XDH structural element.

scholarly journals ORGANIZATION OF THE ROSY LOCUS IN DROSOPHILA MELANOGASTER: FURTHER EVIDENCE IN SUPPORT OF A CIS-ACTING CONTROL ELEMENT ADJACENT TO THE XANTHINE DEHYDROGENASE STRUCTURAL ELEMENT

Genetics ◽  
1979 ◽  
Vol 91 (2) ◽  
pp. 275-293
Author(s):  
M McCarron ◽  
J O'Donnell ◽  
A Chovnick ◽  
B S Bhullar ◽  
J Hewitt ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Control Region ◽  
Large Scale ◽  
Present Report ◽  
Xanthine Dehydrogenase ◽  
Control Element ◽  
Genetic Dissection ◽  
Structural Element ◽  
Cis Acting ◽  
A Site

ABSTRACT The present report summarizes our recent progress in the genetic dissection of an elementary genetic unit in a higher organism, the rosy locus (ry: 3-52.0) in Drosophila melanogaster. Pursuing the hypothesis that the rosy locus includes a noncoding control region, as well as a structural element coding for the xanthine dehydrogenase (XDH) peptide, experiments are described that characterize and map a rosy locus variant associated with much lower than normal levels of XDH activity. Experiments are described that fail to relate this phenotype to alteration in the structure of the XDH peptide, but clearly associate this character with variation in number of molecules of XDH per fly. Large-scale fine-structure recombination experiments locate the genetic basis for this variation in the number of molecules of XDH per fly to a site immediately to the left of the XDH structural element within a region previously designated as the XDH control element. Moreover, experiments clearly separate this "underproducer" variant site from a previously described "overproducer" site within the control region. Examination of enzyme activity in electrophoretic gels of appropriate heterozygous genotypes demonstrates the cis-acting nature of this variation in the number of molecules of XDH. A revision of the map of the rosy locus, structural and control elements is presented in light of the additional mapping data now available.

scholarly journals EXTENSION OF THE LIMITS OF THE XDH STRUCTURAL ELEMENT IN DROSOPHILA MELANOGASTER

Genetics ◽  
1976 ◽  
Vol 84 (2) ◽  
pp. 211-232
Author(s):  
William Gelbart ◽  
Margaret McCarron ◽  
Arthur Chovnick
Keyword(s):  
Drosophila Melanogaster ◽  
Control Element ◽  
Null Mutant ◽  
Structural Element ◽  
Electrophoretic Variants ◽  
Structural Alterations ◽  
Eye Color ◽  
Eye Color Mutants ◽  
Interallelic Complementation ◽  
Recombination Experiments

ABSTRACT Experiments expanding the array of mutants affecting the xanthine dehydrogenase (XDH) structural element in Drosophila melanogaster are described. These include rosy eye color mutants which exhibit interallelic complementation, and mutants with normal eye color but lowered levels of XDH. Evidence is presented which argues that these are structural alterations in the enzyme. Recombination experiments were performed using these mutants as well as some electrophoretic variants. The two ends of the rosy locus are marked with mutant sites which are clearly structural in nature; the XDH structural element and the rosy null mutant map are completely concordant. A possible procedure to recover control element mutants is described.

scholarly journals INTRACISTRONIC MAPPING OF ELECTROPHORETIC SITES IN DROSOPHILA MELANOGASTER: FIDELITY OF INFORMATION TRANSFER BY GENE CONVERSION

Genetics ◽  
1974 ◽  
Vol 76 (2) ◽  
pp. 289-299
Author(s):  
Margaret McCarron ◽  
William Gelbart ◽  
Arthur Chovnick
Keyword(s):  
Drosophila Melanogaster ◽  
Information Transfer ◽  
Large Scale ◽  
Genetic Basis ◽  
Xanthine Dehydrogenase ◽  
Specific Protein ◽  
Wild Type ◽  
Electrophoretic Variation ◽  
The Stability ◽  
Recombination Experiments

ABSTRACT A convenient method is described for the intracistronic mapping of genetic sites responsible for electrophoretic variation of a specific protein in Drosophila melanogaster. A number of wild-type isoalleles of the rosy locus have been isolated which are associated with the production of electrophoretically distinguishable xanthine dehydrogenases. Large-scale recombination experiments were carried out involving null enzyme mutants induced on electrophoretically distinct wild-type isoalleles, the genetic basis for which is followed as a nonselective marker in the cross. Additionally, a large-scale recombination experiment was carried out involving null enzyme rosy mutants induced on the same wild-type isoallele. Examination of the electrophoretic character of crossover and convertant products recovered from the latter experiment revealed that all exhibited the same parental electrophoretic character. In addition to documenting the stability of the xanthine dehydrogenase electrophoretic character, this observation argues against a special mutagenesis hypothesis to explain conversions resulting from allele recombination studies.

GENETIC LIMITS OF THE XANTHINE DEHYDROGENASE STRUCTURAL ELEMENT WITHIN THE ROSY LOCUS IN DROSOPHILA MELANOGASTER

Genetics ◽  
1974 ◽  
Vol 78 (3) ◽  
pp. 869-886
Author(s):  
William M Gelbart ◽  
Margaret McCarron ◽  
Janardan Pandey ◽  
Arthur Chovnick
Keyword(s):  
Drosophila Melanogaster ◽  
Amino Acid ◽  
Structural Information ◽  
Xanthine Dehydrogenase ◽  
Gene Organization ◽  
Null Mutant ◽  
Electrophoretic Variation ◽  
Structural Element ◽  
Electrophoretic Variants ◽  
Left And Right

Abstract Experiments are described that provide an opportunity to estimate the genetic limits of the structural (amino acid coding) portion of the rosy locus (3: 52.0) in Drosophila melanogaster, which controls the enzyme, xanthine dehydrogenase (XDH) . This is accomplished by mapping experiments which localize sites responsible for electrophoretic variation in the enzyme on the known genetic map of null-XDH rosy mutants. Electrophoretic sites are distributed along a large portion of the null mutant map. A cis-trans test involving electrophoretic variants in the left- and right-hand portions of the map leads to the conclusion that the entire region between these variants is also structural. Hence most, if not all, of the null mutant map of the rosy locus contains structural information for the amino acid sequence of the XDH polypeptide. Consideration is given to the significance of the present results for the general problem of gene organization in higher eukaryotes.

scholarly journals TISSUE-SPECIFIC AND PRETRANSLATIONAL CHARACTER OF VARIANTS OF THE ROSY LOCUS CONTROL ELEMENT IN DROSOPHILA MELANOGASTER

Genetics ◽  
1984 ◽  
Vol 108 (4) ◽  
pp. 953-968
Author(s):  
S H Clark ◽  
S Daniels ◽  
C A Rushlow ◽  
A J Hilliker ◽  
A Chovnick
Keyword(s):  
Drosophila Melanogaster ◽  
Fat Body ◽  
Present Report ◽  
Malpighian Tubules ◽  
Phenotypic Characterization ◽  
Control Element ◽  
Structural Element ◽  
Tissue Specific ◽  
Cis Acting

ABSTRACT Prior reports from this laboratory have described the experimental basis for our understanding of the genetic organization of the rosy locus (ry:3-52.0) of Drosophila melanogaster, as a bipartite genetic entity consisting of a structural element that codes for the xanthine dehydrogenase (XDH) peptide and a contiguous, cis-acting control element. The present report describes our progress in the analysis of the control element and its variants. Characterization of the control element variants reveals that, with respect to late third instar larval tissue distribution of XDH activity and cross-reacting material, i409H is associated with a large, tissue-specific increase in fat body which is not observed in malpighian tubules. Further data are presented in support of the inference that this differential expression must reflect differential production of XDH-specific RNA transcripts.—Gel blot analyses are described which demonstrate (1) that the phenotypic effects associated with variation in the rosy locus control element relate to differences in accumulation of XDH-specific poly-A+ RNA and (2) do not relate to differences in rosy DNA template numbers.—Experiments are described that provide for unambiguous mapping of control element sites through the use of half-tetrad recombination experiments and the recovery and phenotypic characterization of the reciprocal products of exchange between control element site variants. Thus, we are able to order the sites as follows: kar-i1005 i409-ry.

scholarly journals A Novel Method to Predict Drug-Target Interactions Based on Large-Scale Graph Representation Learning

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2111
Author(s):  
Bo-Wei Zhao ◽  
Zhu-Hong You ◽  
Lun Hu ◽  
Zhen-Hao Guo ◽  
Lei Wang ◽  
...  
Keyword(s):  
Drug Target ◽  
Large Scale ◽  
Computational Models ◽  
Structural Information ◽  
Characteristic Curve ◽  
Representation Learning ◽  
Graph Representation ◽  
Convolutional Network ◽  
Novel Method

Identification of drug-target interactions (DTIs) is a significant step in the drug discovery or repositioning process. Compared with the time-consuming and labor-intensive in vivo experimental methods, the computational models can provide high-quality DTI candidates in an instant. In this study, we propose a novel method called LGDTI to predict DTIs based on large-scale graph representation learning. LGDTI can capture the local and global structural information of the graph. Specifically, the first-order neighbor information of nodes can be aggregated by the graph convolutional network (GCN); on the other hand, the high-order neighbor information of nodes can be learned by the graph embedding method called DeepWalk. Finally, the two kinds of feature are fed into the random forest classifier to train and predict potential DTIs. The results show that our method obtained area under the receiver operating characteristic curve (AUROC) of 0.9455 and area under the precision-recall curve (AUPR) of 0.9491 under 5-fold cross-validation. Moreover, we compare the presented method with some existing state-of-the-art methods. These results imply that LGDTI can efficiently and robustly capture undiscovered DTIs. Moreover, the proposed model is expected to bring new inspiration and provide novel perspectives to relevant researchers.

scholarly journals A novel 7-nucleotide motif located in 3' untranslated sequences of the immediate-early gene set mediates platelet-derived growth factor induction of the JE gene.

1992 ◽  
Vol 12 (12) ◽  
pp. 5288-5300 ◽  
Author(s):  
R R Freter ◽  
J C Irminger ◽  
J A Porter ◽  
S D Jones ◽  
C D Stiles
Keyword(s):  
Growth Factor ◽  
Immediate Early Genes ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Platelet Derived Growth Factor ◽  
Immediate Early ◽  
Control Element ◽  
Gene Set ◽  
Cis Acting ◽  
Early Genes

A cohort of the serum and growth factor regulated immediate-early gene set is induced with slower kinetics than c-fos. Two of the first immediate-early genes characterized as such, c-myc and JE, are contained within this subset. cis-acting genomic elements mediating induction of the slower responding subset of immediate-early genes have never been characterized. Herein we characterize two widely separated genomic elements which are together essential for induction of the murine JE gene by platelet-derived growth factor, serum, interleukin-1, and double-stranded RNA. One of these elements is novel in several regards. It is a 7-mer, TTTTGTA, found in the proximal 3' sequences downstream of the JE stop codon. The 3' element is position dependent and orientation independent. It does not function in polyadenylation, splicing, or destabilization of the JE transcript. Copies of the 7-mer or its inverse are found at comparable 3' sites in 25 immediate-early genes that encode transcription factors or cytokines. Given its general occurrence, the 7-mer may be a required cis-acting control element mediating induction of the immediate-early gene set.

Efficient and High-Quality Seeded Graph Matching: Employing Higher-order Structural Information

2021 ◽  
Vol 15 (3) ◽  
pp. 1-31
Author(s):  
Haida Zhang ◽  
Zengfeng Huang ◽  
Xuemin Lin ◽  
Zhe Lin ◽  
Wenjie Zhang ◽  
...  
Keyword(s):  
Large Scale ◽  
Graph Matching ◽  
Structural Information ◽  
Experimental Studies ◽  
Higher Order ◽  
Personalized Pagerank ◽  
Matching Accuracy ◽  
Approximation Techniques ◽  
Order Of Magnitude ◽  
Matching Score

Driven by many real applications, we study the problem of seeded graph matching. Given two graphs and , and a small set of pre-matched node pairs where and , the problem is to identify a matching between and growing from , such that each pair in the matching corresponds to the same underlying entity. Recent studies on efficient and effective seeded graph matching have drawn a great deal of attention and many popular methods are largely based on exploring the similarity between local structures to identify matching pairs. While these recent techniques work provably well on random graphs, their accuracy is low over many real networks. In this work, we propose to utilize higher-order neighboring information to improve the matching accuracy and efficiency. As a result, a new framework of seeded graph matching is proposed, which employs Personalized PageRank (PPR) to quantify the matching score of each node pair. To further boost the matching accuracy, we propose a novel postponing strategy, which postpones the selection of pairs that have competitors with similar matching scores. We show that the postpone strategy indeed significantly improves the matching accuracy. To improve the scalability of matching large graphs, we also propose efficient approximation techniques based on algorithms for computing PPR heavy hitters. Our comprehensive experimental studies on large-scale real datasets demonstrate that, compared with state-of-the-art approaches, our framework not only increases the precision and recall both by a significant margin but also achieves speed-up up to more than one order of magnitude.

PSVIII-5 Genetic parameters of thrombin as a proxy for horn fly abundance in beef cattle

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 239-239
Author(s):  
Ashley S Ling ◽  
Taylor Krause ◽  
Amanda Warner ◽  
Jason Duggin ◽  
Bradley Heins ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Fixed Effects ◽  
Large Scale ◽  
Genetic Basis ◽  
Threshold Model ◽  
Economic Losses ◽  
Small Data ◽  
Horn Fly ◽  
Improvement Programs ◽  
Highest Posterior Density

Abstract Horn flies (Haematobia irritans) are a major nuisance to cattle, especially in warm, humid regions, and are estimated to cause economic losses in excess of $1 billion annually to the U.S. beef cattle industry. Variation in horn fly tolerance has been reported within and across breeds, and heritability estimates ranging between 10 and 80% show a clear genetic basis. However, collecting fly abundance phenotypes is costly and logistically demanding, which precludes large-scale implementation. Consequently, finding correlated phenotypes and endo-phenotypes that are heritable and relatively easy to measure would facilitate implementation of horn fly tolerance genetic improvement programs. Thrombin (TH), a blood coagulation precursor, has a reported association with horn fly count variation within and across cattle breeds. In this study, the genetic basis of thrombin in beef cattle was investigated. Blood samples and horn fly count were collected on 360 cows and heifers twice during the summer of 2019 (June and August). Due to uncertainty associated with assessment of horn fly abundance and thrombin and the fact that economic losses occur only when fly abundance exceeds a certain threshold, thrombin was categorized into 4 classes (1=TH > 500 ng/ml; 2=250< TH< 500 ng/ml; 3=100< TH< 250 ng/ml; and 4=TH< 100 ng/ml). The trait was analyzed using linear (continuous) and threshold (discrete) mixed models. Both models included farm, pregnancy status, and cow age as fixed effects and additive and permanent environment random effects. The pedigree included 642 animals. Estimates of heritability were 0.24 and 0.29 using linear and threshold models, respectively. Estimates of repeatability were slightly higher using the threshold model (0.21 vs 0.19). Despite the small data size, all estimates were non-zero based on their respective highest posterior density intervals. These results indicate reasonable genetic variation for thrombin that could be harnessed for improvement of horn fly tolerance in cattle.

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