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At least 1,225 records · Page 68Linked to original sources
PubMed2001

Genome-wide linkage scan to detect loci influencing levels of dehydroepiandrosterones in the HERITAGE Family Study.

A genome-wide linkage scan was performed to identify genomic regions that influence levels of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and DHEA fatty acid esters (DHEA-FA) at baseline and in response to 20 weeks of endurance exercise training in sedentary white and black participants in the HERITAGE Family Study. The baseline levels were log-transformed and adjusted for the effects of age and sex prior to genetic analysis. The training responses were adjusted for the effects of age, sex, and the baseline values. A total of 509 autosomal component polymorphic markers were used for the genome scan with an average spacing of 6.0 Mb. Multipoint variance components linkage analyses were performed in nuclear families containing 360 white and 106 black sibling pairs. We found 5 genomic regions with significant linkages for baseline DHEA-FA in whites, with log odd (LOD) scores over 3.6 (P < 2 x 10(-5)). They include (1) D1S468 (LOD 4.56, 2.533 Mb, 1p36.22); (2) D2S177 (LOD 5.65, 52.663 Mb, 2p16.3); (3) D4S2397 (LOD 3.98, 32.246 Mb, 4p15.2); (4) the paraoxonase loci (LOD 3.93 approximately 3.99, 101.544 approximately 102.933 Mb, 7q21.3), and D7S821 (LOD 3.88, 104.497 Mb, 7q22.1); and (5) D12S372 (LOD 4.66, 2.129 Mb, 12q13.33). In addition, we obtained evidence of suggestive linkages (2.2 < LOD < 3.6; 2 x 10(-5) < P < 7 x 10(-4)) on chromosomes 3p, 6q, and 8q for baseline DHEAS; on chromosomes 2q, 3p, 9q, 10p, 16q, and 17p for baseline DHEA-FA in whites; and on chromosomes 9q and 11p for baseline DHEA in blacks. This is the first genome-wide linkage scan searching for genomic regions influencing human DHEA levels. Several potential candidate genes are located in these genomic regions, which warrant further studies in HERITAGE and other cohorts.

Adult↗
PubMed2026

Genome-wide scans reveal candidate genes associated with wing morph differentiation in Tetrix japonica.

Wing dimorphism is an important dispersal-related trait in insects, but its genomic basis remains poorly understood in pygmy grasshoppers. Here, we integrated genome-wide single-nucleotide polymorphism (SNP) analyses, population structure inference, selection scans, and functional annotation to investigate genomic differentiation between long- and short-winged Tetrix japonica. Principal component analysis (PCA), ADMIXTURE, and phylogenetic analyses revealed weak genome-wide separation between morphs, indicating differentiation on a largely shared genetic background. Genome-wide scans based on the fixation index (FST), nucleotide diversity ratios, and Tajima's D, using 50-kb non-overlapping windows and empirical top-5% outlier thresholds, identified multiple candidate regions across seven chromosomes. The broader long- and short-winged candidate sets spanned 9.35&#xa0;Mb and 9.37&#xa0;Mb and directly overlapped 82 and 77 genes, respectively. Candidate genes were associated with signaling/hormone regulation, membrane transport, metabolism, cytoskeletal organization, extracellular matrix structure, and development. Short-winged candidate genes were significantly enriched for ABC-type transporter activity and ATP hydrolysis activity. Because all individuals originated from a single laboratory-maintained population with weak genome-wide structure, these regions should be regarded as candidate loci from a screening-stage analysis that require validation in independent populations and by functional assays, rather than as confirmed targets of selection.

Animals↗
PubMed2005

Prediction of functional modules based on gene distributions in microbial genomes.

We present a computational method for prediction of functional modules that can be directly applied to the newly sequenced microbial genomes for predicting gene functions and the component genes of biological pathways. We first quantify the functional relatedness among genes based on their distribution (i.e., their existences and orders) across multiple microbial genomes, and obtain a gene network in which every pair of genes is associated with a score representing their functional relatedness. We then apply a threshold-based clustering algorithm to this gene network, and obtain modules for each of which the number of genes is bounded from above by a pre-specified value and the component genes are more strongly functionally related to each other than genes across the predicted modules. Particularly, when the module size is bounded by 130, we obtain 167 functional modules covering 813 genes for Escherichia coli K12, and 138 functional modules covering 731 genes for Bacillus subtilis subsp. subtilis str. 168. We have used the gene ontology (GO) information to assess the prediction results. The GO similarities among the genes of the same functional module are compared with the GO similarities among the genes that are randomly clustered together. This comparison reveals that our predicted functional modules are statistically and biologically significant, and the genes of the same functional module share more commonality in terms of biological process than in terms of molecular function or cellular component. We have also examined the predicted functional modules that are common to both Escherichia coli K12 and Bacillus subtilis subsp. subtilis str. 168, and provide explanations for some functional modules.

Cluster Analysis↗
PubMed2006

Global identification of noncoding RNAs in Saccharomyces cerevisiae by modulating an essential RNA processing pathway.

Noncoding RNAs (ncRNAs) perform essential cellular tasks and play key regulatory roles in all organisms. Although several new ncRNAs in yeast were recently discovered by individual studies, to our knowledge no comprehensive empirical search has been conducted. We demonstrate a powerful and versatile method for global identification of previously undescribed ncRNAs by modulating an essential RNA processing pathway through the depletion of a key ribonucleoprotein enzyme component, and monitoring differential transcriptional activities with genome tiling arrays during the time course of the ribonucleoprotein depletion. The entire Saccharomyces cerevisiae genome was scanned during cell growth decay regulated by promoter-mediated depletion of Rpp1, an essential and functionally conserved protein component of the RNase P enzyme. In addition to most verified genes and ncRNAs, expression was detected in 98 antisense and intergenic regions, 74 that were further confirmed to contain previously undescribed RNAs. A class of ncRNAs, located antisense to coding regions of verified protein-coding genes, is discussed in this article. One member, HRA1, is likely involved in 18S rRNA maturation.

Base Sequence↗
PubMed2005

Aspergillus nidulans HOG pathway is activated only by two-component signalling pathway in response to osmotic stress.

Genome sequencing analyses revealed that Aspergillus nidulans has orthologous genes to all those of the high-osmolarity glycerol (HOG) response mitogen-activated protein kinase (MAPK) pathway of Saccharomyces cerevisiae. A. nidulans mutant strains lacking sskA, sskB, pbsB, or hogA, encoding proteins orthologous to the yeast Ssk1p response regulator, Ssk2p/Ssk22p MAPKKKs, Pbs2p MAPKK and Hog1p MAPK, respectively, showed growth inhibition under high osmolarity, and HogA MAPK in these mutants was not phosphorylated under osmotic or oxidative stress. Thus, activation of the A. nidulans HOG (AnHOG) pathway depends solely on the two-component signalling system, and MAPKK activation mechanisms in the AnHOG pathway differ from those in the yeast HOG pathway, where Pbs2p is activated by two branches, Sln1p and Sho1p. Expression of pbsB complemented the high-osmolarity sensitivity of yeast pbs2Delta, and the complementation depended on Ssk2p/Ssk22p, but not on Sho1p. Pbs2p requires its Pro-rich motif for binding to the Src-homology3 (SH3) domain of Sho1p, but PbsB lacks a typical Pro-rich motif. However, a PbsB mutant (PbsB(Pro)) with the yeast Pro-rich motif was activated by the Sho1p branch in yeast. In contrast, HogA in sskADelta expressing PbsB(Pro) was not phosphorylated under osmotic stress, suggesting that A. nidulans ShoA, orthologous to yeast Sho1p, is not involved in osmoresponsive activation of the AnHOG pathway. We also found that besides HogA, PbsB can activate another Hog1p MAPK orthologue, MpkC, in A. nidulans, although mpkC is dispensable in osmoadaptation. In this study, we discuss the differences between the AnHOG and the yeast HOG pathways.

Amino Acid Motifs↗
PubMed1989

Functional expression of the leftward open reading frames of the A component of tomato golden mosaic virus in transgenic tobacco plants.

The genome of the geminivirus tomato golden mosaic virus (TGMV) consists of two circular DNA molecules designated as components A and B. We have constructed Nicotiana benthamiana plants that are transgenic for the three overlapping open reading frames, AL1, AL2, and AL3, from the left side of TGMV A. In the transgenic plants, the AL open reading frames are under the control of the cauliflower mosaic virus (CaMV) 35S promoter. In TGMV infectivity assays, seven of 10 transgenic lines complemented TGMV A variants with mutations in AL1, AL2, or AL3 when co-inoculated with the B component. The 35S-AL construct was transcribed as a single RNA species in the transgenic plants, indicating that AL1, AL2, and AL3 were expressed from a polycistronic mRNA. This differs from the complex transcription pattern in TGMV-infected plants, which contains five AL transcripts. There was no quantitative correlation between the efficiency of complementation in the infectivity assay and the level of expression of transgenic AL RNA in the leaves of a transgenic line. One line that failed to complement defects in AL1, AL2, and AL3 in infectivity assays contained high levels of transgenic AL RNA and functional AL1 protein. These results provide evidence that chromosomal position can affect the cell- and tissue-specific transcription of the 35S promoter in transgenic plants. Comparison of the complementing plants and wild-type infected plants may provide insight into the TGMV infection process and the use of the CaMV 35S promoter for gene expression in transgenic plants.

Base Sequence↗
PubMed1982

The genome of Schistosoma mansoni: isolation of DNA, its size, bases and repetitive sequences.

DNA has been prepared from adults and cercariae of Schistosoma mansoni utilizing a technique that involves centrifugation through cesium chloride. The DNA isolated from S. mansoni adults and that isolated from cercariae were found to be indistinguishable in all analyses. No modified bases were detected by chromatography or comparative endonuclease restriction. Cot analysis demonstrated that the haploid genome of S. mansoni is 0.26 pg (2.7 X 10(8) base pairs) and that the genome contains both moderately and highly repeated components. Some of the repetitive fraction of DNA consists of tandemly repeated ribosomal genes of which there are 500-1000 copies per genome (1.8-3.6% of the total DNA). Four other non-ribosomal repetitive sequences (comprising at least a further 2.0% of the total DNA) have been isolated from a DNA clone bank and their arrangement within the S. mansoni genome investigated by restriction and Southern blot analysis. These cloned segments of DNA appear in many different locations within the genome and thus are reminiscent of the interspersed DNA sequences described in higher eukaryotic organisms.

Animals↗
PubMed1990

Discoordinate expression of the yeast mitochondrial ribosomal protein MRP1.

We have examined expression of the protein coded within the MRP 1 locus of Saccharomyces cerevisiae. Direct evidence is provided for the assignment of the MRP1 gene product as a protein component of the small subunit of mitochondrial ribosomes. Further studies examined the extent to which the expression of the MRP1 protein is coordinated with the expression of other mitochondrial ribosomal components coded in the nuclear and mitochondrial genomes. Extra copies of the MRP1 gene were introduced into yeast cells to perturb expression from MRP1 relative to other mitochondrial ribosomal components to determine whether forms of regulation function to limit the accumulation of either MRP1 mRNA or protein under these conditions. Increases in MRP1 gene dosage were accompanied by substantial increases in both MRP1 mRNA and protein, indicating that their accumulation was not linked to the level of expression of other mitochondrial ribosomal components. This conclusion was confirmed by additional studies that showed that the accumulation of the MRP1 protein was unaffected in cells that did not express mitochondrially-encoded rRNAs. These results contrast with previous studies on the expression of two other mitochondrial ribosomal proteins indicating that regulatory properties of mitochondrial ribosomal proteins are quite diverse.

Genes, Fungal↗
PubMed2026

Comparative analysis of conserved non-coding elements identifies gene regulatory networks rewired during the water-to-land transition in vertebrates.

The conquest of land by vertebrates has been a pivotal moment in evolutionary history. Adapting to the new habitats necessitated numerous changes in vertebrate anatomy and physiology, creating an enduring imprint on the developmental gene regulatory networks (GRNs) of tetrapods. The increase of high-quality genomic resources over the past decade has made it possible to study the genomic legacy of the water-to-land transition. While much attention has been given to the highly conserved non-coding elements (CNEs) of the genome that share high levels of similarity across evolutionarily diverged clades, recent evidence suggests that perhaps comparable attention should be given to "missing" CNE-s, conserved sequence patches present in extant stem gnathostomes and actinopterygian fishes that have become undetectable in tetrapods during the adaptation to terrestrial life, whether through true sequence loss or divergence beyond alignability. These sequences could help us reveal the relaxation of certain developmental constraints, related to the aquatic lifestyle, that made reaching new adaptive peaks in the developmental landscape possible. In this paper, we search for such CNEs and characterize them in comparison with pan-Gnathostome CNEs, using the zebrafish (Danio rerio) genome as a reference. Our results suggest that the rewiring of developmental networks related to pigmentation and muscle structure formation has left the largest genomic imprint. We also find that components of canonical Wnt and Hedgehog signalling, are enriched among CNEs retained in fish.

cis-regulatory evolution↗
PubMed1985

The alpha sequence of the cytomegalovirus genome functions as a cleavage/packaging signal for herpes simplex virus defective genomes.

Although herpes simplex virus (HSV) 1 and human cytomegalovirus (CMV) differ remarkably in their biological characteristics and do not share nucleotide sequence homology, they have in common a genome structure that undergoes sequence isomerization of the long (L) and short (S) components. We have demonstrated that the similarity in their genome structures extends to the existence of an alpha sequence in the CMV genome as previously defined for the HSV genome. As such, the alpha sequence is predicted to participate as a cis-replication signal in four viral functions: (i) inversion, (ii) circularization, (iii) amplification, and (iv) cleavage and packaging of progeny viral DNA. We have constructed a chimeric HSV-CMV amplicon (herpesvirus cis replication functions carried on an Escherichia coli plasmid vector) substituting CMV DNA sequences for the HSV cleavage/packaging signal in a test of the ability of this CMV L-S junction sequence to provide the cis signal for cleavage/packaging in HSV 1-infected cells. We demonstrate that the alpha sequence of CMV DNA functions as a cleavage/packaging signal for HSV defective genomes. We show the structure of this sequence and provide a functional demonstration of cross complementation in replication signals which have been preserved over evolutionary time in these two widely divergent human herpesviruses.

Animals↗
PubMed1998

Parameters of the chicken genome (Gallus gallus).

As more information on the chicken genome is gathered, it is becoming increasingly more important to be able to correlate genetic and physical maps. Quantitation of the chicken karyotype is important in establishing parameters which define the genome. Here we report on the physical lengths of the chicken macrochromosomes and establish the DNA content of each, thus identifying implicitly how much of the genome is represented by the microchromosomal component. For the first time, genetic and physical data on the chicken karyotype are presented in relation to one another.

Animals↗
PubMed1996

Mitochondrial DNA polymerase gamma is expressed and translated in the absence of mitochondrial DNA maintenance and replication.

Mitochondria are essential organelles in all eukaryotic cells where cellular ATP is generated through the process of oxidative phosphorylation. Protein components of the respiratory assembly are gene products of both mitochondrial and nuclear genes. The mitochondrial genome itself encodes several protein and nucleic acid components required for such oxidative phosphorylative processes, but the vast majority of genes encoding respiratory chain components are nuclear. Similarly, the processes of replication and transcription of mitochondrial DNA rely exclusively upon RNA and protein species encoded by nuclear genes. We have analyzed two key nuclear-encoded proteins involved in mitochondrial DNA replication and transcription as a function of the presence or absence of mitochondrial DNA. Mitochondrial DNA polymerase (DNA polymerase gamma), the nuclear-encoded enzyme which synthesizes mtDNA, is expressed and translated in cells devoid of mitochondrial DNA itself. In contrast, mitochondrial transcription factor A protein levels are tightly linked to the mtDNA status of the cell. These results demonstrate that the DNA polymerase gamma protein is stable in the absence of mitochondrial DNA, and that there appears to be no regulatory mechanism present in these cells to alter levels of this protein in the complete absence of mitochondrial DNA. Alternatively, it is possible that this enzyme plays an additional, as yet undefined, role in the cell, thereby mandating its continued production.

Base Sequence↗
PubMed1998

BioViews: Java-based tools for genomic data visualization.

Visualization tools for bioinformatics ideally should provide universal access to the most current data in an interactive and intuitive graphical user interface. Since the introduction of Java, a language designed for distributed programming over the Web, the technology now exists to build a genomic data visualization tool that meets these requirements. Using Java we have developed a prototype genome browser applet (BioViews) that incorporates a three-level graphical view of genomic data: a physical map, an annotated sequence map, and a DNA sequence display. Annotated biological features are displayed on the physical and sequence-based maps, and the different views are interconnected. The applet is linked to several databases and can retrieve features and display hyperlinked textual data on selected features. In addition to browsing genomic data, different types of analyses can be performed interactively and the results of these analyses visualized alongside prior annotations. Our genome browser is built on top of extensible, reusable graphic components specifically designed for bioinformatics. Other groups can (and do) reuse this work in various ways. Genome centers can reuse large parts of the genome browser with minor modifications, bioinformatics groups working on sequence analysis can reuse components to build front ends for analysis programs, and biology laboratories can reuse components to publish results as dynamic Web documents.

Animals↗
PubMed2006

Predicting survival within the lung cancer histopathological hierarchy using a multi-scale genomic model of development.

BACKGROUND: The histopathologic heterogeneity of lung cancer remains a significant confounding factor in its diagnosis and prognosis-spurring numerous recent efforts to find a molecular classification of the disease that has clinical relevance. METHODS AND FINDINGS: Molecular profiles of tumors from 186 patients representing four different lung cancer subtypes (and 17 normal lung tissue samples) were compared with a mouse lung development model using principal component analysis in both temporal and genomic domains. An algorithm for the classification of lung cancers using a multi-scale developmental framework was developed. Kaplan-Meier survival analysis was conducted for lung adenocarcinoma patient subgroups identified via their developmental association. We found multi-scale genomic similarities between four human lung cancer subtypes and the developing mouse lung that are prognostically meaningful. Significant association was observed between the localization of human lung cancer cases along the principal mouse lung development trajectory and the corresponding patient survival rate at three distinct levels of classical histopathologic resolution: among different lung cancer subtypes, among patients within the adenocarcinoma subtype, and within the stage I adenocarcinoma subclass. The earlier the genomic association between a human tumor profile and the mouse lung development sequence, the poorer the patient's prognosis. Furthermore, decomposing this principal lung development trajectory identified a gene set that was significantly enriched for pyrimidine metabolism and cell-adhesion functions specific to lung development and oncogenesis. CONCLUSIONS: From a multi-scale disease modeling perspective, the molecular dynamics of murine lung development provide an effective framework that is not only data driven but also informed by the biology of development for elucidating the mechanisms of human lung cancer biology and its clinical outcome.

Adenocarcinoma↗
PubMed2005

Telomere instability in the male germline.

Telomeres play a key role in upholding the integrity of the genome, and telomerase expression in spermatogonial stem cells is responsible for the maintenance of telomere length in the human male germline. We have previously described extensive allelic variation in somatic cell telomere length that is set in the zygote, the ultimate source of which may be the germline. This implies that despite telomerase activity, substantial telomere length variation can be generated and tolerated in the germline; in order to investigate this further, we have examined the nature of telomere length variation in the human male germline. Here, we describe an analysis of both genome-wide telomere length and single molecule analysis of specific chromosome ends in human sperm. We observed individual specific differences in genome-wide telomere length. This variation may result from genetic differences within the components that determine the telomere length setting of each individual. Superimposed on the genome wide telomere length setting was a stochastic component of variation that generates germ-cells containing severely truncated telomeres. If not re-lengthened during early embryogenesis, such telomeres may limit the replicative capacity of cells derived from the zygote and have the potential to create fusagenic chromosomes, unbalanced translocations and terminal micro-deletions. These data may have implications for the genetic determination of ageing, genetic disease and fertility.

Age Factors↗
PubMed1990

OP-1 cDNA encodes an osteogenic protein in the TGF-beta family.

Amino acid sequences of two tryptic peptides derived from enriched bovine osteogenic protein preparations revealed considerable homology to two members of the TGF-beta (transforming growth factor beta) supergene family, DPP (decapentaplegic protein) of Drosophila and Vg-1 (vegetal protein) of Xenopus. Building upon this information we constructed a synthetic consensus gene to use as a probe to screen human genomic libraries. This resulted in the isolation of three interrelated genes. Among these were BMP-2b and BMP-3 which have recently been described by others. The third gene, termed OP-1 (osteogenic protein one), is new and was subsequently shown to encode the human homolog of a major component of bovine osteogenic protein. The genomic clones were used to isolate the corresponding complementary DNA (cDNA) clones. Sequence analysis indicates that OP-1 is a relative of the murine Vgr-1 (Vg-1 related gene). This report describes the cDNA structure and putative amino acid sequence of OP-1.

Amino Acid Sequence↗
PubMed1999

Amplification and cloning of infectious bursal disease virus genomic RNA segments by long and accurate PCR.

Improved methods of reverse transcription, polymerase chain reaction (PCR) amplification, and cloning of full-length coding region of both strands of infectious bursal disease virus (IBDV) variant strain E genome were developed. Denaturation of IBDV RNA by heat in the presence of primers and use of a reverse transcriptase lacking RNase-H activity produced full-length coding region and partial non-coding region cDNA copies of the viral genomic segments. Digestion of the RNA component of RNA-cDNA hybrids by RNase-H followed by long and accurate PCR (LA-PCR) amplification of IBDV cDNA in a single step resulted in the synthesis of 3182 base-pairs (bp) of segment A and 2777 bp of segment B cDNA copies of IBDV genome. The resulting amplicons were successfully cloned and sequenced revealing their identity of IBDV. The LA-PCR method can be utilized for the amplification and cloning of the other IBDV strains or isolates and will greatly enhance the availability of sequence information or infectious cDNA copies of IBDV.

Animals↗
PubMed2006

Weight-adjusted genome scan analysis for mapping quantitative trait Loci for menarchal age.

CONTEXT: Twin and family studies indicate that genetic factors contribute to the variability of age at menarche (AAM), a multifactorial trait of major importance to human reproductive success. Individual variability of premenarcheal fatness is known to be an important determinant of AAM. OBJECTIVE: The objective of the study was mapping quantitative trait loci (QTLs) for AAM. DESIGN AND METHODS: AAM was assessed in 98 sister pairs of recent European ancestry whose growth charts were available. There was a negative correlation between menarcheal body weight sd score (SDS) and AAM (r = 0.47, P < 0.0001). We designed a genome scan approach and used the variance components model implemented in Merlin for quantitative traits to evaluate linkage of AAM and AAM adjusted for menarcheal weight SDS to 418 genome-wide microsatellites. RESULTS: Multipoint linkage analysis for AAM revealed nominal QTLs defined by LOD scores between 1.06 and 1.69 on chromosomes 1p, 1q, 7p, 8q, 16p, 19q, and 20q. The genome scan for AAM adjusted for menarcheal weight SDS revealed several QTLs with strongly suggestive LOD scores in 16q21 (LOD = 3.33), 16q12 (LOD = 3.12), and 8p12 (LOD = 2.18) and a number of other nominally significant QTLs yet viewed as hypothetical. CONCLUSIONS: We found several regions that may contain determinants of AAM, but there is still a long series of steps to confirm these QTLs and identify the genomic polymorphisms implicated in AAM variability.

Age Factors↗