Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “gene function”

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 901 records · Page 50Linked to original sources
PubMed2006

Duplication and relocation of the functional DPY19L2 gene within low copy repeats.

BACKGROUND: Low copy repeats (LCRs) are thought to play an important role in recent gene evolution, especially when they facilitate gene duplications. Duplicate genes are fundamental to adaptive evolution, providing substrates for the development of new or shared gene functions. Moreover, silencing of duplicate genes can have an indirect effect on adaptive evolution by causing genomic relocation of functional genes. These changes are theorized to have been a major factor in speciation. RESULTS: Here we present a novel example showing functional gene relocation within a LCR. We characterize the genomic structure and gene content of eight related LCRs on human Chromosomes 7 and 12. Two members of a novel transmembrane gene family, DPY19L, were identified in these regions, along with six transcribed pseudogenes. One of these genes, DPY19L2, is found on Chromosome 12 and is not syntenic with its mouse orthologue. Instead, the human locus syntenic to mouse Dpy19l2 contains a pseudogene, DPY19L2P1. This indicates that the ancestral copy of this gene has been silenced, while the descendant copy has remained active. Thus, the functional copy of this gene has been relocated to a new genomic locus. We then describe the expansion and evolution of the DPY19L gene family from a single gene found in invertebrate animals. Ancient duplications have led to multiple homologues in different lineages, with three in fish, frogs and birds and four in mammals. CONCLUSION: Our results show that the DPY19L family has expanded throughout the vertebrate lineage and has undergone recent primate-specific evolution within LCRs.

Amino Acid Sequence↗
PubMed1989

A recessive tumor gene function in Drosophila is involved in cell adhesion.

The phenotypic effects of lethal (2) giant larvae mutations are due to unstructured growth of brain and imaginal disc cells in homozygous mutant larvae. Molecular properties of the wildtype l (2) gl protein and its tissue specificity of expression suggest that the protein is required for the adhesion of cells which are about the stop cell division and undergo terminal differentiation.

Animals↗
PubMed1998

The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations.

The Saccharomyces cerevisiae genome encodes four MutL homologs. Of these, MLH1 and PMS1 are known to act in the MSH2-dependent pathway that repairs DNA mismatches. We have investigated the role of MLH3 in mismatch repair. Mutations in MLH3 increased the rate of reversion of the hom3-10 allele by increasing the rate of deletion of a single T in a run of 7 Ts. Combination of mutations in MLH3 and MSH6 caused a synergistic increase in the hom3-10 reversion rate, whereas the hom3-10 reversion rate in an mlh3 msh3 double mutant was the same as in the respective single mutants. Similar results were observed when the accumulation of mutations at frameshift hot spots in the LYS2 gene was analyzed, although mutation of MLH3 did not cause the same extent of affect at every LYS2 frameshift hot spot. MLH3 interacted with MLH1 in a two-hybrid system. These data are consistent with the idea that a proportion of the repair of specific insertion/deletion mispairs by the MSH3-dependent mismatch repair pathway uses a heterodimeric MLH1-MLH3 complex in place of the MLH1-PMS1 complex.

Base Sequence↗
PubMed1995

Complementation of African cassava mosaic virus AC2 gene function in a mixed bipartite geminivirus infection.

We have previously demonstrated that African cassava mosaic virus (ACMV) DNAs A and B efficiently complement the systemic spread of tomato golden mosaic virus (TGMV) DNA A when co-agroinoculated onto Nicotiana benthamiana. Here, we show that a mixture of an ACMV DNA A AC2 mutant and DNA B that is normally unable to systemically infect N. benthamiana can do so at low frequency when co-agroinoculated with TGMV DNA A. Analysis of viral DNA showed that the AC2 mutation was retained during infection. The mixture of genomic components was sap transmissible, indicating that systemic infectivity is not specifically attributable to the use of agroinoculation. In the presence of TGMV DNA A, ACMV coat protein as well as the DNA B gene products BV1 and BC1 were detected in systemically infected tissues. The results demonstrate that dysfunctional AC2 can be complemented in planta by its TGMV homologue AL2.

Africa↗
PubMed1992

Regulatory sequences clustered at the 5' end of the first intron of the human thymidylate synthase gene function in cooperation with the promoter region.

A human thymidylate synthase (TS) minigene containing 5'- and 3'-flanking sequences, all the exons, and only intron 1 showed a normal frequency of stable transformation when transfected into TS-negative mutant cells, whereas minigenes in which intron 1 was replaced by intron 2 or deleted in the above construct showed only a few percent of the above frequency. Introduction of intron 1 into the above intronless or intron 2 minigene restored the transforming activities regardless of its position and orientation. Deletion analysis revealed two positive and one negative regulatory sequences in the 5' end of intron 1, each of which seemed to bind specific proteins as shown by gel shift analysis. Intron 1 also stimulated expression of a TS promoter-CAT gene construct but not that of an SV40 promoter-CAT gene construct. These results indicate that the multiple regulatory sequences clustered in intron 1 stimulate TS gene expression in concert with the 5'-flanking sequences.

Gene Expression Regulation, Enzymologic↗
PubMed2003

Predicting gene function in Saccharomyces cerevisiae.

MOTIVATION: S.cerevisiae is one of the most important model organisms, and has has been the focus of over a century of study. In spite of these efforts, 40% of its open reading frames (ORFs) remain classified as having unknown function (MIPS: Munich Information Center for Protein Sequences). We wished to make predictions for the function of these ORFs using data mining, as we have previously successfully done for the genomes of M.tuberculosis and E.coli. Applying this approach to the larger and eukaryotic S.cerevisiae genome involves modifying the machine learning and data mining algorithms, as this is a larger organism with more data available, and a more challenging functional classification. RESULTS: Novel extensions to the machine learning and data mining algorithms have been devised in order to deal with the challenges. Accurate rules have been learned and predictions have been made for many of the ORFs whose function is currently unknown. The rules are informative, agree with known biology and allow for scientific discovery. AVAILABILITY: All predictions are freely available from http://www.genepredictions.org, all datasets used in this study are freely available from http://www.aber.ac.uk/compsci/Research/bio/dss/yeastdataand software for relational data mining is available from http://www.aber.ac.uk/compsci/Research/bio/dss/polyfarm.

Chromosome Mapping↗
PubMed2004

Assaying gene function by growth competition experiment.

High-throughput screening and analysis is one of the emerging paradigms in biotechnology. In particular, high-throughput methods are essential in the field of functional genomics because of the vast amount of data generated in recent and ongoing genome sequencing efforts. In this report we discuss integrated functional analysis methodologies which incorporate both a growth competition component and a highly parallel assay used to quantify results of the growth competition. Several applications of the two most widely used technologies in the field, i.e., transposon mutagenesis and deletion strain library growth competition, and individual applications of several developing or less widely reported technologies are presented.

Animals↗
PubMed1995

The relationship between mRNA half-life and gene function in the yeast Saccharomyces cerevisiae.

Saccharomyces cerevisiae (Sc) mRNAs have been described as falling into two major classes with respect to mRNA half-life [Santiago et al., Nucleic Acids Res. 14 (1986) 8347-8360]. We have used DNA sequence analysis to address the functional roles of eleven of the thirteen cDNAs upon which Santiago et al. based their conclusions. Eight had been described as copies of short half-life and five as copies of long-half-life mRNAs. We show here that five members of the short-half-life class encode known Sc cytosolic ribosomal proteins (rp). One further short-half-life cDNA appears to encode a new Sc rp related to higher eukaryotic rp S12. Among the long-half-life cDNAs, one encodes the glucose-inducible glycolytic enzyme enolase, while another is related to the mouse housekeeping gene MER5.

Animals↗
PubMed1968

Assay systems for the study of gene function. 2 assay systems, the syntheses of RNA and protein, are described; their virtues and drawbacks are discussed.

The study of genetic regulatory mechanisms operating in plants and animals is of paramount importance in contemporary biology. A precise understanding of the mechanisms that underlie normal cellular differentiation is a prerequisite for understanding neoplastic transformation and genetic disease. At present, we are not aware of a single assay system that can give answers to all questions we are already able to pose. Studies of RNA synthesis are valuable because they provide a direct measurement of transcriptional activity. But these studies remain incomplete until we succeed in unraveling the metabolic roles of the molecules whose synthesis we study. In this respect, the study of enzyme synthesis represents a better defined assay system, although the interpretation of observed fluctuations in synthetic rates is made difficult by the many steps that intervene between the genes and their finished protein products. We propose that a combination of protein biosynthetic and cytogenetic analysis is a promising assay system for further investigation.

Alcohol Oxidoreductases↗
PubMed2006

Plasticity of the gene functions for DNA replication in the T4-like phages.

We have completely sequenced and annotated the genomes of several relatives of the bacteriophage T4, including three coliphages (RB43, RB49 and RB69), three Aeromonas salmonicida phages (44RR2.8t, 25 and 31) and one Aeromonas hydrophila phage (Aeh1). In addition, we have partially sequenced and annotated the T4-like genomes of coliphage RB16 (a close relative of RB43), A. salmonicida phage 65, Acinetobacter johnsonii phage 133 and Vibrio natriegens phage nt-1. Each of these phage genomes exhibited a unique sequence that distinguished it from its relatives, although there were examples of genomes that are very similar to each other. As a group the phages compared here diverge from one another by several criteria, including (a) host range, (b) genome size in the range between approximately 160 kb and approximately 250 kb, (c) content and genetic organization of their T4-like genes for DNA metabolism, (d) mutational drift of the predicted T4-like gene products and their regulatory sites and (e) content of open-reading frames that have no counterparts in T4 or other known organisms (novel ORFs). We have observed a number of DNA rearrangements of the T4 genome type, some exhibiting proximity to putative homing endonuclease genes. Also, we cite and discuss examples of sequence divergence in the predicted sites for protein-protein and protein-nucleic acid interactions of homologues of the T4 DNA replication proteins, with emphasis on the diversity in sequence, molecular form and regulation of the phage-encoded DNA polymerase, gp43. Five of the sequenced phage genomes are predicted to encode split forms of this polymerase. Our studies suggest that the modular construction and plasticity of the T4 genome type and several of its replication proteins may offer resilience to mutation, including DNA rearrangements, and facilitate the adaptation of T4-like phages to different bacterial hosts in nature.

Amino Acid Sequence↗
PubMed2005

Cell microarrays and RNA interference chip away at gene function.

The recent development of cell microarrays offers the potential to accelerate high-throughput functional genetic studies. The widespread use of RNA interference (RNAi) has prompted several groups to fabricate RNAi cell microarrays that make possible discrete, in-parallel transfection with thousands of RNAi reagents on a microarray slide. Though still a budding technology, RNAi cell microarrays promise to increase the efficiency, economy and ease of genome-wide RNAi screens in metazoan cells.

Animals↗
PubMed2006

The rice SPINDLY gene functions as a negative regulator of gibberellin signaling by controlling the suppressive function of the DELLA protein, SLR1, and modulating brassinosteroid synthesis.

SPINDLY (SPY) encodes an O-linked N-acetylglucosamine transferase that is considered to be a negative regulator of gibberellin (GA) signaling through an unknown mechanism. To understand the function of SPY in GA signaling in rice, we isolated a rice SPINDLY homolog (OsSPY) and produced knockdown transgenic plants in which OsSPY expression was reduced by introducing its antisense or RNAi construct. In knockdown plants, the enhanced elongation of lower internodes was correlated with decreased levels of OsSPY expression, similar to the spindly phenotype of Arabidopsis spy mutants, suggesting that OsSPY also functions as a negative factor in GA signaling in rice. The suppressive function of OsSPY in GA signaling was supported by the findings that the dwarfism was partially rescued and OsGA20ox2 (GA20 oxidase) expression was reduced in GA-deficient and GA-insensitive mutants by the knockdown of OsSPY function. The suppression of OsSPY function in a GA-insensitive mutant, gid2, also caused an increase in the phosphorylation of a rice DELLA protein, SLR1, but did not change the amount of SLR1. This indicates that the function of OsSPY in GA signaling is not via changes in the amount or stability of SLR1, but probably involves control of the suppressive function of SLR1. In addition to the GA-related phenotypes, OsSPY antisense and RNAi plants showed increased lamina joint bending, which is a brassinosteroid-related phenotype, indicating that OsSPY may play roles both in GA signaling and in the brassinosteroid pathway.

Amino Acid Sequence↗
PubMed1997

Mouse embryos in culture: models for understanding diabetes-induced embryopathies and gene function.

Both the metabolic studies on diabetes and the genetic studies using antisense oligodeoxynucleotides clearly demonstrate the importance and usefulness of rodent whole embryo culture. Without this technique, these studies would be impossible and, consequently, our knowledge of both normal and abnormal development would not be as advanced as it is today. The culture system fills a unique niche in studies in the fields of developmental biology and teratology and these sciences would have been less well served without Dr. New's contribution.

3-Hydroxybutyric Acid↗
PubMed2001

A computational neural approach to support the discovery of gene function and classes of cancer.

Advances in molecular classification of tumours may play a central role in cancer treatment. Here, a novel approach to genome expression pattern interpretation is described and applied to the recognition of B-cell malignancies as a test set. Using cDNA microarrays data generated by a previous study, a neural network model known as simplified fuzzy ARTMAP is able to identify normal and diffuse large B-cell lymphoma (DLBCL) patients. Furthermore, it discovers the distinction between patients with molecularly distinct forms of DLBCL without previous knowledge of those subtypes.

Algorithms↗
PubMed1976

Analysis of gene function of bacteriophage phi 29 of Bacillus subtilis: identification of cistrons essential for viral assembly.

Restrictive infection of Bacillus subtilis by suppressor-sensitive (sus) mutants of phi 29 has been used to search for cistrons that function in viral assembly. The products of cistrons 7, 9, 10, and 16 are necessary for head morphogenesis. The neck upper collar protein P10 and the tail protein P9 must be present for DNA packaging to occur. The protein P7 must be present for phage-related particles to form. A prohead-like particle has been isolated during 16-restrictive infection. The particle is composed of the proteins Hd, P10, F, and P7. P16 must function for DNA-filled particles to accumulate. A DNA-containing particle produced in the absence of the cistron 11 product may be an intermediate in the phi 29 assembly pathway. The protein P13 interacts with P9 and P11 to form a stable DNA-filled particle. The products of cistrons 2 and 3 are essential for viral DNA synthesis, and in their absence virus-related particles are not detected.

Bacillus subtilis↗
PubMed1998

Follicular cells of the thyroid gland require Pax8 gene function.

The thyroid gland develops from two distinct embryonic lineages: follicular cells (which produce thyroxine) and parafollicular C-cells (which produce calcitonin) are of endodermal and neural crest origin, respectively. Little is known about the molecular mechanisms governing the generation of these different cell types. Mice lacking the transcription factor Ttf1 lack both cell types and thus are unable to develop a thyroid gland. By analysis of Pax8-/- mice, we demonstrate that Pax8 is required for the formation of the follicular cells in the thyroid. We present evidence that Pax8 is necessary for providing cues for the differentiation of competent endoderm primordia into thyroxin-producing follicular cells.

Animals↗
PubMed2003

Cell-specific expression of the glucose-dependent insulinotropic polypeptide gene functions through a GATA and an ISL-1 motif in a mouse neuroendocrine tumor cell line.

BACKGROUND/AIMS: Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino acid gastrointestinal regulatory peptide that, in the presence of glucose, stimulates insulin secretion from beta-cells. GIP is expressed in gastrointestinal K-cells. Prior analysis of the GIP promoter demonstrated that 193 bases of the promoter are required to direct cell specific expression. Here we sought to identify and characterize the transcription factors involved. RESULTS: By mutational analysis of the GIP promoter in a neuroendocrine cell line (STC-1), we identified two regions located between bases -193 and -182 and bases -156 and -151 that, when independently altered, were responsible for a 90% and 85% reduction in transcription, respectively. When we compared these two regions with known motifs from transcription factor databases, we identified the cis elements as potential GATA and ISL-1 binding sites. With subsequent electrophoretic mobility shift analysis (EMSA) using STC-1 nuclear extracts, we demonstrated the ability of these regions to form specific DNA protein complexes. Furthermore, we utilized antisera to confirm the specific binding of GATA-4 to the upstream site and ISL-1 to the downstream element. CONCLUSION: These findings provide evidence for the involvement of the transcription factors GATA-4 and ISL-1 in the cell-specific expression of the GIP gene.

Animals↗