Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Essential gene”

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 577 records · Page 32Linked to original sources
PubMed2006

Caenorhabditis elegans dpy-14: an essential collagen gene with unique expression profile and physiological roles in early development.

We describe the molecular characterisation of Caenorhabditis elegans dpy-14, a gene encoding an essential cuticular collagen annotated as col-59. Expression of dpy-14 starts at the 16 E cell stage, making it the earliest-expressing collagen reported to date. SAGE data and dpy-14 promoter::GFP reporter constructs indicate that the gene is transcribed mainly during embryogenesis, specifically in ciliated neurons and hypoderm. Water permeability assays and lectin staining showed that a mutation in the DPY-14 collagen results in defects in the channels of the amphids, which are a class of ciliated neuron, while the amphids appear morphologically normal by dye filling methods. Behavioural assays showed that the ciliated neurons expressing the gene are functional in dpy-14 mutants. All together, our data suggest that ciliated neurons and their hypodermal support cells collaborate in the transcription and synthesis of DPY-14, which then becomes a component of the amphid channels but not of the amphids proper. Interestingly, seam cells of dpy-14 mutants do not properly fuse to form a syncytium. This novel phenotype due to collagen mutations further stresses that dpy-14 plays a fundamental role in C. elegans physiology, since it is required for the proper development of the hypoderm.

Amino Acid Sequence↗
PubMed1999

The MET3 promoter: a new tool for Candida albicans molecular genetics.

A central technique used to investigate the role of a Candida albicans gene is to study the phenotype of a cell in which both copies of the gene have been deleted. To date, such investigations can only be undertaken if the gene is not essential. We describe the use of the Candida albicans MET3 promoter to express conditionally an essential gene, so that the consequences of depletion of the gene product may be investigated. The effects of environmental conditions on its expression were investigated, using GFP as a reporter gene. The promoter showed an approximately 85-fold range of expression, according to the presence or absence of either methionine or cysteine in concentrations in excess of 1 mM. In the presence of either amino acid, expression was reduced to levels that were close to background. We used URA3 as a model to demonstrate that the MET3 promoter could control the expression of an essential gene, provided that a mixture of both methionine and cysteine was used to repress the promoter. We describe an expression vector that may be used to express any gene under the control of the MET3 promoter and a vector that may be used to disrupt a gene and simultaneously place an intact copy under the control of the MET3 promoter. During the course of these experiments, we discovered that directed integration into the RP10 locus gives a high frequency of transformation, providing a means to solve a long-standing problem in this field.

Antigens, Fungal↗
PubMed2003

[Correlation analysis between WNK4 gene and essential hypertension].

OBJECTIVE: To investigate association of mutation in WNK4 gene with essential hypertension and to analyze the expression of WNK4 gene. METHODS: cSNP in WNK4 gene in a small samples was detected by sequencing, then PCR-RFLP was performed in 98 patients with essential hypertension and 95 control subjects. The expression profile of WNK4 gene was tested by RT-PCR. RESULTS: A cSNP was detected in WNK4 gene exon7 G1662A, and there were significant differences in the distribution of allele frequency of G1662A between essential hypertension group and control group. WNK4 gene were expressed in the tissues of kidney, brain, lung, heart, spleen and intestine of fetus. CONCLUSION: WNK4 gene is well correlated with essential hypertension.

Adult↗
PubMed1991

S. pombe gene sds22+ essential for a midmitotic transition encodes a leucine-rich repeat protein that positively modulates protein phosphatase-1.

The fission yeast dis2+ gene encodes one of the two type 1 protein phosphatases (PP1) in this organism. Its semidominant mutant dis2-11 is defective in mitosis. Here we report the characterization of a high dosage suppressor, sds22+, that complements dis2-11. Sequencing of the cloned sds22+ gene predicts a novel 30 kd protein, which consists almost entirely of leucine-rich 22 amino acid repeats and is enriched in the insoluble nuclear fraction. sds22+ is an essential gene required for the mitotic metaphase/anaphase transition; gene disruption causes cell cycle arrest at midmitosis. Unexpectedly, the sds22+ gene becomes dispensable upon high dosage of the PP1 genes. The sds22+ product appears to facilitate PP1-dependent dephosphorylation, but does not substitute PP1. We propose that the sds22+ protein forms a repeating helical rod that is capable of enhancing a PP1-dependent dephosphorylation activity that is essential in midmitosis.

Amino Acid Sequence↗
PubMed2003

Haplotype analysis of the human renin gene and essential hypertension.

The human renin gene is an attractive candidate for involvement in the underlying cause of essential hypertension (EH). Despite extensive examination, the relation between the renin gene and hypertension remains unclear. The aims of the present study were to discover new genetic markers of EH and to investigate the relations between polymorphisms of the renin gene and EH in the Japanese. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we isolated 3 novel variants of the renin gene; a single nucleotide polymorphism (SNP) in intron 4 (T+17int4G), a variable number of tandem repeats (VNTR) polymorphism in intron 7, and a missense mutation in exon 9 (G1051A). We performed an association study with these polymorphisms in 212 patients with EH and 209 age-matched normotensive (NT) subjects. The frequency of genotypes VNTR and T+17int4G did not differ significantly between the 2 groups, whereas the overall distribution of G1051A was significantly different between EH and NT. Haplotype analysis revealed that the overall distribution of haplotypes differed significantly between the EH and NT groups. PRA levels in patients with EH with the G/G genotype were significantly higher than in subjects with EH with G/A and A/A genotypes. These data suggest that the missense mutation in exon 9 may affect the enzymatic function of renin and consequently may be involved in the etiology of hypertension.

Adult↗
PubMed2004

Integrated physical map of the human essential tremor gene region (ETM2) on chromosome 2p24.3-p24.2.

A gene for autosomal dominant familial essential tremor maps to a 9.1 cM interval flanked by loci D2S224 and D2S405 (ETM2) on human chromosome 2p24.3-p24.2. The recombinatorial boundaries of the interval were refined on a radiation hybrid map to a 123 cR minimal critical region (MCR) between D2S224 and D2S2221. High-throughput non-isotopic screening of bacterial artificial chromosomes (BACs) was used to assemble a physical map of the region. A scaffold BAC map of 31 overlapping clones was ordered by their sequence tagged site (STS) content using PCR and Southern blotting. A complementary 3.9 Mb integrated physical map of the human ETM2 region was constructed by identifying GenBank contigs that contained seven BAC DNA sequences and common STSs. Thirty-three transcripts including five known genes (MATN3, LAPTM4A, SDC1, PUM2, and APOB) were identified in the MCR and ordered on an integrated contig by PCR and virtual mapping. This physical map will provide a template for genomic sequencing and the identification of a gene for essential tremor.

Chromosomes, Artificial, Bacterial↗
PubMed1998

Lethal mutations defining 112 complementation groups in a 4.5 Mb sequenced region of Caenorhabditis elegans chromosome III.

The central gene cluster of chromosome III was one of the first regions to be sequenced by the Caenorhabditis elegans genome project. We have performed an essential gene analysis on the left part of this cluster, in the region around dpy-17III balanced by the duplication sDp3. We isolated 151 essential gene mutations and characterized them with regard to their arrest stages. To facilitate positioning of these mutations, we generated six new deficiencies that, together with preexisting chromosomal rearrangements, subdivide the region into 14 zones. The 151 mutations were mapped into these zones. They define 112 genes, of which 110 were previously unidentified. Thirteen of the zones have been anchored to the physical sequence by polymerase chain reaction deficiency mapping. Of the 112 essential genes mapped, 105 are within these 13 zones. They span 4.2 Mb of nucleotide sequence. From the nucleotide sequence data, 920 genes are predicted. From a Poisson distribution of our mutations, we predict that 234 of the genes will be essential genes. Thus, the 105 genes constitute 45% of the estimated number of essential genes in the physically defined zones and between 2 and 5% of all essential genes in C. elegans.

Animals↗
PubMed2000

kurtz, a novel nonvisual arrestin, is an essential neural gene in Drosophila.

The kurtz gene encodes a novel nonvisual arrestin. krz is located at the most-distal end of the chromosome 3R, the third gene in from the telomere. krz is expressed throughout development. During early embryogenesis, krz is expressed ubiquitously and later is localized to the central nervous system, maxillary cirri, and antennal sensory organs. In late third instar larvae, krz message is detected in the fat bodies, the ventral portion of the thoracic-abdominal ganglia, the deuterocerebrum, the eye-antennal imaginal disc, and the wing imaginal disc. The krz(1) mutation contains a P-element insertion within the only intron of this gene and results in a severe reduction of function. Mutations in krz have a broad lethal phase extending from late embryogenesis to the third larval instar. The fat bodies of krz(1) larva precociously dissociate during the midthird instar. krz(1) is a type 1 melanotic tumor gene; the fat body is the primary site of melanotic tumor formation during the third instar. We have functionally rescued these phenotypes with both genomic and cDNA transgenes. Importantly, the expression of a full-length krz cDNA within the CNS rescues the krz(1) lethality. These experiments establish the krz nonvisual arrestin as an essential neural gene in Drosophila.

Animals↗
PubMed2007

Bacillus minimum genome factory: effective utilization of microbial genome information.

In 1997, the complete genomic DNA sequence of Bacillus subtilis (4.2 Mbp) was determined and 4100 genes were identified [Kunst, Ogasawara, Moszer, Albertini, Alloni, Azevedo, Bertero, Bessieres, Bolotin, Borchert, S. et al. (1997) Nature 90, 249-256]. In addition, B. subtilis, which shows an excellent ability to secrete proteins (enzymes) and antibiotics in large quantities outside the cell, plays an important role in industrial and medical fields. It is necessary to clarify the genes involved in the production of compounds by understanding the network of these 4100 genes and the proceeding analysis of genes of unknown functions. In promoting such a study, it is expected that the regulatory system of B. subtilis can be simplified by the creation of a Bacillus strain with a reduced genome by discriminating genes unnecessary for the production of proteins from essential genes, and deleting as many of these unnecessary genes as possible, which may help to understand this complex network of genes. We have previously distinguished essential and non-essential genes by evaluating the growth and enzyme-producing properties of strains of B. subtilis in which about 3000 genes (except 271 essential genes) have been disrupted or deleted singly, and have successfully utilized the findings from these studies in creating the MG1M strain with an approx. 1 Mbp deletion by serially deleting 17 unnecessary regions from the genome. This strain showed slightly reduced growth in enzyme-production medium, but no marked morphological changes. Moreover, we confirmed that the MG1M strain had cellulase and protease productivity comparable with that of the B. subtilis 168 strain, thus demonstrating that genome reduction does not contribute to a negative influence on enzyme productivity.

Bacillus subtilis↗
PubMed1998

Crosses between diabetic BB/OK and wild rats confirm that a third gene is essential for diabetes development.

Several crossing studies with diabetic BB rats have shown that in addition to the lymphopenia (Iddm1) and the MHC class II genes of the RT1U haplotype (Iddm2) there are further non-MHC genes essential for diabetes development. Because diabetes-resistant inbred rat strains may be homozygous for one of the diabetogenic non-MHC genes, masking the expression of diabetogenic genes and leading to an underestimation of the number of diabetogenic genes, we crossed wild and diabetic BB/OK rats. The F1 hybrids were backcrossed onto diabetic female (BC1W-F, n=97) and male BB/OK rats (BC1W-M, n=98) transferred to a specified-pathogen-free environment and studied for the frequency and age at onset of diabetes up to an age of 30 weeks. Comparing the results of these BC1 W hybrids with similarly derived hybrids using diabetes-resistant DA rats (BC1DA-F, n=113; BC1DA-M, n=216), the diabetes frequency in total was comparable indicating the action of three recessive genes. The percentage of diabetics in Iddm1 and Iddm2 homozygotes confirmed the existence of the third gene, Iddm3, but there were some sex differences; significantly more male than female BC1W-F and significantly more BC1DA-M than BC1DA-F males were diabetic. Regarding the age at onset, the BC1W-F hybrids manifested not only significantly earlier, but also more uniformly than BC1DA-F and BC1-M hybrids.

Age of Onset↗
PubMed2006

Why does Kluyveromyces lactis not grow under anaerobic conditions? Comparison of essential anaerobic genes of Saccharomyces cerevisiae with the Kluyveromyces lactis genome.

Although some yeast species, e.g. Saccharomyces cerevisiae, can grow under anaerobic conditions, Kluyveromyces lactis cannot. In a systematic study, we have determined which S. cerevisiae genes are required for growth without oxygen. This has been done by using the yeast deletion library. Both aerobically essential and nonessential genes have been tested for their necessity for anaerobic growth. Upon comparison of the K. lactis genome with the genes found to be anaerobically important in S. cerevisiae, which yielded 20 genes that are missing in K. lactis, we hypothesize that lack of import of sterols might be one of the more important reasons that K. lactis cannot grow in the absence of oxygen.

Anaerobiosis↗
PubMed1987

The SPT6 gene is essential for growth and is required for delta-mediated transcription in Saccharomyces cerevisiae.

Mutations in the Saccharomyces cerevisiae SPT6 gene were originally identified as one class of extragenic suppressors of Ty and delta insertion mutations in the 5' noncoding regions of HIS4 and LYS2. We cloned SPT6 and constructed a null allele by gene disruption. Haploid spores carrying the spt6 null allele were inviable, indicating that the SPT6 gene is essential for mitotic growth. SPT6 was mapped to the right arm of chromosome VII, 44 centimorgans (cM) from ADE6 and 9 cM from CLY8. We showed that spt6 mutations suppress delta insertion mutations at the level of transcription but have no qualitative or quantitative effect on Ty transcription. In addition, we observed interesting SPT6 gene dosage effects. An SPT6 strain containing a high-copy-number plasmid clone of SPT6 showed suppression of delta insertion mutations, and a diploid strain with half its normal dose of SPT6 (SPT6/spt6 null) also exhibited suppression of delta insertion mutations. Therefore, having either too many or too few copies of SPT6 causes a mutant phenotype. Finally, this study and that in the accompanying paper (L. Neigeborn, J. L. Celenza, and M. Carlson, Mol. Cell. Biol. 7:679-686, 1986) showed that spt6 and ssn20 mutations (isolated as suppressors of snf2 and snf5 [sucrose nonfermenting] mutations) identify the same gene. SPT6 and SSN20 have the same genetic map position and share an identical restriction map. Furthermore, spt6 and ssn20 mutations fail to complement each other, and ssn20 mutations suppress solo delta insertion mutations at HIS4 and LYS2. These results, taken in conjunction with the SPT6 dosage effects and the fact that SPT6 is an essential gene, suggest that SPT6 plays a fundamental role in cellular transcription, perhaps by interaction with other transcription factors.

Alleles↗
PubMed1998

A genome-based approach for the identification of essential bacterial genes.

We have used comparative genomics to identify 26 Escherichia coli open reading frames that are both of unknown function (hypothetical open reading frames or y-genes) and conserved in the compact genome of Mycoplasma genitalium. Not surprisingly, these genes are broadly conserved in the bacterial world. We used a markerless knockout strategy to screen for essential E. coli genes. To verify this phenotype, we constructed conditional mutants in genes for which no null mutants could be obtained. In total we identified six genes that are essential for E. coli (yhbZ, ygjD, ycfB, yfil, yihA, and yjeQ). The respective orthologs of the genes yhbZ, ygjD, ycfB, yjeQ, and yihA are also essential in Bacillus subtilis. This low number of essential genes was unexpected and might be due to a characteristic of the versatile genomes of E. coli and B. subtilis that is comparable to the phenomenon of nonorthologous gene displacement. The gene ygjD, encoding a sialoglycoprotease, was eliminated from a minimal genome computationally derived from a comparison of the Haemophilus influenzae and M. genitalium genomes. We show that ygjD and its ortholog ydiE are essential in E. coli and B. subtilis, respectively. Thus, we include this gene in a minimal genome. This study systematically integrates comparative genomics and targeted gene disruptions to identify broadly conserved bacterial genes of unknown function required for survival on complex media.

Amino Acid Sequence↗
PubMed1999

Selective killing of cancer cells based on loss of heterozygosity and normal variation in the human genome: a new paradigm for anticancer drug therapy.

Most drugs for cancer therapy are targeted to relative differences in the biological characteristics of cancer cells and normal cells. The therapeutic index of such drugs is theoretically limited by the magnitude of such differences, and most anticancer drugs have considerable toxicity to normal cells. Here we describe a new approach for developing anticancer drugs. This approach, termed variagenic targeting, exploits the absolute difference in the genotype of normal cells and cancer cells arising from normal gene sequence variation in essential genes and loss of heterozygosity (LOH) occurring during oncogenesis. The technology involves identifying genes that are: 1) essential for cell survival; 2) are expressed as multiple alleles in the normal population because of the presence of one or more nucleotide polymorphisms; and 3) are frequently subject to LOH in several common cancers. An allele-specific drug inhibiting the essential gene remaining in cancer cells would be lethal to the malignant cell and would have minimal toxicity to the normal heterozygous cell that retains the drug-insensitive allele. With antisense oligonucleotides designed to target two alternative alleles of replication protein A, 70-kDa subunit (RPA70) we demonstrate in vitro selective killing of cancer cells that contain only the sensitive allele of the target gene without killing cells expressing the alternative RPA70 allele. Additionally, we identify several other candidate genes for variagenic targeting. This technology represents a new approach for the discovery of agents with high therapeutics indices for treating cancer and other proliferative disorders.

Antineoplastic Agents↗
PubMed1999

The Hansenula polymorpha PDD1 gene product, essential for the selective degradation of peroxisomes, is a homologue of Saccharomyces cerevisiae Vps34p.

Via functional complementation we have isolated the Hansenula polymorpha PDD1 gene essential for selective, macroautophagic peroxisome degradation. HpPDD1 encodes a 116 kDa protein with high similarity (42% identity) to Saccharomyces cerevisiae Vps34p, which has been implicated in vacuolar protein sorting and endocytosis. Western blotting experiments revealed that HpPDD1 is expressed constitutively. In a H. polymorpha pdd1 disruption strain peroxisome degradation is fully impaired. Sequestered peroxisomes, typical for the first stage of peroxisome degradation in H. polymorpha, were never observed, suggesting that HpPdd1p plays a role in the tagging of redundant peroxisomes and/or sequestration of these organelles from the cytosol. Possibly, HpPdd1p is the functional homologue of ScVps34p, because-like S. cerevisiae vps34 mutants-H. polymorpha pdd1 mutants are temperature-sensitive for growth and are impaired in the sorting of vacuolar carboxypeptidase Y. Moreover, HpPdd1p is associated to membranes, as was also observed for ScVps34p.

Alcohol Oxidoreductases↗
PubMed2003

Essential Bacillus subtilis genes.

To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximately 4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from bacteria with small genomes. Unexpectedly, most genes involved in the Embden-Meyerhof-Parnas pathway are essential. Identification of unknown and unexpected essential genes opens research avenues to better understanding of processes that sustain bacterial life.

Bacillus subtilis↗
PubMed1999

Allelic variants in the interleukin-6 gene and essential hypertension in Japanese women.

Genes that can be implicated in hypertension in experimental animals are plausible candidates in the pathogenesis of human hypertension. A recent genome-wide search for quantitative-trait loci (QTL) in hypertensive rats revealed a strong correlation between the interleukin-6 (IL-6) locus on rat chromosome 4 and systolic, diastolic, and mean arterial pressure in this mammalian species. To investigate a possible association between genetic variations of the IL-6 gene and hypertension in humans, we identified two novel single-nucleotide sequence variations, a C/G substitution at -634 in the promoter region and a G/A substitution at 4391 in a 3' non-coding portion of exon 5, and a previous reported sequence variant, an A/T variation in the composition of the AnTn tract around -447 in the promoter region (Fishman D et al. J Clin Invest 1998; 102: 1369-1376), within a test population of 96 Japanese subjects. Allelic associations involving these variations were analyzed in 150 hypertensive and 143 normotensive Japanese women. The distribution of alleles of the three polymorphisms, as well as a dinucleotide repeat present at the IL-6 locus, was similar in the two groups. Therefore, the IL-6 gene appears to play a minimal role in the genetic etiology of essential hypertension in Japanese women.

Aged↗
PubMed1992

Genetic analysis and complementation by germ-line transformation of lethal mutations in the unc-22 IV region of Caenorhabditis elegans.

The subject of this study is the organization of essential genes in the 2 map-unit unc-22 IV region of the Caenorhabditis elegans genome. With the goal of achieving mutational saturation of essential genes in this region, 6491 chromosomes mutagenized with ethyl methanesulfonate (EMS) were screened for the presence of lethal mutations in the unc-22 region. The genetic analysis of 21 lethal mutations in the unc-22 region resulted in the identification of 6 new essential genes, making a total of 36 characterized to date. A minimum of 49 essential genes are estimated to lie in this region. A set of seven formaldehyde-induced deficiencies of unc-22 and surrounding loci were isolated to facilitate the positioning of essential genes on the genetic and physical maps. In order to study essential genes at the molecular level, our approach was to rescue lethal mutations by the injection of genomic DNA in the form of cosmid clones into the germ-line of balanced heterozygotes carrying a lethal mutation. The cosmid clones containing let-56 and let-653 were identified by this method.

Animals↗