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At least 703 records · Page 39Linked to original sources
PubMed1999

Construction of a physical and transcript map for a 1-Mb genomic region containing the urofacial (Ochoa) syndrome gene on 10q23-q24 and localization of the disease gene within two overlapping BAC clones (<360 kb).

Urofacial (Ochoa) syndrome is an autosomal recessive disease characterized by distorted facial expression and urinary abnormalities. Previously, we mapped the UFS gene to chromosome 10q23-q24 and narrowed the interval to one YAC clone of 1410 kb. Here, we have constructed a BAC/PAC contig of the 1-Mb region using STS content mapping with 42 BAC/PAC-end sequences, 9 previously reported and 16 newly identified microsatellite markers, and 14 EST markers. A total of 26 polymorphic microsatellite markers were genotyped for 31 UFS patients from Colombia and 2 patients from the United States. Haplotype analyses suggest that the UFS gene is located within two overlapping BAC clones, a region of <360 kb of DNA sequence. We tested 42 EST markers previously mapped to the D10S1709-D10S603 interval against the BAC/PAC contig and identified 11 ESTs located in the 1-Mb region. Four of the 11 ESTs mapped to the 360-kb UFS critical region. Shotgun sequencing of the two BAC clones and BLASTN search of the EST databases revealed 3 other ESTs contained in the UFS critical region. These results will facilitate the cloning and identification of the UFS gene.

Bacteriophage P1↗
PubMed2002

Overlapping but distinct gene regulation profiles by glucocorticoids and progestins in human breast cancer cells.

Glucocorticoids and progestins bind to receptors that share many structural and functional similarities, including virtually identical DNA recognition specificity. Nonetheless, the two hormones mediate very distinct biological functions. For example, progestins are associated with the incidence and progression of breast cancer, whereas glucocorticoids are growth suppressive in mammary cancer cells. To understand the mechanisms that engender biological specificity, it is necessary to identify genes that are differentially regulated by the two receptors. Here we employ Affymetrix oligonucleotide arrays to compare glucocorticoid- and progestin-regulated gene expression in a human breast cancer cell line. This global analysis reveals that the two hormones regulate overlapping but distinct sets of genes, including 31 genes that are differentially regulated. Surprisingly, the set of differentially regulated genes was almost as large as the set of genes regulated by both hormones. Examination of the set of differentially regulated genes suggests mechanisms behind the distinct growth effects of the two hormones in breast cancer. The differential regulation of four genes representing different regulatory patterns was confirmed by RT-PCR and Northern blot analyses. Treatment with cycloheximide or RU486 indicates that the regulation is a primary, receptor-mediated event. Detailed analyses of genes identified in these studies will furnish a mechanistic understanding of differential regulation by glucocorticoids and progestins.

Breast Neoplasms↗
PubMed1983

Structure and expression of the dnaQ mutator and the RNase H genes of Escherichia coli: overlap of the promoter regions.

A 1.6-kilobase-pair DNA fragment derived from the Escherichia coli chromosome was analyzed by Tn3 transposon insertion and deletion mapping to locate a mutator gene, dnaQ (mutD), and the rnh gene that codes for RNase H. When a strong promoter, PL of lambda phage, was placed at the right- and left-side of the cloned DNA fragment, the dnaQ protein and RNase H, respectively were overproduced. These results suggested that the two genes are transcribed in opposite directions and that their promoters are located in a narrow region between the genes. Nucleotide sequence analysis confirmed this and further revealed that transcriptional and translational initiation signals for the two genes overlap. From the sequence data it was deduced that the dnaQ protein and RNase H consist of 243 and 155 triplets and have molecular weights of 27,500 and 17,500, respectively. dnaQ81 amber mutant showed two codon alterations, CAG(glutamine-195) leads to TAG(amber) and ACA(threonine-193) leads to ATA(isoleucine). The dnaQ-lacZ and the rnh-lacZ fused genes were constructed and hybrid proteins with beta-galactosidase activity were produced. From beta-galactosidase levels it was estimated that the promoter for dnaQ is 5 times more active than that for rnh.

Amino Acid Sequence↗
PubMed1997

Vsx-1 and Vsx-2: two Chx10-like homeobox genes expressed in overlapping domains in the adult goldfish retina.

The genetic linkages of the murine ocular retardation mutation with the Chx10 gene and the murine small eye mutation with the Pax-6 gene has demonstrated the importance of Paired class homeobox genes in the development of the mammalian retina. Previously, we identified a Paired-class homeobox gene, Vsx-1, whose expression in the adult goldfish retina is restricted to the inner nuclear layer (INL) and to postmitotic, differentiating progenitor cells in the growth zone at the retinal peripheral margin, where neurogenesis continues throughout life. Here, we report the molecular cloning and expression pattern of a new Paired class homeobox gene, Vsx-2, in the adult goldfish retina. Like Vsx-1, Vsx-2 expression is highly restricted to the retina in the adult goldfish and overlaps with Vsx-1 expression in the mature INL. At the peripheral margin, Vsx-2 is expressed in mitotically active neuronal progenitors and is downregulated as these cells become postmitotic and begin to differentiate. Comparison of the amino acid sequences of Vsx-2, Vsx-1, Chx10, and C. elegans ceh-10 reveal a conserved homeodomain and a unique domain termed the CVC domain. The similarities of the Vsx-2, Vsx-1, and Chx10 expression patterns suggest that genes containing the CVC domain have conserved functions during retinal development in vertebrates.

Amino Acid Sequence↗
PubMed2002

Organization of six functional mouse alcohol dehydrogenase genes on two overlapping bacterial artificial chromosomes.

Mammalian alcohol dehydrogenases (ADH) form a complex enzyme system based on amino-acid sequence, functional properties, and gene expression pattern. At least four mouse Adh genes are known to encode different enzyme classes that share less than 60% amino-acid sequence identity. Two ADH-containing and overlapping C57BL/6 bacterial artificial chromosome clones, RP23-393J8 and -463H24, were identified in a library screen, physically mapped, and sequenced. The gene order in the complex and two new mouse genes, Adh5a and Adh5b, and a pseudogene, Adh5ps, were obtained from the physical map and sequence. The mouse genes are all in the same transcriptional orientation in the order Adh4-Adh1-Adh5a-Adh5b-Adh5ps-Adh2-Adh3. A phylogenetic tree analysis shows that adjacent genes are most closely related suggesting a series of duplication events resulted in the gene complex. Although mouse and human ADH gene clusters contain at least one gene for ADH classes I-V, the human cluster contains 3 class I genes while the mouse cluster has two class V genes plus a class V pseudogene.

Alcohol Dehydrogenase↗
PubMed1993

Expression of the Rz gene and the overlapping Rz1 reading frame present at the right end of the bacteriophage lambda genome.

The Rz lysis gene of bacteriophage lambda was cloned into the expression vectors, pT7-3 and pT7-7. The recombinant plasmids expressed either a protein of an unexpected 6.5-kDa size (pT7-3H and pSB54) or two proteins of 6.5 and 17.2 kDa (pBH21). The 6.5-kDa protein alone did not complement the lysis defect of the lambda Rz mutant; hence, this protein was not the Rz gene product. Complementation observed as a result of pBH21 expression thus can be ascribed to the 17.2-kDa protein, which agrees with the size based on the nucleotide sequence of Rz. The 6.5 kDa is a product of an open reading frame entirely encompassed within the Rz sequence and denoted by us Rz1. Both proteins were detectable only by autoradiography, which may mean that the genes are expressed at low rates. Polyclonal anti-Rz antibodies (Ab) were obtained by rabbit immunization with a synthetic polypeptide corresponding to an antigenic determinant of Rz defined by a computer program. The Ab reacted with the 17.2-kDa protein resulting from pBH21 expression, as well as with the 17.2-kDa protein present in the induced Escherichia coli W3350(lambda cI857Sam7) lysate.

Amino Acid Sequence↗
PubMed2002

Large-scale prediction of Saccharomyces cerevisiae gene function using overlapping transcriptional clusters.

Genome sequencing has led to the discovery of tens of thousands of potential new genes. Six years after the sequencing of the well-studied yeast Saccharomyces cerevisiae and the discovery that its genome encodes approximately 6,000 predicted proteins, more than 2,000 have not yet been characterized experimentally, and determining their functions seems far from a trivial task. One crucial constraint is the generation of useful hypotheses about protein function. Using a new approach to interpret microarray data, we assign likely cellular functions with confidence values to these new yeast proteins. We perform extensive genome-wide validations of our predictions and offer visualization methods for exploration of the large numbers of functional predictions. We identify potential new members of many existing functional categories including 285 candidate proteins involved in transcription, processing and transport of non-coding RNA molecules. We present experimental validation confirming the involvement of several of these proteins in ribosomal RNA processing. Our methodology can be applied to a variety of genomics data types and organisms.

Algorithms↗
PubMed1999

Troubleshooting in gene splicing by overlap extension: a step-wise method.

A step-wise method for cloning intron-containing genes from genomic DNA is described. The two exons of the human proinsulin gene were separately amplified in two steps using, in the first step, completely homologous primers. This reduces unwanted interactions between mismatched primers and a complex DNA template such as genomic DNA. The fragments were amplified in a second step polymerase chain reaction (PCR) using mismatched primers that incorporated additional bases complementary to the other exon, and these products were spliced together in a third step PCR.

Cloning, Molecular↗
PubMed1998

Sequence analysis of a 62-kb region overlapping the human KLRC cluster of genes.

The NKG2 family of genes (HGMW-approved symbol KLRC) contains at least four members (NKG2-A, -C, -E, and -F) which are localized to human chromosome 12p12.3-p13.2. This region, called the natural killer (NK) complex, encodes for lectin-like genes preferentially expressed on NK cells. One of them, the human CD94 gene (HGMW-approved symbol KLRD1), encodes for a protein that has been shown to be covalently associated with the NKG2-A molecule. In this report, we showed that the NKG2 and CD94 genes are localized in a small region (< 350 kb) and we mapped them in the following order: (NKG2-C/NKG2-A)/NKG2-E/NKG2-F/NKG2-D/CD 94. Sequence analysis of 62 kb spanning the NKG2-A, -E, -F, and -D loci allowed the identification of two LINE elements that could have been involved in the duplication of the NKG2 genes. Presence of one MIR and one L1ME2 element at homologous positions in the NKG2-A and NKG2-F genes is consistent with the existence of rodent NKG2 gene(s). Finally, we mapped the 5'-ends of the NKG2-A transcripts into two separate regions showing the existence of two separate transcriptional control regions upstream of the NKG2-A locus and defining putative promoter elements for these genes.

Antigens, CD↗
PubMedDate not supplied

Carving chaos: genetics and the classification of mood and psychotic syndromes.

Though Kraepelin's century-old division of major mental illness into mood disorder and schizophrenia remains in place, debate abounds over the most appropriate classification. Although these arguments previously rested solely on clinical grounds, they now are rooted in genetics and neurobiology. This article reviews evidence from the fields of genetic epidemiology, linkage, association, cytogenetics, and gene expression. Taken together, these data suggest some overlap in the genes that predispose to bipolar disorder and schizophrenia. One gene, DAOA (D-amino acid oxidase activator, also known as G72), has been repeatedly implicated as an overlap gene, while DISC1 and others may constitute additional shared susceptibility genes. Further, some evidence implicates syndromes of co-occurring mood and psychotic symptoms in association with the putative risk alleles in overlap genes. From a nosologic perspective, the existence of overlap genes, coupled with the genotype-phenotype correlations discovered to date, supports the reality of the much debated schizoaffective disorder. Potential non-overlap syndromes--such as nonpsychotic bipolar disorder or cyclothymic temperament, on the one hand, and negative symptoms or the deficit syndrome, on the other--could turn out to have their own unique genetic determinants. If genotypes are to be the anchor points of a clinically useful system of classification, they must ultimately be shown to inform prognosis, treatment, and prevention. No gene variants have yet met these tests in bipolar disorder or schizophrenia.

Bipolar Disorder↗
PubMed1994

Rps3 and rpl16 genes do not overlap in Oenothera mitochondria: GTG as a potential translation initiation codon in plant mitochondria?

Characterization of the Oenothera mitochondrial ribosomal gene cluster rps19-rps3-rpl16 shows the two genes rps3 and rpl16 to be separated by 9 nucleotides. The first codon of rpl16 is a GTG codon for valine and the only potential translational start. This GTG codon is conserved at the same position in maize, Petunia and Marchantia mitochondria, while sequences diverge upstream. These observations suggest that GTG at least at this position may act as translation initiation codon in plant mitochondria. Analysis of RNA editing suggests both genes to code for functional ribosomal proteins in Oenothera mitochondria. A duplication/recombination event at a decanucleotide in the intron of rps3 created a pseudogene missing part of the intron and the 3' exon.

Amino Acid Sequence↗
PubMed2004

Genetics of monoamine metabolites in baboons: overlapping sets of genes influence levels of 5-hydroxyindolacetic acid, 3-hydroxy-4-methoxyphenylglycol, and homovanillic acid.

BACKGROUND: Monoamine neurotransmitters (serotonin, dopamine, and norepinephrine) are associated with several psychiatric disorders. Limited evidence suggests that monoamine levels are heritable, but no information concerning genetic relationships among monoamines is available. Further genetic analysis can help explain phenotypic correlations among monoamine levels and might eventually help identify genes involved in response to therapy or risk of psychopathology. METHODS: Levels of the monoamine metabolites homovanillic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA), and 3-hydroxy-4-methoxyphenylglycol (MHPG) were measured in cerebrospinal fluid from 271 baboons (Papio hamadryas). Variance components methods were used to estimate heritabilities, and multivariate analyses were used to estimate genetic correlations (pleiotropy) and environmental correlations between metabolites. RESULTS: Each metabolite exhibited significant heritability in baboons (5-HIAA: h(2) =.30 +/-.17; MHPG: h(2) =.36 +/-.16; HVA: h(2) =.50 +/-.19). Multivariate analyses revealed genetic correlations between 5-HIAA and HVA and between HVA and MHPG. Environmental correlations were found between 5-HIAA and HVA and between 5-HIAA and MHPG. CONCLUSIONS: Overlapping, nonidentical sets of genes influence individual variation in 5-HIAA, MHPG, and HVA levels among baboons. The phenotypic correlation between 5-HIAA and HVA observed in nonhuman primates and humans is likely due to both shared genetic and environmental factors. Genetic analyses of monoamine levels in primates can provide novel information concerning the genetics of variation among humans.

Analysis of Variance↗
PubMed1979

The smallest genome RNA segment of influenza virus contains two genes that may overlap.

The genome of influenza virus consists of eight segments of single-stranded RNA, each of which encodes a different polypeptide. In addition to the eight recognized gene products, the virus specifies a distinct smaller nonstructural polypeptide (NS2), which is translated from a separate species of virus-specific mRNA. The location on the virus genome of the gene encoding this polypeptide was investigated by hybridization of the NS2 mRNA with isolated subgenomic RNA species, and by correlation of the inheritance of a strain-specific NS2 with inheritance of particular genome RNA segments during recombination between two different virus strains. The genetic information for NS2 was found to reside in the smallest genome RNA segment of the virion, which also encodes the NS1 polypeptide. Considering the sizes of the molecules involved, it is likely that the coding sequences for the two polypeptides overlap.

Genes, Viral↗
PubMed2006

Functionality of unspliced XBP1 is required to explain evolution of overlapping reading frames.

Eukaryotic genes with overlapping reading frames exemplify some of the most striking biological phenomena. Transcript of one such gene, the gene encoding X-box protein (XBP1), has evolved a mechanism for "on-demand" switching of translation between two overlapping reading frames. Despite the existence of this elaborate system, only one reading frame was believed to be functional. Here, we show that XBP1 evolves in a fashion that is only consistent with functionality of both reading frames. Our study provides a novel evolutionary framework for the analysis of loci with overlapping reading frames, which can be used for identification and analyses of novel dual-coding genes.

Animals↗
PubMed1995

Mutations in paralogous Hox genes result in overlapping homeotic transformations of the axial skeleton: evidence for unique and redundant function.

Hoxd-4 (previously known as Hox-4.2 and -5.1) is a mouse homeobox-containing gene homologous to the Drosophila homeotic gene Deformed. During embryogenesis, Hoxd-4 is expressed in the presumptive hindbrain and spinal cord, prevertebrae, and other tissues. In the adult, Hoxd-4 transcripts are expressed predominantly in the testis and kidney, and to a lesser extent in intestine and heart. To understand the role of Hoxd-4 during mouse embryogenesis, we generated Hoxd-4 mutant mice. Mice heterozygous or homozygous for the Hoxd-4 mutation exhibit homeotic transformations of the second cervical vertebrae (C2) to the first cervical vertebrae (C1) and malformations of the neural arches of C1 to C3 and of the basioccipital bone. The phenotype was incompletely penetrant and showed variable expressivity on both an F2 hybrid and 129 inbred genetic background. The mutant phenotype was detected in the cartilaginous skeleton of 14.5-day (E14.5) mutant embryos but no apparent differences were detected in the somites of E9.5 mutant embryos, suggesting that the abnormalities develop after E9.5 perhaps during or after resegmentation of the somites to form the prevertebrae. These results suggest that Hoxd-4 plays a role in conferring position information along the anteroposterior axis in the skeleton. The phenotypic similarities and differences between Hoxd-4 and previously reported Hoxa-4 and Hoxb-4 mutant mice suggest that Hox gene paralogs have both redundant and unique functions.

Animals↗
PubMed1997

Identification of the vertebrate Iroquois homeobox gene family with overlapping expression during early development of the nervous system.

In Drosophila the decision processes between the neural and epidermal fate for equipotent ectodermal cells depend on the activity of proneural genes. Members of the Drosophila Iroquois-Complex (Iro-C) positively regulate the activity of certain proneural AS-C genes during the formation of external sensory organs. We have identified and characterized three mouse Iroquois-related genes: Irx1, -2 and -3, which have a homeodomain very similar to that of the Drosophila Iro-C genes. The sequence similarity implies that these three genes represent a separate homeobox family. All three genes are expressed with distinct spatio/temporal patterns during early mouse embryogenesis. These patterns implicate them in a number of embryonic developmental processes: the A/P and D/V patterning of specific regions of the central nervous system (CNS), and regionalization of the otic vesicle, branchial epithelium and limbs.

Amino Acid Sequence↗
PubMed2005

Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis.

Tamoxifen, a selective oestrogen receptor modulator, has been used in the treatment of all stages of hormone-responsive breast cancer. However, tamoxifen shows partial oestrogenic activity in the uterus and its use has been associated with an increased incidence of endometrial cancer. The molecular explanation for these observations is not known. Here we show that tamoxifen and oestrogen have distinct but overlapping target gene profiles. Among the overlapping target genes, we identify a paired-box gene, PAX2, that is crucially involved in cell proliferation and carcinogenesis in the endometrium. Our experiments show that PAX2 is activated by oestrogen and tamoxifen in endometrial carcinomas but not in normal endometrium, and that this activation is associated with cancer-linked hypomethylation of the PAX2 promoter.

Animals↗
PubMed2006

The Populus homeobox gene ARBORKNOX1 reveals overlapping mechanisms regulating the shoot apical meristem and the vascular cambium.

Secondary growth is supported by a dividing population of meristematic cells within the vascular cambium whose daughter cells are recruited to differentiate within secondary phloem and xylem tissues. We cloned a Populus Class 1 KNOX homeobox gene, ARBORKNOX1 (ARK1), which is orthologous to Arabidopsis SHOOT MERISTEMLESS (STM). ARK1 is expressed in the shoot apical meristem (SAM) and the vascular cambium, and is down-regulated in the terminally differentiated cells of leaves and secondary vascular tissues that are derived from these meristems. Transformation of Populus with either ARK1 or STM over-expression constructs results in similar morphological phenotypes characterized by inhibition of the differentiation of leaves, internode elongation, and secondary vascular cell types in stems. Microarray analysis showed that 41% of genes up-regulated in the stems of ARK1 over-expressing plants encode proteins involved in extracellular matrix synthesis or modification, including proteins involved in cell identity and signaling, cell adhesion, or cell differentiation. These gene expression differences are reflected in alterations of cell wall biochemistry and lignin composition in ARK1 over-expressing plants. Our results suggest that ARK1 has a complex mode of action that may include regulating cell fates through modification of the extracellular matrix. Our findings support the hypothesis that the SAM and vascular cambium are regulated by overlapping genetic programs.

Amino Acid Sequence↗