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Novel Genes (novel + gene)
Kinds of Novel Genes Selected AbstractsIsolation of Two Novel Genes, Down-regulated in Gastric CancerCANCER SCIENCE, Issue 5 2000Yoshie Yoshikawa Using a differential display technique, we identified two genes that are down-regulated in human gastric cancer tissue as compared to normal gastric mucosa. The down-regulated expression of these genes in gastric cancer tissue was confirmed by northern blotting analysis and RT-PCR. One, CA11, was a novel gene expressed predominantly in the stomach and was depleted in all of the gastric cancer cell lines examined. The other gene, GC36, was homologous to the digestive tract-specific calpain gene, nCL-4. The expression of both GC36 and nCL-4 was suppressed or depleted in gastric cancer cell lines of differentiated and poorly differentiated types. This is the first report of genes, the expression of which is down-regulated with considerable frequency in gastric cancer. [source] Novel genes involved in canonical Wnt/, -catenin signaling pathway in early Ciona intestinalis embryosDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 4 2008Shuichi Wada We report here characterization of five genes for novel components of the canonical Wnt/, -catenin signaling pathway. These genes were identified in the ascidian Ciona intestinalis through a loss-of-function screening for genes required for embryogenesis with morpholinos, and four of them have counterparts in vertebrates. The five genes we studied are as follows: Ci-PGAP1, a Ciona orthologue of human PGAP1, which encodes GPI (glycosylphosphatidylinositol) inositol-deacylase, Ci-ZF278, a gene encoding a C2H2 zinc-finger protein, Ci-C10orf11, a Ciona orthologue of human C10orf11 that encodes a protein with leucine-rich repeats, Ci-Spatial/C4orf17, a single counterpart for two human genes Spatial and C4orf17, and Ci-FLJ10634, a Ciona orthologue of human FLJ10634 that encodes a member of the J-protein family. Knockdown of each of the genes mimicked , -catenin knockdown and resulted in suppression of the expression of , -catenin downstream genes (Ci-FoxD, Ci-Lhx3, Ci-Otx and Ci-Fgf9/16/20) and subsequent endoderm formation. For every gene, defects in knockdown embryos were rescued by overexpression of a constitutively active form, but not wild-type, of Ci- , -catenin. Dosage-sensitive interactions were found between Ci-,-catenin and each of the genes. These results suggest that these five genes act upstream of or parallel to Ci- , -catenin in the Wnt/, -catenin signaling pathway in early Ciona embryos. [source] Novel genes involved in Ciona intestinalis embryogenesis: Characterization of gene knockdown embryosDEVELOPMENTAL DYNAMICS, Issue 7 2007Mayuko Hamada Abstract The sequenced genome of the urochordate ascidian Ciona intestinalis contains nearly 2,500 genes that have vertebrate homologues, but their functions are as yet unknown. To identify novel genes involved in early chordates embryogenesis, we previously screened 200 Ciona genes by knockdown experiments using specific morpholino oligonucleotides and found that suppression of the translation of 40 genes caused embryonic defects (Yamada et al. [2003] Development 130:6485,6495). We have since examined an additional 304 genes, that is, screening 504 genes overall, and a total of 111 genes showed morphological defects when gene function was suppressed. We further examined the role of these genes in the differentiation of six major tissues of the embryo: endoderm, muscle, epidermis, neural tissue, mesenchyme, and notochord. Based on the similarity of phenotypes of gene knockdown embryos, genes were categorized into several groups, with the suggestion that the genes within a given group are involved in similar developmental processes. For example, five were shown to be novel genes that are likely involved in ,-catenin,mediated endoderm formation. The type of large-scale screening used is, therefore, a powerful approach to identify novel genes with significant developmental functions, the details of which will be determined in future studies. Developmental Dynamics 236:1820,1831, 2007. © 2007 Wiley-Liss, Inc. [source] Novel genes in cell cycle control and lipid metabolism with dynamically regulated binding sites for sterol regulatory element-binding protein 1 and RNA polymerase II in HepG2 cells detected by chromatin immunoprecipitation with microarray detectionFEBS JOURNAL, Issue 7 2009Mehdi Motallebipour Sterol regulatory element-binding proteins 1 and 2 (SREBP-1 and SREBP-2) are important regulators of genes involved in cholesterol and fatty acid metabolism, but have also been implicated in the regulation of the cell cycle and have been associated with the pathogenesis of type 2 diabetes, atherosclerosis and obesity, among others. In this study, we aimed to characterize the binding sites of SREBP-1 and RNA polymerase II through chromatin immunoprecipitation and microarray analysis in 1% of the human genome, as defined by the Encyclopaedia of DNA Elements consortium, in a hepatocellular carcinoma cell line (HepG2). Our data identified novel binding sites for SREBP-1 in genes directly or indirectly involved in cholesterol metabolism, e.g. apolipoprotein C-III (APOC3). The most interesting biological findings were the binding sites for SREBP-1 in genes for host cell factor C1 (HCFC1), involved in cell cycle regulation, and for filamin A (FLNA). For RNA polymerase II, we found binding sites at classical promoters, but also in intergenic and intragenic regions. Furthermore, we found evidence of sterol-regulated binding of SREBP-1 and RNA polymerase II to HCFC1 and FLNA. From the results of this work, we infer that SREBP-1 may be involved in processes other than lipid metabolism. [source] In Vivo Gene Transfer Studies on the Regulation and Function of the Vasopressin and Oxytocin GenesJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2003D. Murphy Abstract Novel genes can be introduced into the germline of rats and mice by microinjecting fertilized one-cell eggs with fragments of cloned DNA. A gene sequence can thus be studied within the physiological integrity of the resulting transgenic animals, without any prior knowledge of its regulation and function. These technologies have been used to elucidate the mechanisms by which the expression of the two genes in the locus that codes for the neuropeptides vasopressin and oxytocin is confined to, and regulated physiologically within, specific groups of neurones in the hypothalamus. A number of groups have described transgenes, derived from racine, murine and bovine sources, in both rat and mouse hosts, that mimic the appropriate expression of the endogenous vasopressin and genes in magnocellular neurones (MCNs) of the supraoptic and paraventricular nuclei. However, despite considerable effort, a full description of the cis -acting sequences mediating the regulation of the vasopressin-oxytocin locus remains elusive. Two general conclusions have nonetheless been reached. First, that the proximal promoters of both genes are unable to confer any cell-specific regulatory controls. Second, that sequences downstream of the promoter, within the structural gene and/or the intergenic region that separates the two genes, are crucial for appropriate expression. Despite these limitations, sufficient knowledge has been garnered to specifically direct the expression of reporter genes to vasopressin and oxytocin MCNs. Further, it has been shown that reporter proteins can be directed to the regulated secretory pathway, from where they are subject to appropriate physiological release. The use of MCN expression vectors will thus enable the study of the physiology of these neurones through the targeted expression of biologically active molecules. However, the germline transgenic approach has a number of limitations involving the interpretation of phenotypes, as well as the large cost, labour and time demands. High-throughput somatic gene transfer techniques, principally involving the stereotaxic injection of hypothalamic neuronal groups with replication-deficient adenoviral vectors, are now being developed that obviate these difficulties, and which enable the robust, long-lasting expression of biologically active proteins in vasopressin and oxytocin MCNs. [source] Molecular characterization of the G,-globin-Tag transgenic mouse model of hormone refractory prostate cancer: Comparison to human prostate cancer,THE PROSTATE, Issue 6 2010Alfonso Calvo Abstract BACKGROUND Prostate cancer (PrCa) has a high incidence in Western countries and at present, there is no cure for hormone refractory prostate cancer. Transgenic mouse models have proven useful for understanding mechanisms of prostate carcinogenesis. The characterization of genetically modified mouse PrCa models using high-throughput genomic analyses provides important information to guide appropriate experiment applications for such model. METHODS We have analyzed the transcriptome of the hormone refractory and highly metastatic Fetal Globin-SV40/T-antigen (G,-globin-Tag) transgenic mouse model for PrCa compared to normal mouse prostate tissue. Gene expression patterns found in G,-globin-Tag mouse prostate tumors were compared with publicly available human localized and metastatic prostate tumors (GEO accession # GSE3325) through hierarchical cluster analysis, Pearson's rank correlation coefficient, and Self Organizing Feature Maps (SOM) analyses. RESULTS G,-globin-Tag tumors clustered closely with human metastatic tumors and gene expression patterns had a significant correlation (P,<,0.01), unlike human localized primary tumors (P,>,0.6). Bioinformatic analyses identified deregulated genetic pathways and networks in G,-globin-Tag tumors, which displayed similarities to alterations in human PrCa. Changes in the expression of genes involved in DNA replication and repair (Rb1, p53, Myc, PCNA, DNMT3A) and growth factor signaling pathways (TGF,2, ERK1/2, NRas, and Notch1) are deregulated in the G,-globin-Tag tumors, suggesting their key role in the oncogenic process. Identification of an enrichment of putative binding sites for transcription factors revealed eight transcription factors that may be important in G,-globin-Tag carcinogenesis, including SP1, NF-Y, CREB, Elk1, and E2F. Novel genes related to microtubule regulation were also identified in G,-globin-Tag tumors as potentially important candidate targets for PrCa. Overexpression of stathmin-1, whose expression was increased in human metastatic prostate tumors, was validated in G,-globin-Tag tumors by immunohistochemistry. This protein belongs to the SV40/T-antigen cancer signature identified in previous studies in prostate, breast, and lung cancer mouse models. CONCLUSIONS Our results show that the G,-globin-Tag model for hormone refractory PrCa shares important features with aggressive, metastatic human PrCa. Given the role of stathmin-1 in the destabilization of microtubles and taxane resistance, the G,-globin-Tag model and other SV40/T-antigen driven transgenic models may be useful for testing potential therapies directed at stathmin-1 in human prostate tumors. Prostate 70: 630,645, 2010. Published 2010 Wiley-Liss, Inc. [source] Iron Absorption: Biochemical and Molecular Insights into the Importance of Iron Species for Intestinal UptakeBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2002Piero Cremonesi Redox chemistry of iron is particularly important in iron metabolism, both as a potential source of toxic intermediates and as an essential requirement for efficient iron transport. The initial step in iron absorption (uptake from lumen to mucosa) is particularly important and several pathways involving Fe(III) reduction or transport and Fe(II) transport have been identified. Novel genes associated with iron uptake include Dcytb, a putative iron-regulated reductase and DMT1, a Fe(II) carrier in the brush border membrane. Other mechanisms may also operate, however. We review the recent findings and apply this to understanding the absorption of Fe(III) pharmaceuticals. [source] LRRN6A/LERN1 (leucine-rich repeat neuronal protein 1), a novel gene with enriched expression in limbic system and neocortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2003Laura Carim-Todd Abstract Human chromosome 15q24-q26 is a very complex genomic region containing several blocks of segmental duplications to which susceptibility to anxiety disorders has been mapped (Gratacos et al., 2001, Cell, 106, 367,379; Pujana et al., 2001, Genome Res., 11, 98,111). Through an in silico gene content analysis of the 15q24-q26 region we have identifie1d a novel gene, LRRN6A (leucine-rich repeat neuronal 6A), and confirmed its location to the centromeric end of this complex region. LRRN6A encodes a transmembrane leucine-rich repeat protein, LERN1 (leucine-rich repeat neuronal protein 1), with similarity to proteins involved in axonal guidance and migration, nervous system development and regeneration processes. The identification of homologous genes to LRRN6A on chromosomes 9 and 19 and the orthologous genes in the mouse genome and other organisms suggests that LERN proteins constitute a novel subfamily of LRR (leucine-rich repeat)-containing proteins. The LRRN6A expression pattern is specific to the central nervous system, highly and broadly expressed during early stages of development and gradually restricted to forebrain structures as development proceeds. Expression level in adulthood is lower in general but remains stable and significantly enriched in the limbic system and cerebral cortex. Taken together, the confirmation of LRRN6A's expression profile, its predicted protein structure and its similarity to nervous system-expressed LRR proteins with essential roles in nervous system development and maintenance suggest that LRRN6A is a novel gene of relevance in the molecular and cellular neurobiology of vertebrates. [source] Polymorphisms located in the region containing BHMT and BHMT2 genes as maternal protective factors for orofacial cleftsEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 4 2010Adrianna Mostowska Mostowska A, Hozyasz KK, Biedziak B, Misiak J, Jagodzinski PP. Polymorphisms located in the region containingBHMTandBHMT2genes as maternal protective factors for orofacial clefts. Eur J Oral Sci 2010; 118: 325,332. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci Nonsyndromic cleft lip with or without cleft palate (NCL/P) is one of the most common craniofacial malformations; however, its aetiology is still unclear. Because the effects of maternal nutrition on fetal development are well known, we decided to pursue the question of whether polymorphic variants of genes encoding enzymes involved in choline metabolism might be associated with the maternal risk of having a baby with NCL/P. Analysis of 18 single nucleotide polymorphisms (SNPs) of betaine-homocysteine methyltransferase (BHMT), betaine-homocysteine methyltransferase-2 (BHMT2), choline dehydrogenase (CHDH), choline kinase (CHKA), dimethylglycine dehydrogenase (DMGDH), choline-phosphate cytidylyltransferase A (PCYT1A), and phosphatidylethanolamine N -methyltransferase (PEMT) provided evidence that polymorphisms located in the region containing BHMT and BHMT2 were protective factors against NCL/P affected pregnancies in our population. The strongest signal was found for the SNP located in the intronic sequence of BHMT2. Women carrying two copies of the rs625879 T allele had a significantly decreased risk of having offspring with orofacial clefts. These results were significant, even after correction for multiple comparisons. Moreover, the gene,gene interaction analysis revealed a significant epistatic interaction of BHMT2 (rs673752), PEMT (rs12325817), and PCYT1A (rs712012) with maternal NCL/P susceptibility. Altogether, our study identified a novel gene, the nucleotide variants of which were be associated with a decreased risk of having a baby with NCL/P. [source] Genomic annotation and transcriptome analysis of the zebrafish (Danio rerio) hox complex with description of a novel member, hoxb13aEVOLUTION AND DEVELOPMENT, Issue 5 2005M. Corredor-Adámez Summary The zebrafish (Danio rerio) is an important model in evolutionary developmental biology, and its study is being revolutionized by the zebrafish genome project. Sequencing is at an advanced stage, but annotation is largely the result of in silico analyses. We have performed genomic annotation, comparative genomics, and transcriptional analysis using microarrays of the hox homeobox-containing transcription factors. These genes have important roles in specifying the body plan. Candidate sequences were located in version Zv4 of the Ensembl genome database by TBLASTN searching with Danio and other vertebrate published Hox protein sequences. Homologies were confirmed by alignment with reference sequences, and by the relative position of genes along each cluster. RT-PCR using adult Tübingen cDNA was used to confirm annotations, to check the genomic sequence and to confirm expression in vivo. Our RT-PCR and microarray data show that all 49 hox genes are expressed in adult zebrafish. Significant expression for all known hox genes could be detected in our microarray analysis. We also find significant expression of hox8 paralogs and hoxb7a in the anti-sense direction. A novel gene, D. rerio hoxb13a, was identified, and a preliminary characterization by in situ hybridization showed expression at 24 hpf at the tip of the developing tail. We are currently characterizing this gene at the functional level. We argue that the oligo design for microarrays can be greatly enhanced by the availability of genomic sequences. [source] Transcriptional regulation of ASK/Dbf4 in cutaneous melanoma is dependent on E2F1EXPERIMENTAL DERMATOLOGY, Issue 12 2008Sandeep Nambiar Background:, Melanoma is a complex genetic disease, the management of which will require an in-depth understanding of the biology underlying its initiation and progression. Recently, we have reported the differential regulation of a novel gene, namely ASK/Dbf4, in melanoma and suggested upregulation of ASK/Dbf4 as a novel molecular determinant with prognostic relevance that confers a proliferative advantage in cutaneous melanoma. As trans -acting factor binding is fundamental to understand the regulation of gene expression, this study focuses on characterization of the specific transcriptional regulation of ASK/Dbf4 in melanoma. Objective:, We investigated whether ASK/Dbf4 is a transcriptional target of the important cell cycle regulator E2F1 in melanoma. Results:, As evidenced by gel supershift assays on nuclear extracts from various melanoma cell lines (SK-MEL-28, MV3, M13, A375 and BLM), E2F1 bound to the ASK/Dbf4 minimal promoter (MP). In addition, cisplatin-mediated abrogation of E2F1 binding to the ASK/Dbf4 MP resulted in a transcriptional decrease in ASK/Dbf4. Further, the current study also demonstrated that ASK/Dbf4 regulation was refractory to UVB, a well-known risk factor for melanoma. Conclusions:, In summary, our study not only elucidated that ASK/Dbf4, a novel cell survival gene in melanoma was transcriptionally regulated by E2F1, but also that the induction of ASK/Dbf4 was refractory to UVB exposure suggesting that its upregulation was not an early event in melanomagenesis. [source] Identification and characterization of a novel transcriptional regulator, MatR, for malonate metabolism in Rhizobium leguminosarum bv. trifoliiFEBS JOURNAL, Issue 24 2000Hwan Young Lee A novel gene, matR, located upstream of matABC, transcribed in the opposite direction, and encoding a putative regulatory protein by sequence analysis was discovered from Rhizobium leguminosarum bv. trifolii. The matA, matB, and matC genes encode malonyl-CoA decarboxylase, malonyl-CoA synthetase, and a presumed malonate transporter, respectively. Together, these enzymes catalyze the uptake and conversion of malonate to acetyl-CoA. The deduced amino-acid sequence of matR showed sequence similarity with GntR from Bacillus subtilis in the N-terminal region encoding a helix-turn-helix domain. Electrophoretic mobility shift assay indicated that MatR bound to a fragment of DNA corresponding to the mat promoter region. The addition of malonate or methylmalonate increased the association of MatR and DNA fragment. DNase I footprinting assays identified a MatR binding site encompassing 66 nucleotides near the mat promoter. The mat operator region included an inverted repeat (TCTTGTA/TACACGA) centered ,46.5 relative to the transcription start site. Transcriptional assays, using the luciferase gene, revealed that MatR represses transcription from the mat promoter and malonate alleviates MatR-mediated repression effect on the expression of Pmat -luc+ reporter fusion. [source] A novel gene, ecl1+, extends the chronological lifespan in fission yeastFEMS YEAST RESEARCH, Issue 4 2008Hokuto Ohtsuka Abstract We have identified a novel gene from Schizosaccharomyces pombe that we have named ecl1+ (extender of the chronological lifespan). When ecl1+ is provided on a high-copy number plasmid, it extends the viability of both the ,sty1 MAP kinase mutant and the wild-type cells after entry into the stationary phase. ecl1+ encodes an 80-amino acid polypeptide that had not been annotated in the current database. The ecl1+ -mRNA increases transiently when the growth phase is changed from the log phase to the stationary phase. The Ecl1 protein is localized in the nucleus. Calorie restriction extends the chronological lifespan of wild-type and ,ecl1 cells but not ecl1+ -overproducing cells. The ,pka1 mutant shows little, if any, additional extension of viability when Ecl1 is overproduced. The ste11+ gene that is negatively controlled by Pka1 is up regulated when Ecl1 is overproduced. From these results we propose that the effect of Ecl1 overproduction may be mainly linked to and negatively affects the Pka1-dependent pathway. [source] Wilms tumor genetics: Mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumorsGENES, CHROMOSOMES AND CANCER, Issue 6 2008E. Cristy Ruteshouser Wilms tumor is genetically heterogeneous, and until recently only one Wilms tumor gene was known, WT1 at 11p13. However, WT1 is altered in only ,20% of Wilms tumors. Recently a novel gene, WTX at Xq11.1, was reported to be mutated in Wilms tumors. No overlap between tumors with mutations in WTX and WT1 was noted, suggesting that WT1 and WTX mutations could account for the genetic basis of roughly half of Wilms tumors. To assess the frequency of WTX mutations and their relationship to WT1 mutations in a larger (n = 125) panel of Wilms tumors which had been thoroughly assessed for mutations in WT1, we conducted a complete mutational analysis of WTX that included sequencing of the entire coding region and quantitative PCR to identify deletions of the WTX gene. Twenty-three (18.4%) tumors carried a total of 24 WTX mutations, a lower WTX mutation frequency than that previously observed. Surprisingly, we observed an equivalent frequency of WTX mutations in tumors with mutations in either or both WT1 and CTNNB1 (20.0%) and tumors with no mutation in either WT1 or CTNNB1 (17.5%). WTX has been reported to play a role in the WNT/,-catenin signaling pathway, and, interestingly, WTX deletion/truncation mutations appeared to be rare in tumors carrying exon 3 mutations of CTNNB1, encoding ,-catenin. Our findings indicate that WT1 and WTX mutations occur with similar frequency, that they partially overlap in Wilms tumors, and that mutations in WT1, WTX, and CTNNB1 underlie the genetic basis of about one-third of Wilms tumors. © 2008 Wiley-Liss, Inc. [source] Chromosome 8 BAC array comparative genomic hybridization and expression analysis identify amplification and overexpression of TRMT12 in breast cancer,GENES, CHROMOSOMES AND CANCER, Issue 7 2007Virginia Rodriguez Genomic changes in chromosome 8 are commonly observed in breast cancer cell lines and tumors. To fine map such genomic changes by comparative genomic hybridization (CGH), a high resolution (100 kb) chromosome 8 array that can detect single copy changes was developed using Phi29 DNA polymerase amplified BAC (bacterial artificial chromosome) DNA. The BAC array CGH resolved the two known amplified regions (8q21 and 8q24) of a breast cancer cell line (SKBR3) into nine separate regions including six amplicons and three deleted regions, all of which were verified by Fluorescence in situ hybridization. The extent of the gain/loss for each region was validated by qPCR. CGH was performed with a total of 8 breast cancer cell lines, and common regions of genomic amplification/deletion were identified by segmentation analysis. A 1.2-Mb region (125.3,126.5 Mb) and a 1.0-Mb region (128.1,129.1 Mb) in 8q24 were amplified in 7/8 cell lines. A global expression analysis was performed to evaluate expression changes associated with genomic amplification/deletion: a novel gene, TRMT12 (at 125.5 Mb), amplified in 7/8 cell lines, showed highest expression in these cell lines. Further analysis by RT-qPCR using RNA from 30 breast tumors showed that TRMT12 was overexpressed >2 fold in 87% (26/30) of the tumors. TRMT12 is a homologue of a yeast gene encoding a tRNA methyltransferase involved in the posttranscriptional modification of tRNAPhe, and exploring the biological consequence of its altered expression, may reveal novel pathways in tumorigenesis. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. Published 2007 Wiley-Liss, Inc. [source] Disruption of a novel gene, DIRC3, and expression of DIRC3-HSPBAP1 fusion transcripts in a case of familial renal cell cancer and t(2;3)(q35;q21)GENES, CHROMOSOMES AND CANCER, Issue 2 2003Daniëlle Bodmer Previously, we identified a family with renal cell cancer and a t(2;3)(q35;q21). Positional cloning of the chromosome 3 breakpoint led to the identification of a novel gene, DIRC2, that spans this breakpoint. Here we have characterized the chromosome 2 breakpoint in detail and found that another novel gene, designated DIRC3, spans this breakpoint. In addition, we found that the first two exons of DIRC3 can splice to the second exon of HSPBAP1, a JmjC-Hsp27 domain gene that maps proximal to the breakpoint on chromosome 3. This splice results in the formation of DIRC3-HSPBAP1 fusion transcripts. We propose that these fusion transcripts may affect normal HSPBAP1 function and concomitant chromatin remodeling and/or stress response signals within t(2;3)(q35;q21)-positive kidney cells. As a consequence, familial renal cell cancer may develop. © 2003 Wiley-Liss, Inc. [source] A novel gene, MDS2, is fused to ETV6/TEL in a t(1;12)(p36.1;p13) in a patient with myelodysplastic syndromeGENES, CHROMOSOMES AND CANCER, Issue 1 2002María D. Odero ETV6/TEL is the first transcription factor identified that is specifically required for hematopoiesis within the bone marrow. This gene has been found to have multiple fusion partners of which 16 have been cloned. Fluorescence in situ hybridization (FISH) analysis in a patient with myelodysplastic syndrome (MDS) revealed a t(1;12)(p36;p13) involving ETV6, with the breakpoint in this gene between exon 2 and exon 3. We report here the cloning of a novel ETV6 partner located on 1p36.1, involved in the t(1;12). 3, RACE-PCR from RNA identified a novel sequence fused to exon 2 of ETV6. Database searches localized this sequence in a bacterial artificial chromosome (BAC) mapped to 1p36 by fingerprint analysis. This result was confirmed by FISH using this BAC as probe. 5, and 3, RACE experiments with primers from this novel sequence were carried out on RNA from a healthy donor and identified a novel full-length mRNA, which we named MDS2 (myelodysplastic syndrome 2). RT-PCR experiments were performed on a panel of human cDNAs to analyze the expression pattern of this gene and they revealed four splicing variants. RT-PCR analysis showed that ETV6-MDS2, but not the reciprocal MDS2-ETV6 fusion transcript, was expressed in the bone marrow of the patient. The product of the ETV6-MDS2 fusion transcript predicts a short ETV6 protein containing the first 54 amino acids of ETV6 plus four novel amino acids, lacking both the PTN and the DNA-binding domains. Possible mechanisms to account for the development of MDS in this patient are discussed. © 2002 Wiley-Liss, Inc. [source] Age- and division-of-labour-dependent differential expression of a novel non-coding RNA, Nb-1, in the brain of worker honeybees, Apis mellifera L.INSECT MOLECULAR BIOLOGY, Issue 6 2009H. Tadano Abstract To elucidate the molecular mechanisms underlying honeybee social behaviours, we identified a novel gene, Nb-1, whose expression in the worker brain changes according to the age-dependent division of labour in normal colonies. The open reading frames contained in the Nb-1 cDNA were not conserved in the homologue of a related species, suggesting that the Nb-1 gene product is a non-coding RNA. The distribution of Nb-1- expressing cells partially overlapped that of octopamine-immunoreactive cells and neurosecretory cells, the latter of which are involved in the synthesis and secretion of juvenile hormone (JH). Octopamine and JH control worker task transition, and thus Nb-1 might be involved in task transition through the modulation of octopamine/JH synthesis and secretion. [source] Identification of a novel gene, Mblk-1, that encodes a putative transcription factor expressed preferentially in the large-type Kenyon cells of the honeybee brainINSECT MOLECULAR BIOLOGY, Issue 5 2001Hideaki Takeuchi Abstract Mushroom bodies (MBs) are considered to be involved in higher-order sensory processing in the insect brain. To identify the genes involved in the intrinsic function of the honeybee MBs, we searched for genes preferentially expressed therein, using the differential display method. Here we report a novel gene encoding a putative transcription factor (Mblk-1) expressed preferentially in one of two types of intrinsic MB neurones, the large-type Kenyon cells, which makes Mblk-1 a candidate gene involved in the advanced behaviours of honeybees. A putative DNA binding motif of Mblk-1 had significant sequence homology with those encoded by genes from various animal species, suggesting that the functions of these proteins in neural cells are conserved among the animal kingdom. [source] Expression of Mina53, a product of a Myc target gene in mouse testisINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2006MAKOTO TSUNEOKA Summary Recently we have identified a novel gene mina53 (mina), which is a direct transcriptional target of oncoprotein Myc. Mina53 protein was shown to be highly expressed in tumour cells and to play a role in cell proliferation. Here we report the expression of Mina53 in mouse testis, which contains proliferating cells and expresses many cancer-related genes. Immunohistochemical studies by using newly produced monoclonal antibody to Mina53 showed that Mina53 was expressed in the nuclei of spermatogonia. Mina53 was also expressed in meiotic prophase cells such as preleptotene, leptotene and zygotene, and weakly in early pachytene spermatocytes, but was absent in late pachytene spermatocytes, spermatids and mature sperm. The expression pattern of Mina53 was quite similar to that of proliferation cell nuclear antigen (PCNA). Using experimental cryptorchid testis, it was found that Mina53 was highly expressed in undifferentiated spermatogonia, which were PCNA-positive. These results suggest that Mina53 is prominently expressed in proliferating, undifferentiated spermatogonia, and plays a role in cell proliferation from the spermatogonial stage to the meiotic prophase in spermatogenesis, but not in meiotic divisions per se. [source] Searching for genes in diabetes and the metabolic syndromeINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2004G. A. Hitman Summary Evidence for a genetic basis for type 2 diabetes and the metabolic syndrome has been derived from studies of families, twins and populations with genetic admixture. Identification of genes associated with disease pathogenesis is now underway using techniques such as genome scanning by positional cloning and the candidate gene approach. Genome scanning in several different ethnic groups has identified chromosome regions harbouring type 2 diabetes susceptibility genes such as the novel gene, calpain 10 (CAPN10). The hepatic nuclear factor 4, (HNF4,) gene partly explains the linkage peak on chromosome 20, while the upstream transcription factor (USF1) is associated with familial combined hyperlipidaemia (FCHL) and maps close to the type 2 diabetes associated 1q peak. Peroxisome proliferator-activated receptor gamma (PPAR,) was identified as a candidate gene based on its biology. A Pro12Ala variant of this gene has been associated with an increased risk of type 2 diabetes. Many genes accounting for monogenic forms of diabetes have been identified , such as maturity onset diabetes of the young (MODY); glucokinase (GCK) and HNF1, mutations being the most common causes of MODY. GCK variants result in ,mild' diabetes or impaired glucose tolerance (IGT) and relatively few cardiovascular complications, while HNF1,- associated MODY is more typical of type 2 diabetes, frequently being treated with sulphonylureas or insulin and resulting in microvascular complications. Testing for single gene disorders associated with type 2 diabetes and obesity may determine cause, prognosis and appropriate treatment; however, for the more common polygenic diseases this is not the case. In type 2 diabetes, molecular genetics has the potential to enhance understanding of disease pathogenesis, and help formulate preventative and treatment strategies. [source] Identification and Gene Mapping of a Novel Mutant supernumerary lodicules (snl) in RiceJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 3 2010Nan Wang In order to gain a better understanding of rice flower development, a rice flower mutant supernumerary lodicules (snl), which was identified from ethyl methane sulfonate (EMS)-treated Jinhui10 (Oryza sativa L. ssp. indica) was used in the present study. In the snl mutant, the palea obtained lemma identity, additional glume-like organs formed, lodicules increased and elongated, stamens decreased, and a few aberrant carpels formed. These phenotypes suggest that SNL is involved in the entire rice flower development. SNL was mapped between two simple sequence repeat markers RM3512 and RM1342 on chromosome 2, an approximate 800 kb region, and it co-segregated with SSR215. We conclude that SNL is a novel gene involved in flower development in rice. The present study will be useful for further cloning of the SNL gene, which will contribute to the elucidation of rice flower development. [source] Novel putative nonprotein-coding RNA gene from 11q14 displays decreased expression in brains of patients with schizophreniaJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2003Oxana O. Polesskaya Abstract A modified method of differential display was employed to identify a novel gene (named PSZA11q14), the expression of which was reduced in brains from patients with schizophrenia. Decreased expression of PSZA11q14 was identified initially in Brodmann's area (BA) 21 from a small group of patients with schizophrenia (n = 4) and normal controls (n = 6) and was confirmed subsequently using independent RT-PCR assay in BA 21, 22, and 9, and in hippocampus from a larger group of patients with schizophrenia (n = 36) and controls (n = 35). PSZA11q14 is located on chromosome 11q14, an area shown previously to co-segregate with schizophrenia and related disorders in several families. Decreased expression of PSZA11q14 in patients with schizophrenia and its location on 11q14 provide converging lines of evidence indicating that PSZA11q14 may be involved in at least some cases of schizophrenia. PSZA11q14 shows no significant homology with any known gene. It has no introns and produces two RNA transcripts of ,4.5 and ,7.0 kb. The largest open reading frame (ORF) in the PSZA11q14 transcripts may potentially encode for a short polypeptide of 71 amino acids. High frequency of rare codons, the short size of this ORF, and low homology with mouse sequences, however, indicate that PSZA11q14 may instead represent a novel member of a family of nonprotein-coding RNA genes that are not translated and that function at the RNA level. PSZA11q14 is located within the first intron of the DLG-2 gene and transcribed in the opposite direction to DLG-2. These results suggest that PSZA11q14 may be considered a candidate gene for schizophrenia acting as an antisense regulator of DLG-2, which controls assembling functional N -methyl- D -aspartate (NMDA) receptors. © 2003 Wiley-Liss, Inc. [source] TLR-related pathway analysis: novel gene,gene interactions in the development of asthma and atopyALLERGY, Issue 2 2010N. E. Reijmerink To cite this article: Reijmerink NE, Bottema RWB, Kerkhof M, Gerritsen J, Stelma FF, Thijs C, van Schayck CP, Smit HA, Brunekreef B, Koppelman GH, Postma DS. TLR-related pathway analysis: novel gene,gene interactions in the development of asthma and atopy. Allergy 2010; 65: 199,207. Abstract Background:, The toll-like receptor (TLR)-related pathway is important in host defence and may be crucial in the development of asthma and atopy. Numerous studies have shown associations of TLR-related pathway genes with asthma and atopy phenotypes. So far it has not been investigated whether gene,gene interactions in this pathway contribute to atopy and asthma development. Methods:, One hundred and sixty-nine haplotype tagging single nucleotide polymorphisms (SNPs) of 29 genes (i.e. membrane and intracellular receptors, TLR4 or lipopolysaccharide-binding/facilitating proteins, adaptors, interleukin-1 receptor associated kinases, kinases, chaperone molecules, transcription factors and inhibitors) were analysed for single- and multilocus associations with atopy [total and specific immunglobulin E (IgE) at 1,2 and 6,8 years] and asthma (6,8 years). A total of 3062 Dutch children from the birth cohorts PIAMA, PREVASC and KOALA (Allergenic study) were investigated. Chi-squared test, logistic regression and the data mining approach multifactor dimensionality reduction method (MDR) were used in analysis. Results:, Several genes in the TLR-related pathway were associated with atopy and/or asthma [e.g. IL1RL1, BPI, NOD1, NOD2 and MAP3K7IP1]. Multiple, single associations were found with the phenotypes under study. MDR analysis showed novel, significant gene,gene interactions in association with atopy and asthma phenotypes (e.g. IL1RL1 and TLR4 with sIgE to indoor allergens and IRAK1, NOD1 and MAP3K7IP1 with asthma). Interestingly, gene,gene interactions were identified with SNPs that did not have an effect on their own. Conclusion:, Our unbiased approach provided suggestive evidence for interaction between several TLR-related pathway genes important in atopy and/or asthma development and pointed to novel genes. [source] A novel member of the glycosyltransferase family, ,3Gn-T2, highly downregulated in invasive human bladder transitional cell carcinomasMOLECULAR CARCINOGENESIS, Issue 2 2001Irina Gromova Abstract Differential display reverse transcription (DDRT),polymerase chain reaction (PCR) was used to compare the transcriptomes of invasive and noninvasive fresh human bladder transitional cell carcinomas. A differentially expressed novel gene sharing structural similarity with the human ,3-galactosyltransferase family, ,-1,3- N -acetylglucosaminyltransferase-T2 (,3Gn-T2), was identified. The full-length ,3Gn-T2 cDNA, containing a complete open reading frame of 1193 bp, was cloned and sequenced. ,3Gn-T2 exhibited 29,41% homology to the multigene ,3-galactosyltransferase family. Expression of the full-length ,3Gn-T2 cDNA in an in vitro coupled transcription/translation assay yielded a primary translation product with an apparent Mr of 46 kDa, which is in agreement with the predicted 397-amino-acid protein encoded by ,3Gn-T2. Multiple peptide alignment showed several sequence motifs corresponding to putative catalytic domains that are conserved throughout all members of the ,3-galactosyltransferase family, namely, a type II transmembrane domain, a conserved DxD motif, an N -glycosylation site, and five conserved cysteins. By RT-PCR strong downregulation of ,3Gn-T2 expression was noted in invasive human bladder transitional cell carcinomas (16 fresh biopsy samples: grade III, T2,T4) compared with their noninvasive counterparts (15 fresh biopsies: grade II, Ta), suggesting that ,3Gn-T2 may be involved in cancer progression. © 2001 Wiley-Liss, Inc. [source] Novel DNA binding protein SarZ contributes to virulence in Staphylococcus aureusMOLECULAR MICROBIOLOGY, Issue 6 2006Chikara Kaito Summary We previously reported that the cvfA gene is a virulence regulatory gene in Staphylococcus aureus. Here, we identified a novel gene named sarZ that acts as a multicopy suppressor of decreased haemolysin production in the cvfA deletion mutant. The amount of sarZ transcripts was decreased in the cvfA mutant. The sarZ -deletion mutant produced less haemolysin and attenuated virulence in a silkworm-infection model and a mouse-infection model. The amino acid sequence of the sarZ gene product had 19% identity with the transcription factor MarR in Escherichia coli, and the internal region contained a winged helix,turn,helix motif (wHTH), a known DNA binding domain. Purified recombinant SarZ protein had binding affinity for the promoter region of the hla gene that encodes ,-haemolysin. SarZ mutant proteins with an amino acid substitution in the N-terminal region or in the wHTH motif had significantly decreased DNA binding. The mutated sarZ genes encoding SarZ mutant proteins with a low affinity for DNA did not complement the decreased haemolysin production or the attenuated killing ability against silkworms in the sarZ mutant. These results suggest that the DNA binding activity of the SarZ protein is required for virulence in S. aureus. [source] Isolation and characterization of a novel Xenopus gene (xVAP019) encoding a DUF1208 domain containing proteinMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 12 2007Xu Zhi Ruan Abstract We have identified a novel Xenopus gene (xVAP019) encoding a DUF1208 domain containing protein. Using whole-mount in situ hybridization and RT-PCR, we found abundant xVAP019 maternal transcripts in the animal hemisphere during the cleavage stages and blastula stages. During gastrulation xVAP019 is differentially expressed with higher levels in the animal helf and the highest in marginal zone, then further expressed widely at neuronal stages with strongest signals in the prospective CNS regions and the epidermal ectoderm. Subsequently xVAP019 was expressed predominantly in the head, the eyes, the otic vesicle, branchial arches, spinal cord, notochord, somites, and tailbud. It is absent or very weak in the endoderm. Injecting a morpholino oligo complementary to xVAP019 mRNA or injecting a caped xVAP019 mRNA caused most of embryos to die during gastrulation and neurulation. Overexpression of xVAP019 mRNA also led to eye defect, shorten interocular distance, small body size and abnormal pigment formation in parts of the survival embryos. Similar effects were induced by injecting the xVAP019 human homologous gene FAM92A1. Our results suggest that xVAP019 is essential for the normal ectoderm and axis mesoderm differentiation and embryos survival. This investigation is for the first time in vivo study examining the role of this novel gene and reveals an important role of xVAP019 in embryonic development. Mol. Reprod. Dev. 74: 1505,1513, 2007. © 2007 Wiley-Liss, Inc. [source] Identification and characterization of TSAP, a novel gene specifically expressed in testis during spermatogenesisMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 9 2007Li Bin Abstract Through in silico screens, we have identified many previously uncharacterized genes that display similar expression patterns as the mouse Dazl gene, a germ line-specific marker. Here, we report the identification and characterization of one of these novel genes. TSAP gene encodes a protein with 350 amino acids and contains five ankyrin repeats and a PEST sequence motif. Furthermore, we have generated an anti-TSAP antibody and have used three different approaches (RT-PCR, in situ hybridization, and immunohistochemistry) to investigate the expression profiles of TSAP mRNAs and proteins. TSAP is specifically expressed in testis, but not in other tissues such as ovary. Within the testis, TSAP is detected 10 days after birth and is mainly expressed in spermatocytes (ST) and later stage of germ cells, but not in spermatogonia (SG) or sertoli cells. Therefore, TSAP protein likely plays a role in spermatogenesis. Mol. Reprod. Dev. 74: 1141,1148, 2007. © 2007 Wiley-Liss, Inc. [source] Testicular protein Spag5 has similarity to mitotic spindle protein Deepest and binds outer dense fiber protein Odf1MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2001Xueping Shao Abstract Outer dense fibers (ODF) and the fibrous sheath (FS) are major cytoskeletal structures in the mammalian sperm tail. The molecular mechanisms underlying their morphogenesis along the axoneme or their function are poorly understood. Recently, we reported the cloning and characterization of Odf2, a major ODF protein, and Spag4, an axoneme-binding protein, by virtue of their strong interaction with Odf1, the 27 kDa major ODF protein. We proposed a crucial role for leucine zippers in molecular interactions during sperm tail morphogenesis. Here we report the cloning and characterization of a novel gene, Spag5, which encodes a 200 kDa testicular protein that interacts strongly with Odf1. Spag5 is transcribed and translated in pachytene spermatocytes and spermatids. It bears 73% similarity with the mitotic spindle protein Deepest of unknown function. We identified two putative leucine zippers in the C-terminal part of the Spag5 protein, the downstream one of which is involved in interaction with Odf1. Interestingly, these motifs are present in Deepest. These results highlight the importance of the leucine zipper in sperm tail protein interactions. Mol. Reprod. Dev. 59: 410,416, 2001. © 2001 Wiley-Liss, Inc. [source] Origin of the Vertebrate Visual Cycle: III.PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2006-Monooxygenase Homologues in Ciona intestinalis, -carotene 1, Distinct Distribution of RPE6 We previously identified three genes that encode putative visual cycle proteins that are homologues of retinal G-protein coupled receptor (Ci-opsin3), cellular retinaldehyde-binding protein (Ci-CRALBP) and ,-carotene 15,15,-monooxygenase (Ci-BCO) in the ascidian Ciona intestinalis. Ci-opsin3 and Ci-CRALBP are localized in both ocellus photoreceptor cells and surrounding non-photoreceptor cells in the brain vesicle of the larva. In the present study, we investigated the possible role and evolutionary origin of the BCO/RPE65 family in the visual cycle by analyzing Ci-BCO localization by immunohistochemistry and by identifying a novel gene that encodes a homologue of retinal pigment epithelium,specific 65 kDa protein (Ci-RPE65) in C. intestinalis. In situ hybridization and expressed sequence tag (EST) profiles consistently suggest that Ci-RPE65 is not significantly expressed in the ocellus and brain vesicle of the larva. Ci-RPE65 is expressed in the neural complex, a photoreceptor organ of the adult ascidian, at a level comparable to that of Ci-opsin3 and Ci-CRALBP. Ci-RPE65 is also expressed in various adult tissues, including the gill, body wall and intestine, suggesting that Ci-RPE65 plays a role in addition to that in the visual cycle. In contrast, Ci-BCO is predominantly localized in ocellus photoreceptor cells of the larva. The larval visual cycle seems to use Ci-opsin3 as a photoisomerase. Our results also suggest that the RPE65-dependent visual cycle is used in the adult photoreceptors of a primitive chordate. [source] | |||||||||||||||||||||||||||||||||||||