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Genes Important (gene + important)
Selected AbstractsTumors Associated With Oncogenic Osteomalacia Express Genes Important in Bone and Mineral MetabolismJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2002Suzanne M. Jan De Beur Abstract Oncogenic osteomalacia (OOM) is associated with primitive mesenchymal tumors that secrete phosphaturic factors resulting in low serum concentrations of phosphate and calcitriol, phosphaturia, and defective bone mineralization. To identify overexpressed genes in these tumors, we compared gene expression profiles of tumors resected from patients with OOM and histologically similar control tumors using serial analysis of gene expression (SAGE). Three hundred and sixty-four genes were expressed at least twofold greater in OOM tumors compared with control tumors. A subset of 67 highly expressed genes underwent validation with an extended set of OOM and control tumors using array analysis or reverse-transcription polymerase chain reaction (RT-PCR). Ten of these validated genes were consistently overexpressed in all OOM tumors relative to control tumors. Strikingly, genes with roles in bone matrix formation, mineral ion transport, and bone mineralization were highly expressed in the OOM tumors. [source] Chromosomal antioxidant genes have metal ion-specific roles as determinants of bacterial metal toleranceENVIRONMENTAL MICROBIOLOGY, Issue 10 2009Joe J. Harrison Summary Microbiological metal toxicity involves redox reactions between metal species and cellular molecules, and therefore, we hypothesized that antioxidant systems might be chromosomal determinants affecting the susceptibility of bacteria to metal toxicity. Here, survival was quantified in metal ion-exposed planktonic cultures of several Escherichia coli strains, each bearing a mutation in a gene important for redox homeostasis. This characterized ,250 gene,metal combinations and identified that sodA, sodB, gor, trxA, gshA, grxA and marR have distinct roles in safeguarding or sensitizing cells to different toxic metal ions (Cr2O72,, Co2+, Cu2+, Ag+, Zn2+, AsO2,, SeO32, or TeO32,). To shed light on these observations, fluorescent sensors for reactive oxygen species (ROS) and reduced thiol (RSH) quantification were used to ascertain that different metal ions exert oxidative toxicity through disparate modes-of-action. These oxidative mechanisms of metal toxicity were categorized as involving ROS and thiol-disulfide chemistry together (AsO2,, SeO32,), ROS predominantly (Cu2+, Cr2O72,) or thiol-disulfide chemistry predominantly (Ag+, Co2+, Zn2+, TeO32,). Corresponding to this, promoter- luxCDABE fusions showed that toxic doses of different metal ions up- or downregulate the transcription of gene sets marking distinct pathways of cellular oxidative stress. Altogether, our findings suggest that different metal ions are lethal to cells through discrete pathways of oxidative biochemistry, and moreover, indicate that chromosomally encoded antioxidant systems may have metal ion-specific physiological roles as determinants of bacterial metal tolerance. [source] Heritability, correlations and in silico mapping of locomotor behavior and neurochemistry in inbred strains of miceGENES, BRAIN AND BEHAVIOR, Issue 4 2005T. R. Mhyre The midbrain dopamine system mediates normal and pathologic behaviors related to motor activity, attention, motivation/reward and cognition. These are complex, quantitative traits whose variation among individuals is modulated by genetic, epigenetic and environmental factors. Conventional genetic methods have identified several genes important to this system, but the majority of factors contributing to the variation remain unknown. To understand these genetic and environmental factors, we initiated a study measuring 21 behavioral and neurochemical traits in 15 common inbred mouse strains. We report trait data, heritabilities and genetic and non-genetic correlations between pheno-types. In general, the behavioral traits were more heritable than neurochemical traits, and both genetic and non-genetic correlations within these trait sets were high. Surprisingly, there were few significant correlations between the behavioral and the individual neurochemical traits. However, striatal serotonin and one measure of dopamine turnover (DOPAC/DA) were highly correlated with most behavioral measures. The variable accounting for the most variation in behavior was mouse strain and not a specific neurochemical measure, suggesting that additional genetic factors remain to be determined to account for these behavioral differences. We also report the prospective use of the in silico method of quantitative trait loci (QTL) analysis and demonstrate difficulties in the use of this method, which failed to detect significant QTLs for the majority of these traits. These data serve as a framework for further studies of correlations between different midbrain dopamine traits and as a guide for experimental cross designs to identify QTLs and genes that contribute to these traits. [source] Genetic analysis of collagen-induced arthritis in rats: a polygenic model for rheumatoid arthritis predicts a common framework of cross-species inflammatory/autoimmune disease lociIMMUNOLOGICAL REVIEWS, Issue 1 2001Marie M. Griffiths Summary: Collagen-induced arthritis (CIA) is a useful model for dissecting the genetic patterns underlying susceptibility to rheumatoid arthritis (RA) and related chronic/inflammatory autoimmune diseases. CIA exhibits three phenotypes characteristic of autoimmune disease pathogenesis: abnormal levels of immune reactivity to self antigens; chronic inflammation of target organs expressing that specific autoantigen; activation and direct participation of invading mononuclear cells and resident tissue fibroblasts in organ damage. Over 25 different quantitative trait loci (QTL) regulating arthritis severity and autoantibody in rats with CIA are mapped. QTL-congenic strains show that certain CIA,QTLs can modulate arthritis independently. These monogenic models are proving to be highly informative for fine mapping and function studies, revealing gender effects and evidence of gene clusters. Recent genome scans of RA populations identified RA-susceptibility loci in chromosome regions homologous to rat chromosomal segments housing CIA,QTLs. Also, CIA,QTLs frequently co-localize with susceptibility QTLs mapped in other rat arthritis models induced with non-immunogenic adjuvant oils and/or in rat autoimmune models of multiple sclerosis and diabetes. Common autoimmunity genes and inflammation genes important to several human diseases are likely being detected in the various rat disease models. Continued dissection of the genetic underpinnings of rat arthritis models should provide candidate genes for investigation in human patients and lead to a clearer understanding of the complex genetics of RA. [source] Ets-1 immunohistochemical expression in non-melanoma skin carcinomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2004Connie A. Keehn Background:, Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in non-melanoma skin carcinomas. Design:, A series of 26 primary cutaneous skin lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle Upon Tyne, England, UK) was scored by an average of the mean labeling intensity (MLI), where no nuclear staining = 0, weak nuclear staining = 1, moderate nuclear staining = 2, and strong nuclear staining = 3. Results:, All basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC) cases exhibited negative nuclear staining, for an average MLI of 0. Keratoacanthomas, squamous cell carcinoma in situ (SIS), and well-differentiated squamous cell carcinomas (SCCs) exhibited negative to weak nuclear staining, for an average MLI of 0.4 ± 0.3. Moderately differentiated SCCs exhibited moderate nuclear staining, for an average MLI of 1.8 ± 0.6. Poorly differentiated SCCs and metastatic SCCs exhibited very strong nuclear staining, with an average MLI of 2.8 ± 0.2. Conclusions:, Ets-1 is not expressed in cutaneous BCC or MCC and is weakly expressed in SIS and forms of well-differentiated SCC. Although the intensity of Ets-1 immunostaining distinguished between well-differentiated and poorly differentiated SCC (p < 0.0001), it failed to discriminate between in situ and well-differentiated SCCs. The preliminary data suggests Ets-1 may be important in the pathogenesis of invasive SCC. [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 major breakpoint cluster domain in murine radiation-induced acute myeloid leukemia,MOLECULAR CARCINOGENESIS, Issue 2 2002Rosemary Finnon Abstract Cytogenetic and molecular studies have provided evidence of the clustering of chromosome 2 deletion breakpoints in radiation-induced murine acute myeloid leukemia (AML). Moreover, clustering occurs in at least two fragile domains rich in telomere-like arrays. Here we describe a physical map of the distal breakpoint cluster and confirm the presence of inverted head-to-head telomeric sequence arrays. These potentially recombinogenic sequences were not, however, the direct focus for post-irradiation chromosome breakage in AML. Instead, the two arrays bordered a 2.5-kb sequence with properties expected of a nuclear matrix attachment region (MAR). The putative MAR co-localized in the fragile domain with genes important to the hemopoietic system (leukocyte tyrosine kinase, zinc finger protein 106, erythrocyte protein band 4.2, and ,2 -microglobulin (,2m)); the ,2m subdomain was a particular focus of breakage. On the basis of these and other data, we suggest that AML-associated chromosome 2 fragility in the mouse is a consequence of domain-specific fragility in genomic domains containing numerous genes critical to the hemopoietic system. Copyright © Crown Copyright 2002. Recorded with the permission of the controller of Her Majesty's Stationery Office. Published by Wiley-Liss, Inc. [source] Expression and chromosomal organization of mouse meiotic genesMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2010Hiba Waldman Ben-Asher Microarray technology which enables large scale analysis of gene expression and thus comparison between transcriptomes of different cell types, cells undergoing different treatments or cells at different developmental stages has also been used to study the transcriptome involved with spermatogenesis. Many new germ cell-specific genes were determined, and the resulting genes were classified according to different criteria. However, the biological significance of these classifications and their clustering according to developmental transcriptional patterns during spermatogenesis have not yet been addressed. In this study we utilized mouse testicular transcriptome analysis at five distinct post-natal ages (Days 7, 10, 12, 14, and 17), representing distinct meiotic stages, in an attempt to better understand the biological significance of genes clustered into similar expression patterns during this process. Among 790 sequences that showed an expression level change of twofold or more in any of the five key stages that were monitored, relative to the geometric average of all stages, about 40% peaked and about 30% were specifically suppressed at post-natal day 14 (representing the early pachytene stage of spermatocytes), reflecting tight transcriptional regulation at this stage. We also found that each of the six main transcription clusters that were determined was characterized by statistically significant representation of genes related to specific biological processes. Finally, our results indicated that genes important for meiosis are not randomly distributed along the mouse genome but rather preferentially located on specific chromosomes, suggesting for the first time that chromosomal location might be a regulating factor of meiotic gene expression. Mol. Reprod. Dev. 77: 241,248, 2010. © 2009 Wiley-Liss, Inc. [source] Changes of maternal transcripts in oocytes from persistent follicles in cattleMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2007Brandon M. Lingenfelter Abstract A high incidence of early embryonic loss is associated with prolonged dominance of follicles. The objective of the present experiment was to determine if persistence of a follicle resulted in alterations in mRNA expression of important genes in the oocyte. Cows were assigned to four groups: growing follicles on day 6 (G0h) or day 8 (G48h) and persistent follicles on day 13 (P0h) or day 15 (P48h) of the estrous cycle (estrus,=,day 0). All cows were super-stimulated on day 1,4. Cows in G48h, P0h, and P48h groups received 25 mg prostaglandin (PG) F2, on day 6. Cows in P0h and P48h groups received progesterone from CIDR-B devices on day 5 through 13. Ovaries of cows in G0h, G48h, P0h, and P48h groups were removed on day 6, 8, 13, and 15, respectively. Oocytes were aspirated immediately after colpotomy and denuded of cumulus cells. Quantitative real-time PCR was used to measure the mRNA abundances of 10 selected genes important for early embryogenesis in oocytes obtained from growing and persistent follicles. Relative abundances of MSY2, PARN, and YY1 mRNA (P,<,0.05) were significantly lower in oocytes from persistent than from growing follicles. Oocytes from persistent follicles, however, had greater abundances of PAP and eIF-4E transcripts (P,<,0.05). The data indicate that persistence of a follicle leads to altered abundances of mRNA for genes important for regulation of transcription and protein translation in the oocyte, which could compromise development of early embryos in cows that ovulate a persistent follicle. Mol. Reprod. Dev. © 2006 Wiley-Liss, Inc. [source] Informatic and genomic analysis of melanocyte cDNA libraries as a resource for the study of melanocyte development and functionPIGMENT CELL & MELANOMA RESEARCH, Issue 3 2007Laura L. Baxter Summary As part of the RIKEN mouse encyclopedia project, two cDNA libraries were prepared from melanocyte-derived cell lines, using techniques of full-length clone selection and subtraction/normalization to enrich for rare transcripts. End sequencing showed that these libraries display over 83% complete coding sequence at the 5, end and 96,97% complete coding sequence at the 3, end. Evaluation of the libraries, derived from B16F10Y tumor cells and melan-c cells, revealed that they contain clones for a majority of the genes previously demonstrated to function in melanocyte biology. Analysis of genomic locations for transcripts revealed that the distribution of melanocyte genes is non-random throughout the genome. Three genomic regions identified that showed significant clustering of melanocyte-expressed genes contain one or more genes previously shown to regulate melanocyte development or function. A catalog of genes expressed in these libraries is presented, providing a valuable resource of cDNA clones and sequence information that can be used for identification of new genes important for melanocyte development, function, and disease. [source] Alpha 1 antitrypsin deficiency alleles are associated with joint dislocation and scoliosis in Williams syndrome,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2010Colleen A. Morris Abstract Elastin haploinsufficiency is responsible for a significant portion of the Williams syndrome (WS) phenotype including hoarse voice, supravalvar aortic stenosis (SVAS), hernias, diverticuli of bowel and bladder, soft skin, and joint abnormalities. All of the connective tissue signs and symptoms are variable in the WS population, but few factors other than age and gender are known to influence the phenotype. We examined a cohort of 205 individuals with WS for mutations in SERPINA1, the gene that encodes alpha-1-antitrypsin (AAT), the inhibitor of elastase. Individuals with classic WS deletions and SERPINA1 genotypes PiMS or PiMZ were more likely than those with a SERPINA1 PiMM genotype to have joint dislocation or scoliosis. However, carrier status for AAT deficiency was not correlated with presence of inguinal hernia or with presence or severity of SVAS. These findings suggest that genes important in elastin metabolism are candidates for variability in the connective tissue abnormalities in WS. © 2010 Wiley-Liss, Inc. [source] Arabidopsis proteins important for modulating defense responses to Pseudomonas syringae that secrete HopW1-1THE PLANT JOURNAL, Issue 3 2008Min Woo Lee Summary Plant infection responses result from the interaction of pathogen-derived molecules with host components. For the bacterial pathogen Pseudomonas syringae, these molecules are often effector proteins (Hops) that are injected into plant cells. P. syringae carrying hopW1-1 have restricted host range on some Arabidopsis thaliana accessions. At least two Arabidopsis genomic regions are important for the natural variation that conditions resistance to P. syringae/hopW1-1. HopW1-1 elicits a resistance response, and consequently the accumulation of the signal molecule salicylic acid (SA) and transcripts of HWI1 (HopW1-1-Induced Gene1). This work identified three HopW1-1-interacting (WIN) plant proteins: a putative acetylornithine transaminase (WIN1), a protein phosphatase (WIN2) and a firefly luciferase superfamily protein (WIN3). Importantly, WIN2 and WIN3 are partially required for HopW1-1-induced disease resistance, SA production and HWI1 expression. The requirement for WIN2 is specific for HopW1-1-induced resistance, whereas WIN3 is important for responses to several effectors. Overexpression of WIN2 or WIN3 confers resistance to virulent P. syringae, which is consistent with these proteins being defense components. Several known genes important for SA production or signaling are also partially (EDS1, NIM1/NPR1, ACD6 and ALD1) or strongly (PAD4) required for the robust resistance induced by HopW1-1, suggesting a key role for SA in the HopW1-1-induced resistance response. Finally, WIN1 is an essential protein, the overexpression of which over-rides the resistance response to HopW1-1 (and several other defense-inducing effectors), and delays SA and HWI1 induction. Thus, the WIN proteins have different roles in modulating plant defense. [source] Genetic regulation of stem cell origins in the mouse embryoCLINICAL GENETICS, Issue 2 2005A Ralston ,Stem cell' has practically become a household term, but what is a stem cell and where does it come from? Insight into these questions has come from the early mouse embryo, or blastocyst, from which three kinds of stem cells have been derived: embryonic stem (ES) cells, trophoblast stem (TS) cells, and extraembryonic endoderm (XEN) cells. These stem cells appear to derive from three distinct tissue lineages within the blastocyst: the epiblast, the trophectoderm, and the extraembryonic endoderm. Understanding how these lineages arise during development will illuminate efforts to understand the establishment and maintenance of the stem cell state and the mechanisms that restrict stem cell potency. Genetic analysis has enabled the identification of several genes important for lineage decisions in the mouse blastocyst. Among these, Oct4, Nanog, Cdx2, and Gata6 encode transcription factors required for the three lineages of the blastocyst and for the maintenance their respective stem cell types. Interestingly, genetic manipulation of several of these factors can cause lineage switching among these stem cells, suggesting that knowledge of key lineage-determining genes could help control differentiation of stem cells more generally. Pluripotent stem cells have also been isolated from the human blastocyst, but the relationship between these cells and stem cells of the mouse blastocyst remains to be explored. This review describes the genetic regulation of lineage allocation during blastocyst formation and discusses similarities and differences between mouse and human ES cells. [source] | |||||||||||||