The Conserved Transcriptome in Human and Rodent Male Gametogenesis

Total Page:16

File Type:pdf, Size:1020Kb

The Conserved Transcriptome in Human and Rodent Male Gametogenesis The conserved transcriptome in human and rodent male gametogenesis Fre´ de´ ric Chalmel*, Antoine D. Rolland†, Christa Niederhauser-Wiederkehr*, Sanny S. W. Chung‡, Philippe Demougin*, Alexandre Gattiker*, James Moore*, Jean-Jacques Patard§, Debra J. Wolgemuth‡, Bernard Je´ gou†, and Michael Primig*¶ʈ *Biozentrum and Swiss Institute of Bioinformatics, Klingelbergstrasse 50-70, CH-4056 Basel, Switzerland; †Institut National de la Sante´et de la Recherche Me´dicale U625, Group d’Etude de la Reproduction chez l’Homme et les Mammife`res, Institut Fe´de´ ratif de Recherche 140; Universite´de Rennes I, Campus de Beaulieu , F-35042 Rennes, France; ‡Columbia University Medical Center, Black Building 1613, 630 West 168th Street, New York, NY 10032; and §Centre Hospitalier Universitaire Re´gional Pontchaillou, Service d’Urologie, F-35000 Rennes, France Communicated by Ronald W. Davis, Stanford University School of Medicine, Palo Alto, CA, March 15, 2007 (received for review October 12, 2006) We report a cross-species expression profiling analysis of the Gene Ontology Consortium (20), shows that genes known or human, mouse, and rat male meiotic transcriptional program, using predicted to be important for meiosis and reproduction are enriched germ cell populations, whole gonads, and high-density significantly enriched among loci expressed in testicular cell oligonucleotide microarrays (GeneChips). Among 35% of the types (13). Thus, profiling experiments likely help identify protein-coding genes present in rodent and human genomes that factors important for the meiotic developmental pathway in both were found to be differentially expressed between germ cells and yeast (3, 4) and mammals (14). somatic controls, a key group of 357 conserved core loci was In this study, enriched mitotic, meiotic, and postmeiotic germ identified that displays highly similar meiotic and postmeiotic cells were compared with somatic Sertoli cells to select differ- patterns of transcriptional induction across all three species. Genes entially expressed mouse and rat loci. Among them, a group of known to be important for sexual reproduction are significantly conserved core genes were identified whose expression profiles enriched among differentially expressed core loci and a smaller in meiotic and postmeiotic germ cells are highly similar between group of conserved genes not detected in 17 nontesticular somatic rodents and human. Numerous potentially testis-specific loci tissues, correlating transcriptional activation and essential func- were found by comparing the transcriptional activity of differ- tion in the male germ line. Some genes implicated in the etiology entially expressed genes in testis to 17 somatic control tissues. of cancer are found to be strongly transcribed in testis, suggesting Using whole-genome arrays covering all currently annotated that these genes may play unexpected roles in sexual reproduc- genes in rodent and human genomes together with a compre- tion. Expression profiling data further identified numerous con- hensive cross-species experimental approach revealed several served genes of biological and clinical interest previously unasso- hundred novel genes likely to be involved in the mammalian ciated with the mammalian male germ line. meiotic process. A graphical display of the expression data is available from the GermOnline database (www.germonline.org) bioinformatics ͉ spermatogenesis ͉ transcriptome that can be searched for individual genes as well as groups of loci (21). Additional information, including analysis software and eiosis and gametogenesis are critical processes in the raw data, is available from the authors upon request [see Mtransmission of genetic material to subsequent genera- supporting information (SI) Results]. tions during sexual reproduction. A large number of genes Results and Discussion involved in this process have been characterized in model organisms, such as budding and fission yeast (1–4) and nema- Defining the Mammalian Testicular Expression Program. mRNA todes (5), but comparatively few essential and specifically ex- from highly enriched populations of rodent somatic Sertoli cells pressed loci are known in mammals, particularly humans (6, 7). and mitotic spermatogonia, meiotic spermatocytes and postmei- In males, mitotically growing spermatogonia develop into mei- otic round spermatids as well as isolated seminiferous tubules otic spermatocytes that give rise to haploid spermatids which and total testis samples were analyzed by using high density differentiate into mature sperm. This pathway is controlled in oligonucleotide microarrays [Fig. 1; see also SI Table 1]. Total and cRNA quality was found to be very homogenous (SI Fig. 5 part by somatic Sertoli cells that physically interact with germ a and b) and the overall reproducibility of the data was excellent cells and communicate with them by hormonal cues (for review, as shown by a distance matrix (SI Fig. 5c). The transcripts see refs. 8–11). Many of the loci required for meiotic landmark events such as recombination and gamete formation are known to be expressed only in cells capable of undergoing the process, Author contributions: F.C., A.D.R., C.N.-W., B.J., and M.P. contributed equally to this work; but the regulatory network that confers germ-line-specific tran- A.D.R., S.S.W.C., D.J.W., B.J., and M.P. designed research; A.D.R., S.S.W.C., P.D., A.G., and scription in higher eukaryotes is poorly understood, especially at J.-J.P. performed research; F.C., A.D.R., A.G., J.-J.P., D.J.W., and B.J. contributed new the mitotic and meiotic stages (12). reagents/analytic tools; F.C., A.D.R., C.N.-W., S.S.W.C., J.M., and M.P. analyzed data; and M.P. wrote the paper. Recent studies have identified a large number of genes active during gametogenesis using testicular expressed sequence tag The authors declare no conflict of interest. libraries, serial analysis of gene expression (SAGE) and microar- Freely available online through the PNAS open access option. ray profiling of enriched germ cell and testis samples from Abbreviation: GO, gene ontology. rodents (13, 14). These array studies covered approximately one ¶Present address: Institut National de la Sante´et de la Recherche Me´dicale U 625, Institut Fe´de´ ratif de Recherche 140; Universite´de Rennes I, Avenue du Ge´ne´ ral Leclerc, F-35042 third of the genes currently known to be encoded by the mouse Rennes, France. and rat genomes and showed that differentiating germ cells ʈTo whom correspondence should be addressed. E-mail: [email protected]. up-regulate hundreds of transcripts (15–17), including many that Data deposition: The data reported in this paper have been deposited in the European encode germ-line-specific products (18). Although numerous Bioinformatics Institute (EBI) ArrayExpress database, www.ebi.ac.uk/arrayexpress mRNAs have also been detected in mature human sperm, (accession no. E-TABM-130). regulation of gene expression underlying germ cell development This article contains supporting information online at www.pnas.org/cgi/content/full/ and the roles these transcripts may play during embryogenesis 0701883104/DC1. remain unclear (19). Statistical analysis, using data from the © 2007 by The National Academy of Sciences of the USA 8346–8351 ͉ PNAS ͉ May 15, 2007 ͉ vol. 104 ͉ no. 20 www.pnas.org͞cgi͞doi͞10.1073͞pnas.0701883104 Downloaded by guest on September 29, 2021 Fig. 1. Schematic representation of the mammalian testis. (a) Drawing of the testis containing seminiferous tubules and the epididymis. (b) Sertoli nurse cell associated with a mitotic spermatogonium, a meiotic pachytene spermato- cyte, and round and elongated postmeiotic spermatids. corresponding to GeneChip probe set IDs were annotated by using information provided by the GeneChip manufacturer and additional data retrieved by links to external databases (SI Fig. 6 a and b). Genes whose expression signals varied significantly between Sertoli cells, germ cells, tubules, and whole-organ controls were designated as ‘‘differentially expressed in testis’’ (DET) (this ab- breviation is also used in the BioMart query form of GermOnline). This approach identified 9,280 and 5,895 probe sets that map to 7,066 and 5,140 unique protein-coding mouse and rat genes, respectively, representing Ϸ36% of the transcripts detected by the rodent GeneChips (22, 23). The differentially expressed probe sets were further classified by using a hierarchical clustering algorithm (SI Fig. 7 a and b). Somatic Sertoli cells and mitotic spermatogonia show similar profiles, distinguishing them from meiotic spermato- Fig. 2. The core testicular transcriptome in mammals (CDET). (a) Venn diagram of conserved probesets (top number) and corresponding genes (bot- cytes and postmeiotic spermatids clustered together with tubules tom number) represented on each GeneChip. (b) Summarizes the filtration and total testis samples (top dendrogram). This finding is in and clustering procedure. (c) Heatmaps of expression patterns in four clusters agreement with earlier observations using similar rat samples (15). for three species as indicated. Numbers of probe sets and corresponding genes Subsequently, human chondrocytes and smooth vascular muscle in each expression cluster are shown at the left. Sample names are Sertoli cells cells were compared with enriched pachytene spermatocytes and (SE), spermatogonia (SG), spermatocytes (SC), spermatids (ST), tubules (TU), postmeiotic round spermatids, yielding 6,499 probe sets that cor- and total testis (TT). Human
Recommended publications
  • Peking University-Juntendo University Joint Symposium on Cancer Research and Treatment ADAM28 (A Disintegrin and Metalloproteinase 28) in Cancer Cell Proliferation and Progression
    Whatʼs New from Juntendo University, Tokyo Juntendo Medical Journal 2017. 63(5), 322-325 Peking University - Juntendo University Joint Symposium on Cancer Research and Treatment ADAM28 (a Disintegrin and Metalloproteinase 28) in Cancer Cell Proliferation and Progression YASUNORI OKADA* *Department of Pathophysiology for Locomotive and Neoplastic Diseases, Juntendo University Graduate School of Medicine, Tokyo, Japan A disintegrinandmetalloproteinase 28 (ADAM28) is overexpressedpredominantlyby carcinoma cells in more than 70% of the non-small cell lung carcinomas, showing positive correlations with carcinoma cell proliferation and metastasis. ADAM28 cleaves insulin-like growth factor binding protein-3 (IGFBP-3) in the IGF-I/IGFBP-3 complex, leading to stimulation of cell proliferation by intact IGF-I released from the complex. ADAM28 also degrades von Willebrand factor (VWF), which induces apoptosis in human carcinoma cell lines with negligible ADAM28 expression, andthe VWF digestionby ADAM28-expressing carcinoma cells facilitates them to escape from VWF-induced apoptosis, resulting in promotion of metastasis. We have developed human antibodies against ADAM28 andshown that one of them significantly inhibits tumor growth andmetastasis using lung adenocarcinoma cells. Our data suggest that ADAM28 may be a new molecular target for therapy of the patients with ADAM28-expressing non-small cell lung carcinoma. Key words: a disintegrin and metalloproteinase 28 (ADAM28), cell proliferation, invasion, metastasis, human antibody inhibitor Introduction human cancers 2). However, development of the synthetic inhibitors of MMPs andtheir application Cancer cell proliferation andprogression are for treatment of the cancer patients failed 3). modulated by proteolytic cleavage of tissue micro- On the other hand, members of the ADAM (a environmental factors such as extracellular matrix disintegrin and metalloproteinase) gene family, (ECM), growth factors andcytokines, receptors another family belonging to the metzincin gene andcell adhesionmolecules.
    [Show full text]
  • Mouse Fscn3 Conditional Knockout Project (CRISPR/Cas9)
    https://www.alphaknockout.com Mouse Fscn3 Conditional Knockout Project (CRISPR/Cas9) Objective: To create a Fscn3 conditional knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Fscn3 gene (NCBI Reference Sequence: NM_019569 ; Ensembl: ENSMUSG00000029707 ) is located on Mouse chromosome 6. 7 exons are identified, with the ATG start codon in exon 1 and the TAG stop codon in exon 6 (Transcript: ENSMUST00000031719). Exon 2 will be selected as conditional knockout region (cKO region). Deletion of this region should result in the loss of function of the Mouse Fscn3 gene. To engineer the targeting vector, homologous arms and cKO region will be generated by PCR using BAC clone RP24-176I9 as template. Cas9, gRNA and targeting vector will be co-injected into fertilized eggs for cKO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Exon 2 starts from about 9.71% of the coding region. The knockout of Exon 2 will result in frameshift of the gene. The size of intron 1 for 5'-loxP site insertion: 1817 bp, and the size of intron 2 for 3'-loxP site insertion: 839 bp. The size of effective cKO region: ~1197 bp. The cKO region does not have any other known gene. Page 1 of 7 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele 5' gRNA region gRNA region 3' 1 2 3 7 Targeting vector Targeted allele Constitutive KO allele (After Cre recombination) Legends Homology arm Exon of mouse Fscn3 cKO region loxP site Page 2 of 7 https://www.alphaknockout.com Overview of the Dot Plot Window size: 10 bp Forward Reverse Complement Sequence 12 Note: The sequence of homologous arms and cKO region is aligned with itself to determine if there are tandem repeats.
    [Show full text]
  • Ovarian Gene Expression in the Absence of FIGLA, an Oocyte
    BMC Developmental Biology BioMed Central Research article Open Access Ovarian gene expression in the absence of FIGLA, an oocyte-specific transcription factor Saurabh Joshi*1, Holly Davies1, Lauren Porter Sims2, Shawn E Levy2 and Jurrien Dean1 Address: 1Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA and 2Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA Email: Saurabh Joshi* - [email protected]; Holly Davies - [email protected]; Lauren Porter Sims - [email protected]; Shawn E Levy - [email protected]; Jurrien Dean - [email protected] * Corresponding author Published: 13 June 2007 Received: 11 December 2006 Accepted: 13 June 2007 BMC Developmental Biology 2007, 7:67 doi:10.1186/1471-213X-7-67 This article is available from: http://www.biomedcentral.com/1471-213X/7/67 © 2007 Joshi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Ovarian folliculogenesis in mammals is a complex process involving interactions between germ and somatic cells. Carefully orchestrated expression of transcription factors, cell adhesion molecules and growth factors are required for success. We have identified a germ-cell specific, basic helix-loop-helix transcription factor, FIGLA (Factor In the GermLine, Alpha) and demonstrated its involvement in two independent developmental processes: formation of the primordial follicle and coordinate expression of zona pellucida genes. Results: Taking advantage of Figla null mouse lines, we have used a combined approach of microarray and Serial Analysis of Gene Expression (SAGE) to identify potential downstream target genes.
    [Show full text]
  • Genome-Wide Analysis Reveals Selection Signatures Involved in Meat Traits and Local Adaptation in Semi-Feral Maremmana Cattle
    Genome-Wide Analysis Reveals Selection Signatures Involved in Meat Traits and Local Adaptation in Semi-Feral Maremmana Cattle Slim Ben-Jemaa, Gabriele Senczuk, Elena Ciani, Roberta Ciampolini, Gennaro Catillo, Mekki Boussaha, Fabio Pilla, Baldassare Portolano, Salvatore Mastrangelo To cite this version: Slim Ben-Jemaa, Gabriele Senczuk, Elena Ciani, Roberta Ciampolini, Gennaro Catillo, et al.. Genome-Wide Analysis Reveals Selection Signatures Involved in Meat Traits and Local Adaptation in Semi-Feral Maremmana Cattle. Frontiers in Genetics, Frontiers, 2021, 10.3389/fgene.2021.675569. hal-03210766 HAL Id: hal-03210766 https://hal.inrae.fr/hal-03210766 Submitted on 28 Apr 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License ORIGINAL RESEARCH published: 28 April 2021 doi: 10.3389/fgene.2021.675569 Genome-Wide Analysis Reveals Selection Signatures Involved in Meat Traits and Local Adaptation in Semi-Feral Maremmana Cattle Slim Ben-Jemaa 1, Gabriele Senczuk 2, Elena Ciani 3, Roberta
    [Show full text]
  • Building Bonds Between NHGRI and NICHD • NICHD Has Four ABMGG Boarded Clinical Geneticists • Drs
    Building Bonds Between NHGRI NICHD Diana W. Bianchi, M.D. Director, NICHD November 8, 2017 A Vision for NICHD’s Future What’s In a Name? NICHD 18% Other Institutes 82% Eunice Kennedy Shriver National Institute of Child Health and Human Development History of Our Mission ". We will look to the National Institute of Child Health and Human Development for a concentrated attack on the unsolved health problems of children and of mother-infant relationships. This legislation will encourage imaginative research into the complex processes of human development from conception to old age. For the first time, we will have an institute to promote studies directed at the entire life process rather than toward specific diseases or illnesses." —John F. Kennedy, October 17, 1962 My Vision for NICHD-I • Define “our brand” (what is our focus?) • Communicate the message • Listen to the Voice of the Patient • Integrate obstetrics and pediatrics research at NICHD; take the long view (DoHaD) • Advocate for personalized medicine in pediatrics, obstetrics and rehabilitative medicine My Vision for NICHD-II • Stress the importance of data science and sharing to leverage our investments • Analyze best way to identify trainees most likely to succeed • Catalyze innovation • Emphasize the “A” (for “Advice”) in the Advisory Council • Build bridges between other NIH Institutes – especially with NHGRI Ensure Representation of NICHD Populations in Trans-NIH Initiatives • Pregnant women can be enrolled in Phase I • Adults with intellectual disabilities can be enrolled once consent issues have been clarified • Children to be enrolled in Phase II Building Bonds Melissa Parisi MD PhD Medical Genetics Branch: Prenatal Genomics and Therapy Section • New Lab at NHGRI • Focus on Prenatal Treatment of Down syndrome • Incidental Findings Following Prenatal DNA Screening Building Bonds Between NHGRI and NICHD • NICHD has four ABMGG boarded clinical geneticists • Drs.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Mammalian Male Germ Cells Are Fertile Ground for Expression Profiling Of
    REPRODUCTIONREVIEW Mammalian male germ cells are fertile ground for expression profiling of sexual reproduction Gunnar Wrobel and Michael Primig Biozentrum and Swiss Institute of Bioinformatics, Klingelbergstrasse 50-70, 4056 Basel, Switzerland Correspondence should be addressed to Michael Primig; Email: [email protected] Abstract Recent large-scale transcriptional profiling experiments of mammalian spermatogenesis using rodent model systems and different types of microarrays have yielded insight into the expression program of male germ cells. These studies revealed that an astonishingly large number of loci are differentially expressed during spermatogenesis. Among them are several hundred transcripts that appear to be specific for meiotic and post-meiotic germ cells. This group includes many genes that were pre- viously implicated in spermatogenesis and/or fertility and others that are as yet poorly characterized. Profiling experiments thus reveal candidates for regulation of spermatogenesis and fertility as well as targets for innovative contraceptives that act on gene products absent in somatic tissues. In this review, consolidated high density oligonucleotide microarray data from rodent total testis and purified germ cell samples are analyzed and their impact on our understanding of the transcriptional program governing male germ cell differentiation is discussed. Reproduction (2005) 129 1–7 Introduction 2002, Sadate-Ngatchou et al. 2003) and the absence of cAMP responsive-element modulator (Crem) and deleted During mammalian male
    [Show full text]
  • To Study Mutant P53 Gain of Function, Various Tumor-Derived P53 Mutants
    Differential effects of mutant TAp63γ on transactivation of p53 and/or p63 responsive genes and their effects on global gene expression. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science By Shama K Khokhar M.Sc., Bilaspur University, 2004 B.Sc., Bhopal University, 2002 2007 1 COPYRIGHT SHAMA K KHOKHAR 2007 2 WRIGHT STATE UNIVERSITY SCHOOL OF GRADUATE STUDIES Date of Defense: 12-03-07 I HEREBY RECOMMEND THAT THE THESIS PREPARED UNDER MY SUPERVISION BY SHAMA KHAN KHOKHAR ENTITLED Differential effects of mutant TAp63γ on transactivation of p53 and/or p63 responsive genes and their effects on global gene expression BE ACCEPTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF Master of Science Madhavi P. Kadakia, Ph.D. Thesis Director Daniel Organisciak , Ph.D. Department Chair Committee on Final Examination Madhavi P. Kadakia, Ph.D. Steven J. Berberich, Ph.D. Michael Leffak, Ph.D. Joseph F. Thomas, Jr., Ph.D. Dean, School of Graduate Studies 3 Abstract Khokhar, Shama K. M.S., Department of Biochemistry and Molecular Biology, Wright State University, 2007 Differential effect of TAp63γ mutants on transactivation of p53 and/or p63 responsive genes and their effects on global gene expression. p63, a member of the p53 gene family, known to play a role in development, has more recently also been implicated in cancer progression. Mice lacking p63 exhibit severe developmental defects such as limb truncations, abnormal skin, and absence of hair follicles, teeth, and mammary glands. Germline missense mutations of p63 have been shown to be responsible for several human developmental syndromes including SHFM, EEC and ADULT syndromes and are associated with anomalies in the development of organs of epithelial origin.
    [Show full text]
  • Epigenome-Wide Exploratory Study of Monozygotic Twins Suggests Differentially Methylated Regions to Associate with Hand Grip Strength
    Biogerontology (2019) 20:627–647 https://doi.org/10.1007/s10522-019-09818-1 (0123456789().,-volV)( 0123456789().,-volV) RESEARCH ARTICLE Epigenome-wide exploratory study of monozygotic twins suggests differentially methylated regions to associate with hand grip strength Mette Soerensen . Weilong Li . Birgit Debrabant . Marianne Nygaard . Jonas Mengel-From . Morten Frost . Kaare Christensen . Lene Christiansen . Qihua Tan Received: 15 April 2019 / Accepted: 24 June 2019 / Published online: 28 June 2019 Ó The Author(s) 2019 Abstract Hand grip strength is a measure of mus- significant CpG sites or pathways were found, how- cular strength and is used to study age-related loss of ever two of the suggestive top CpG sites were mapped physical capacity. In order to explore the biological to the COL6A1 and CACNA1B genes, known to be mechanisms that influence hand grip strength varia- related to muscular dysfunction. By investigating tion, an epigenome-wide association study (EWAS) of genomic regions using the comb-p algorithm, several hand grip strength in 672 middle-aged and elderly differentially methylated regions in regulatory monozygotic twins (age 55–90 years) was performed, domains were identified as significantly associated to using both individual and twin pair level analyses, the hand grip strength, and pathway analyses of these latter controlling the influence of genetic variation. regions revealed significant pathways related to the Moreover, as measurements of hand grip strength immune system, autoimmune disorders, including performed over 8 years were available in the elderly diabetes type 1 and viral myocarditis, as well as twins (age 73–90 at intake), a longitudinal EWAS was negative regulation of cell differentiation.
    [Show full text]
  • Aus Dem Institut Für Pharmakologie Der Medizinischen Hochschule Hannover
    Aus dem Institut für Pharmakologie der Medizinischen Hochschule Hannover Aufbau einer Datenbank für die Archivierung, Visualisierung und Auswertung von mRNA-Expressionsprofilen entzündungsrelevanter Gene auf der Basis eines standardisierten Oligonukleotid-DNA-Mikroarray-Systems Dissertation zur Erlangung des Doktorgrades der Humanbiologie der Medizinischen Hochschule Hannover vorgelegt von Axel Hans Robert Weber aus Kusel Hannover 2006 Angenommen vom Senat der Medizinischen Hochschule Hannover am 12. Juli 2006 Gedruckt mit Genehmigung der Medizinischen Hochschule Hannover Präsident: Prof. Dr. Dieter Bitter-Suermann Referent: Prof. Dr. Helmut Holtmann Korreferenten: Prof. Dr. Herbert Matthies Prof. Dr. M. Lienhard Schmitz Tag der mündlichen Prüfung 19. Juli 2006 Danksagung Die Durchführung und Niederschrift dieser Arbeit wäre nicht möglich gewesen ohne die Unterstützung und Förderung zahlreicher Personen. Mein besonderer Dank gilt meinem Doktorvater Prof. Dr. Michael Kracht für die hervorragende fachliche Betreuung dieser Arbeit sowie für zahlreiche Anregungen und Diskussionen. Dank gebührt auch Prof. Dr. Klaus Resch für die vielfältige Unterstützung innerhalb des Institutes für Pharmakologie. Herrn Dr. Oliver Dittrich-Breiholz, danke ich für die fundierte Einführung in das Thema DNA-Mikroarrays, die vielen fruchtbaren Diskussionen und die gute Zusammenarbeit beim Aufbau der Datenbank. Heike Schneider danke ich für die stete Hilfsbereitschaft und die unermüdliche Dateneingabe. Auch möchte ich mich bei Prof. Edgar Wingender und Dr. Alexander Kel von BIOBASE bedanken für die Kooperation und Überlassung der Auswertungsergebnisse. Nicht zuletzt gilt mein Dank natürlich auch allen Kooperationspartnern des Z02- Projektes für die Bereitstellung der Daten, die die Grundlage dieser Arbeit bilden. Die Arbeit wurde im Rahmen des DFG-Sonderforschungsbereiches SFB 566 Zytokin- Rezeptoren und Zytokin-abhängige Signalwege als therapeutische Zielstrukturen, im Teilprojekt Z02, „Identifizierung von differenziell regulierten Genen mittels DNA Microarrays” erstellt.
    [Show full text]
  • Pancancer Progression Human Vjune2017
    Gene Symbol Accession Alias/Prev Symbol Official Full Name AAMP NM_001087.3 - angio-associated, migratory cell protein ABI3BP NM_015429.3 NESHBP|TARSH ABI family, member 3 (NESH) binding protein ACHE NM_000665.3 ACEE|ARACHE|N-ACHE|YT acetylcholinesterase ACTG2 NM_001615.3 ACT|ACTA3|ACTE|ACTL3|ACTSG actin, gamma 2, smooth muscle, enteric ACVR1 NM_001105.2 ACTRI|ACVR1A|ACVRLK2|ALK2|FOP|SKR1|TSRI activin A receptor, type I ACVR1C NM_145259.2 ACVRLK7|ALK7 activin A receptor, type IC ACVRL1 NM_000020.1 ACVRLK1|ALK-1|ALK1|HHT|HHT2|ORW2|SKR3|TSR-I activin A receptor type II-like 1 ADAM15 NM_207195.1 MDC15 ADAM metallopeptidase domain 15 ADAM17 NM_003183.4 ADAM18|CD156B|CSVP|NISBD|TACE ADAM metallopeptidase domain 17 ADAM28 NM_014265.4 ADAM 28|ADAM23|MDC-L|MDC-Lm|MDC-Ls|MDCL|eMDC II|eMDCII ADAM metallopeptidase domain 28 ADAM8 NM_001109.4 CD156|MS2 ADAM metallopeptidase domain 8 ADAM9 NM_001005845.1 CORD9|MCMP|MDC9|Mltng ADAM metallopeptidase domain 9 ADAMTS1 NM_006988.3 C3-C5|METH1 ADAM metallopeptidase with thrombospondin type 1 motif, 1 ADAMTS12 NM_030955.2 PRO4389 ADAM metallopeptidase with thrombospondin type 1 motif, 12 ADAMTS8 NM_007037.4 ADAM-TS8|METH2 ADAM metallopeptidase with thrombospondin type 1 motif, 8 ADAP1 NM_006869.2 CENTA1|GCS1L|p42IP4 ArfGAP with dual PH domains 1 ADD1 NM_001119.4 ADDA adducin 1 (alpha) ADM2 NM_001253845.1 AM2|dJ579N16.4 adrenomedullin 2 ADRA2B NM_000682.4 ADRA2L1|ADRA2RL1|ADRARL1|ALPHA2BAR|alpha-2BAR adrenoceptor alpha 2B AEBP1 NM_001129.3 ACLP AE binding protein 1 AGGF1 NM_018046.3 GPATC7|GPATCH7|HSU84971|HUS84971|VG5Q
    [Show full text]
  • Frequent Loss of Heterozygosity Targeting the Inactive X Chromosome in Melanoma
    6476 Vol. 9, 6476–6482, December 15, 2003 Clinical Cancer Research Frequent Loss of Heterozygosity Targeting the Inactive X Chromosome in Melanoma James O. Indsto,1 Najah T. Nassif,2 INTRODUCTION Richard F. Kefford,1 and Graham J. Mann1 Chromosomal deletions and amplification events are fre- 1Westmead Institute for Cancer Research, University of Sydney at quent in advanced neoplasms and provide evidence for the Westmead Millennium Institute, Westmead, New South Wales, existence and location of putative tumor suppressor genes Australia, and 2Department of Cell and Molecular Biology, University (TSGs) and oncogenes. In melanoma, 9p and 10q deletions are of Technology, Sydney, New South Wales, Australia most frequent, and losses on 6q, 11q, 1p, 15p, 17q, and 18q are also frequently found (1, 2). However, no studies have focused on the X chromosome. In the human female, random inactiva- ABSTRACT tion of one copy of an X chromosome by hypermethylation is an After previous preliminary observations of paradoxical early event in embryogenesis, resulting in most tissues being a deletion events affecting the inactive X chromosome in mel- mosaic in terms of X inactivation status. Neoplasms, being anoma, we have surveyed the X chromosome for deletions clonal expansions of single precursor cells, usually share a using 23 polymorphic microsatellite markers in 28 inform- common X inactivation status. This can be conveniently assayed ative (female XX) metastatic melanomas. Ten tumors (36%) using the methylation-sensitive restriction enzyme HpaII, which showed at least one loss of heterozygosity (LOH) event, and has a recognition site within the highly polymorphic exon 1 in two cases an entire chromosome showed LOH at all CAG repeat (ARTR) in the androgen receptor (AR) gene.
    [Show full text]