DOCSLIB.ORG

Mouse Models for Identifying Genes Modulating Fertility Parameters Paul Laissue, D

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mouse Models for Identifying Genes Modulating Fertility Parameters Paul Laissue, D Mouse models for identifying genes modulating fertility parameters Paul Laissue, D. l’Hote, Catherine Serres, Daniel Vaiman To cite this version: Paul Laissue, D. l’Hote, Catherine Serres, Daniel Vaiman. Mouse models for identifying genes modu- lating fertility parameters. animal, Published by Elsevier (since 2021) / Cambridge University Press (until 2020), 2009, 3 (1), pp.55-71. 10.1017/S1751731108003315. hal-02661605 HAL Id: hal-02661605 https://hal.inrae.fr/hal-02661605 Submitted on 30 May 2020 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. Animal (2009), 3:1, pp 55–71 & The Animal Consortium 2008 animal doi:10.1017/S1751731108003315 Mouse models for identifying genes modulating fertility parameters - P. Laissue1,2,3*, D. L’Hoˆ te1,2,3*, C. Serres1,2,3 and D. Vaiman1,2,3,4 1INSERM U567, Team21 ‘Genomics and Epigenetics of Placental Diseases’, Genetics and Development Department, Institute Cochin, 24 rue du Faubourg St-Jacques, 75014 Paris, France; 2CNRS UMR8104, Institute Cochin, 24 rue du Faubourg St-Jacques, 75014 Paris, France; 3Faculte´ de Me´decine Cochin-Port-Royal, Universite´ Paris Descartes, 24 rue du Faubourg St-Jacques, 75014 Paris, France; 4INRA Animal Genetics Department, France (Received 15 November 2007; Accepted 20 June 2008; First published online 8 October 2008) Fertility can be defined as the natural capability of giving life. It is an important factor both for human medicine, where ,10% of the couples call for the services of assisted reproductive technologies, and for species of economic interest. In particular, in dairy cows, the recent years have seen a kind of competition between milk production and fertility, and genes improving fertility are now considered as parameters to be selected for. The study of fertility pathways is nevertheless made difficult by the strong impact of environmental factors on this parameter, as well as by the number of genes potentially involved (as shown by systematic transcriptome analysis studies in the recent years). One additional level of complexity is given by the fact that factors modulating fertility will probably be sex specific. The usage of mouse models has been one of the solutions exploited for tackling with these difficulties. Here, we review three different approaches using mice for identifying genes modulating fertility in mammals: gene invalidation, positional cloning and in vitro mutagenesis. These three approaches exploit specific characteristics of the mouse, such as the possibility of controlling precisely the environment, an excellent genetic characterization and the existence of genomic and molecular tools equalled only in humans. Many indications suggest that at least some of the results obtained in mice could be easily transposed to the species of interest. Keywords: fertility, mice, gametogenesis, cattle, humans Introduction obvious target for selection to play with. Such selection pressure is presumably an important reason why, despite the Inherent complexity of the sexual reproduction and its complexity of the reproductive system, things seem to work implications in evolution pretty well. Mammalian reproduction encompasses several highly con- voluted phases: gamete production, gamete encounter and fusion, early development, implantation and post-implanta- Cost/benefit of sexual reproduction: the example tion developmental stages. These intertwined phases involve of high-producer dairy cows the modification and put on gear thousands of genes. This From an evolutionary point of view, two contradictory fact, which is not a posteriori surprising, was nevertheless trends seem to be at work in mammalian reproduction: considerably underestimated before the setting up of pan- an irreducible complexity for fabricating male and female genomic approaches of gene expression analysis carried out gametes in order to allow the fecundation and the vital from the early events of sex determination (Nef et al., 2005; necessity of the system for the mere survival of the species. Beverdam and Koopman, 2006; Cederroth et al., 2007) to In this context, another parameter can be taken into implantation (Giudice, 2003; Talbi et al., 2006). Any improper account concerning the instance of energy and resource regulation in either phase of the highly complex network of allotment. Indeed sexual reproduction is a costly method of genes involved may lead to infertility. The selection pressure survival, especially in female mammals, where the normal applied to reproduction is huge and if fitness is defined as follow-up of fecundation consists of long-lasting hosting of the capability of producing living offspring, then fertility is an one or several greedy foetuses. This essential biological and evolutionary condition is made even more severe by the fact * PL and DL contributed equally to the redaction of this paper. that parturition in most mammalian species is followed by - E-mail: [email protected] thecareoftheoffspringduringweeks,monthsorevenyears. 55 Laissue, L’Hoˆ te, Serres and Vaiman All these drawbacks are therefore to be counter-balanced by an increased fitness. Recently, the true cost of prolificacy has been illustrated by dairy cows producing ever higher amounts of milk (from 2500 kg in 1945 to almost 9000 kg a year today). This evolution has been particularly rapid in the last 20 years and it is estimated at 3000 kg from 1986 to 2006. In parallel and sometimes controversially, infertility has started to be a significant problem in cattle farming, evocating a potential antagonistic relation opposing fertility and high production, albeit up to now such a negative relationship has not been strictly demonstrated (Lopez-Gatius et al., 2006; Garcia-Ispierto et al., 2007). Elucidating the genetic control of reproductive functions is a Figure 1 One of the main interests of using mice as animal models is the difficult challenge fact that they are available as strains, meaning that their chromosome Heritability of reproductive parameters. The heritability of content is homozygous at every locus. Intra-strain crosses are largely reproduction parameters remains relatively elusive but most comparable to the mating of cloned animals, which, genetically speaking, reports suggest that it is either very low (0.05 or less) or should yield only identical animals, but the rare events of point mutations. By contrast, outbred species such as humans or species, which have weak (less than 0.20) (Bergmann and Hohenboken, 1992; been heavily selected for agricultural traits, have a strong level of Jamrozik et al., 2005; Bormann et al., 2006). Two likely heterozygosity. In the figure, homozygous regions are shown by brackets. reasons for this may be either a very strong influence of For traits displaying a low heritability, either because they are genetically external factors (light, temperature, hormonal and dietary ill-defined or because environmental factors play a major role, crosses between mice species are very useful, since environmental conditions can status) on the phenotype, which makes it difficult to isolate be very precisely controlled, and because the genetic diversity is obtained the genetic component of the observed variance, or a very by crossing existing strains, or by analyzing recombinant congenic strains. high underlying genetic complexity. General statements on human infertility treatments.In mouse, characterized by its short generation time, high humans, infertility affects up to 10% of the couples in prolificacy and small size (Figure 1). The debate of trans- industrialized countries (Feng, 2003) and the complexity of porting data from mice to humans or other species is the underlying biological disorders remains largely controversial and never-ending. However, it should be unknown at the molecular level. The responses brought to recognized that many advances on mammalian physiology the patients involve technological approaches based upon and genetics originate from mouse studies. two essential techniques: in vitro fecundation (IVF) and Reproduction has not escaped this reality and several intra-cytoplasmic sperm injection (ICSI). These approaches research groups around the world use laboratory mice to are meant to alleviate or escape the problems encountered evaluate fertility parameters. One of the important char- during gamete production, gamete encounter and fusion, acteristics of laboratory mice is that they exist as strains, early development and implantation. Such therapeutics, a collection of genetically identical animals. These strains generally based upon gamete and/or embryo manipula- show complete homozygosity at all genomic loci, of course tions, bring immediate solution to patient’s infertility but higher than in clones, which can be heterozygous at moves the possible genetical basis of the fertility problem numerous loci. This situation lessens considerably the to the next generation (Cram et al., 2000; Meschede et al., potential influences of individual genetic heterogeneity 2000). compared with other species. Different types of mouse models have been constructed corresponding
Load more

Recommended publications
  • Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-Like Mouse Models: Tracking the Role of the Hairless Gene
    University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 5-2006 Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene Yutao Liu University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Life Sciences Commons Recommended Citation Liu, Yutao, "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino- like Mouse Models: Tracking the Role of the Hairless Gene. " PhD diss., University of Tennessee, 2006. https://trace.tennessee.edu/utk_graddiss/1824 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Yutao Liu entitled "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Life Sciences. Brynn H. Voy, Major Professor We have read this dissertation and recommend its acceptance: Naima Moustaid-Moussa, Yisong Wang, Rogert Hettich Accepted for the Council: Carolyn R.
    [Show full text]
  • RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases
    G C A T T A C G G C A T genes Review RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases Amber Willbanks, Shaun Wood and Jason X. Cheng * Department of Pathology, Hematopathology Section, University of Chicago, Chicago, IL 60637, USA; [email protected] (A.W.); [email protected] (S.W.) * Correspondence: [email protected] Abstract: Chromatin structure plays an essential role in eukaryotic gene expression and cell identity. Traditionally, DNA and histone modifications have been the focus of chromatin regulation; however, recent molecular and imaging studies have revealed an intimate connection between RNA epigenetics and chromatin structure. Accumulating evidence suggests that RNA serves as the interplay between chromatin and the transcription and splicing machineries within the cell. Additionally, epigenetic modifications of nascent RNAs fine-tune these interactions to regulate gene expression at the co- and post-transcriptional levels in normal cell development and human diseases. This review will provide an overview of recent advances in the emerging field of RNA epigenetics, specifically the role of RNA modifications and RNA modifying proteins in chromatin remodeling, transcription activation and RNA processing, as well as translational implications in human diseases. Keywords: 5’ cap (5’ cap); 7-methylguanosine (m7G); R-loops; N6-methyladenosine (m6A); RNA editing; A-to-I; C-to-U; 2’-O-methylation (Nm); 5-methylcytosine (m5C); NOL1/NOP2/sun domain Citation: Willbanks, A.; Wood, S.; (NSUN); MYC Cheng, J.X. RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases. Genes 2021, 12, 627.
    [Show full text]
  • 1 Metabolic Dysfunction Is Restricted to the Sciatic Nerve in Experimental
    Page 1 of 255 Diabetes Metabolic dysfunction is restricted to the sciatic nerve in experimental diabetic neuropathy Oliver J. Freeman1,2, Richard D. Unwin2,3, Andrew W. Dowsey2,3, Paul Begley2,3, Sumia Ali1, Katherine A. Hollywood2,3, Nitin Rustogi2,3, Rasmus S. Petersen1, Warwick B. Dunn2,3†, Garth J.S. Cooper2,3,4,5* & Natalie J. Gardiner1* 1 Faculty of Life Sciences, University of Manchester, UK 2 Centre for Advanced Discovery and Experimental Therapeutics (CADET), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK 3 Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK 4 School of Biological Sciences, University of Auckland, New Zealand 5 Department of Pharmacology, Medical Sciences Division, University of Oxford, UK † Present address: School of Biosciences, University of Birmingham, UK *Joint corresponding authors: Natalie J. Gardiner and Garth J.S. Cooper Email: [email protected]; [email protected] Address: University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, United Kingdom Telephone: +44 161 275 5768; +44 161 701 0240 Word count: 4,490 Number of tables: 1, Number of figures: 6 Running title: Metabolic dysfunction in diabetic neuropathy 1 Diabetes Publish Ahead of Print, published online October 15, 2015 Diabetes Page 2 of 255 Abstract High glucose levels in the peripheral nervous system (PNS) have been implicated in the pathogenesis of diabetic neuropathy (DN). However our understanding of the molecular mechanisms which cause the marked distal pathology is incomplete. Here we performed a comprehensive, system-wide analysis of the PNS of a rodent model of DN.
    [Show full text]
  • Liver Glucose Metabolism in Humans
    Biosci. Rep. (2016) / 36 / art:e00416 / doi 10.1042/BSR20160385 Liver glucose metabolism in humans Mar´ıa M. Adeva-Andany*1, Noemi Perez-Felpete*,´ Carlos Fernandez-Fern´ andez*,´ Cristobal´ Donapetry-Garc´ıa* and Cristina Pazos-Garc´ıa* *Nephrology Division, Hospital General Juan Cardona, c/ Pardo Bazan´ s/n, 15406 Ferrol, Spain Synopsis Information about normal hepatic glucose metabolism may help to understand pathogenic mechanisms underlying obesity and diabetes mellitus. In addition, liver glucose metabolism is involved in glycosylation reactions and con- nected with fatty acid metabolism. The liver receives dietary carbohydrates directly from the intestine via the portal vein. Glucokinase phosphorylates glucose to glucose 6-phosphate inside the hepatocyte, ensuring that an adequate flow of glucose enters the cell to be metabolized. Glucose 6-phosphate may proceed to several metabolic path- ways. During the post-prandial period, most glucose 6-phosphate is used to synthesize glycogen via the formation of glucose 1-phosphate and UDP–glucose. Minor amounts of UDP–glucose are used to form UDP–glucuronate and UDP– galactose, which are donors of monosaccharide units used in glycosylation. A second pathway of glucose 6-phosphate metabolism is the formation of fructose 6-phosphate, which may either start the hexosamine pathway to produce UDP-N-acetylglucosamine or follow the glycolytic pathway to generate pyruvate and then acetyl-CoA. Acetyl-CoA may enter the tricarboxylic acid (TCA) cycle to be oxidized or may be exported to the cytosol to synthesize fatty acids, when excess glucose is present within the hepatocyte. Finally, glucose 6-phosphate may produce NADPH and ribose 5-phosphate through the pentose phosphate pathway.
    [Show full text]
  • Growth and Gene Expression Profile Analyses of Endometrial Cancer Cells Expressing Exogenous PTEN
    [CANCER RESEARCH 61, 3741–3749, May 1, 2001] Growth and Gene Expression Profile Analyses of Endometrial Cancer Cells Expressing Exogenous PTEN Mieko Matsushima-Nishiu, Motoko Unoki, Kenji Ono, Tatsuhiko Tsunoda, Takeo Minaguchi, Hiroyuki Kuramoto, Masato Nishida, Toyomi Satoh, Toshihiro Tanaka, and Yusuke Nakamura1 Laboratories of Molecular Medicine [M. M-N., M. U., K. O., T. M., T. Ta., Y. N.] and Genome Database [T. Ts.], Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Department of Obstetrics and Gynecology, School of Medicine, Kitasato University, Sagamihara 228-8555, Japan [H. K.]; Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba 305-8576, Japan [M. N.]; and Department of Obstetrics and Gynecology, Ibaraki Seinan Central Hospital, Tsukuba 306-0433, Japan [T. S.] ABSTRACT Akt/protein kinase B, cell survival, and cell proliferation (8). Over- expression of PTEN can decrease cell proliferation and tumorigenicity The PTEN tumor suppressor gene encodes a multifunctional phospha- (9, 10), an observation attributed to the ability of PTEN to induce cell tase that plays an important role in inhibiting the phosphatidylinositol-3- cycle arrest and apoptosis (11, 12). kinase pathway and downstream functions that include activation of Akt/protein kinase B, cell survival, and cell proliferation. Enforced ex- Thus, lack of PTEN expression may affect a complex set of pression of PTEN in various cancer cell lines decreases cell proliferation transcriptional targets. However, no systematic assessment of PTEN- through arrest of the cell cycle, accompanied in some cases by induction regulated targets in cancer cells has been reported to date.
    [Show full text]
  • Role and Regulation of the P53-Homolog P73 in the Transformation of Normal Human Fibroblasts
    Role and regulation of the p53-homolog p73 in the transformation of normal human fibroblasts Dissertation zur Erlangung des naturwissenschaftlichen Doktorgrades der Bayerischen Julius-Maximilians-Universität Würzburg vorgelegt von Lars Hofmann aus Aschaffenburg Würzburg 2007 Eingereicht am Mitglieder der Promotionskommission: Vorsitzender: Prof. Dr. Dr. Martin J. Müller Gutachter: Prof. Dr. Michael P. Schön Gutachter : Prof. Dr. Georg Krohne Tag des Promotionskolloquiums: Doktorurkunde ausgehändigt am Erklärung Hiermit erkläre ich, dass ich die vorliegende Arbeit selbständig angefertigt und keine anderen als die angegebenen Hilfsmittel und Quellen verwendet habe. Diese Arbeit wurde weder in gleicher noch in ähnlicher Form in einem anderen Prüfungsverfahren vorgelegt. Ich habe früher, außer den mit dem Zulassungsgesuch urkundlichen Graden, keine weiteren akademischen Grade erworben und zu erwerben gesucht. Würzburg, Lars Hofmann Content SUMMARY ................................................................................................................ IV ZUSAMMENFASSUNG ............................................................................................. V 1. INTRODUCTION ................................................................................................. 1 1.1. Molecular basics of cancer .......................................................................................... 1 1.2. Early research on tumorigenesis ................................................................................. 3 1.3. Developing
    [Show full text]
  • The Role of the NFAT Signalling Pathway in Diffuse Large B-Cell Lymphoma
    The role of the NFAT signalling pathway in Diffuse Large B-cell Lymphoma Holly White Doctor of Philosophy Thesis September 2015 Supervisors: Dr Chris Bacon, Professor Neil Perkins & Dr Vikki Rand Northern Institute for Cancer Research Word count: 66,024 1 Abstract Diffuse Large B-Cell Lymphomas (DLBCL) are common, aggressive malignancies of mature B-lymphocytes that represent ~40% of lymphomas. Despite the widespread use of combined immunochemotherapy, approximately 50% of patients with DLBCL die from their disease. The two main DLBCL subgroups resemble activated B cells (ABC) or germinal centre B cells (GCB), where patients with ABC-DLBCL have significantly worse outcome. There is urgent need for novel therapeutic strategies in the treatment of DLBCL, which requires a better understanding of the molecular pathways upon which tumours depend. Accumulating evidence suggests that the signalling networks promoting and sustaining DLBCL derive from dysregulation of the normal pathways controlling B-lymphocyte activation and differentiation. There is increasing evidence indicating important roles for the NFAT family of transcription factors in DLBCL. Constitutively-active nuclear NFAT2 has been demonstrated in approximately 40% of primary DLBCL samples and NFAT has been shown to regulate a small number of genes associated with DLBCL growth/survival. This project investigated the role of NFAT in DLBCL. Nuclear localisation and activation of NFAT family members were characterised in a panel of DLBCL cell lines and chemical inhibition of calcineurin/NFAT, using Cyclosporin A (CsA), indicated dependency on the calcineurin/NFAT pathway for survival. Gene expression microarray analysis performed in DLBCL cell lines treated with CsA revealed potential NFAT target genes involved in the tumour microenvironment and anergy.
    [Show full text]
  • Identification of Molecular Targets in Head and Neck Squamous Cell Carcinomas Based on Genome-Wide Gene Expression Profiling
    1489-1497 7/11/07 18:41 Page 1489 ONCOLOGY REPORTS 18: 1489-1497, 2007 Identification of molecular targets in head and neck squamous cell carcinomas based on genome-wide gene expression profiling SATOYA SHIMIZU1,2, NAOHIKO SEKI2, TAKASHI SUGIMOTO2, SHIGETOSHI HORIGUCHI1, HIDEKI TANZAWA3, TOYOYUKI HANAZAWA1 and YOSHITAKA OKAMOTO1 Departments of 1Otorhinolaryngology, 2Functional Genomics and 3Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan Received May 21, 2007; Accepted June 28, 2007 Abstract. DNA amplifications activate oncogenes and are patients and metastases develop in 15-25% of patients (1). hallmarks of nearly all advanced cancers including head and Many factors, such as TNM stage, pathological grade and neck squamous cell carcinoma (HNSCC). Some oncogenes tumor site, influence the prognosis of HNSCC but are not show both DNA copy number gain and mRNA overexpression. sufficient to predict outcome. In addition, treatment often Chromosomal comparative genomic hybridization and oligo- results in impairment of functions such as speech and nucleotide microarrays were used to examine 8 HNSCC cell swallowing, cosmetic disfiguration and mental pain. These lines and a plot of gene expression levels relative to their inflictions significantly erode quality of life. To overcome this position on the chromosome was produced. Three highly situation, there is a need to find novel biomarkers that classify up-regulated genes, NT5C3, ANLN and INHBA, were patients into prognostic groups, to aid identification of high- identified on chromosome 7p14. These genes were subjected risk patients who may benefit from different treatments. to quantitative real-time RT-PCR on cDNA and genomic Comparative genomic hybridization (CGH) has facilitated DNA derived from 8 HNSCC cell lines.
    [Show full text]
  • PGM3 Rabbit Polyclonal Antibody – TA345110 | Origene
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA345110 PGM3 Rabbit Polyclonal Antibody Product data: Product Type: Primary Antibodies Applications: WB Recommended Dilution: WB Reactivity: Human Host: Rabbit Isotype: IgG Clonality: Polyclonal Immunogen: The immunogen for anti-PGM3 antibody: synthetic peptide directed towards the middle region of human PGM3. Synthetic peptide located within the following region: GVVQTAYANGSSTRYLEEVMKVPVYCTKTGVKHLHHKAQEFDIGVYFEAN Formulation: Liquid. Purified antibody supplied in 1x PBS buffer with 0.09% (w/v) sodium azide and 2% sucrose. Note that this product is shipped as lyophilized powder to China customers. Purification: Affinity Purified Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Predicted Protein Size: 60 kDa Gene Name: phosphoglucomutase 3 Database Link: NP_056414 Entrez Gene 5238 Human O95394 Background: This gene encodes a member of the phosphohexose mutase family. The encoded protein mediates both glycogen formation and utilization by catalyzing the interconversion of glucose-1-phosphate and glucose-6-phosphate. A non-synonymous single nucleotide polymorphism in this gene may play a role in resistance to diabetic nephropathy and neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq,
    [Show full text]
  • 2014-Platform-Abstracts.Pdf
    American Society of Human Genetics 64th Annual Meeting October 18–22, 2014 San Diego, CA PLATFORM ABSTRACTS Abstract Abstract Numbers Numbers Saturday 41 Statistical Methods for Population 5:30pm–6:50pm: Session 2: Plenary Abstracts Based Studies Room 20A #198–#205 Featured Presentation I (4 abstracts) Hall B1 #1–#4 42 Genome Variation and its Impact on Autism and Brain Development Room 20BC #206–#213 Sunday 43 ELSI Issues in Genetics Room 20D #214–#221 1:30pm–3:30pm: Concurrent Platform Session A (12–21): 44 Prenatal, Perinatal, and Reproductive 12 Patterns and Determinants of Genetic Genetics Room 28 #222–#229 Variation: Recombination, Mutation, 45 Advances in Defining the Molecular and Selection Hall B1 Mechanisms of Mendelian Disorders Room 29 #230–#237 #5-#12 13 Genomic Studies of Autism Room 6AB #13–#20 46 Epigenomics of Normal Populations 14 Statistical Methods for Pedigree- and Disease States Room 30 #238–#245 Based Studies Room 6CF #21–#28 15 Prostate Cancer: Expression Tuesday Informing Risk Room 6DE #29–#36 8:00pm–8:25am: 16 Variant Calling: What Makes the 47 Plenary Abstracts Featured Difference? Room 20A #37–#44 Presentation III Hall BI #246 17 New Genes, Incidental Findings and 10:30am–12:30pm:Concurrent Platform Session D (49 – 58): Unexpected Observations Revealed 49 Detailing the Parts List Using by Exome Sequencing Room 20BC #45–#52 Genomic Studies Hall B1 #247–#254 18 Type 2 Diabetes Genetics Room 20D #53–#60 50 Statistical Methods for Multigene, 19 Genomic Methods in Clinical Practice Room 28 #61–#68 Gene Interaction
    [Show full text]
  • Supplementary Tables S1-S3
    Supplementary Table S1: Real time RT-PCR primers COX-2 Forward 5’- CCACTTCAAGGGAGTCTGGA -3’ Reverse 5’- AAGGGCCCTGGTGTAGTAGG -3’ Wnt5a Forward 5’- TGAATAACCCTGTTCAGATGTCA -3’ Reverse 5’- TGTACTGCATGTGGTCCTGA -3’ Spp1 Forward 5'- GACCCATCTCAGAAGCAGAA -3' Reverse 5'- TTCGTCAGATTCATCCGAGT -3' CUGBP2 Forward 5’- ATGCAACAGCTCAACACTGC -3’ Reverse 5’- CAGCGTTGCCAGATTCTGTA -3’ Supplementary Table S2: Genes synergistically regulated by oncogenic Ras and TGF-β AU-rich probe_id Gene Name Gene Symbol element Fold change RasV12 + TGF-β RasV12 TGF-β 1368519_at serine (or cysteine) peptidase inhibitor, clade E, member 1 Serpine1 ARE 42.22 5.53 75.28 1373000_at sushi-repeat-containing protein, X-linked 2 (predicted) Srpx2 19.24 25.59 73.63 1383486_at Transcribed locus --- ARE 5.93 27.94 52.85 1367581_a_at secreted phosphoprotein 1 Spp1 2.46 19.28 49.76 1368359_a_at VGF nerve growth factor inducible Vgf 3.11 4.61 48.10 1392618_at Transcribed locus --- ARE 3.48 24.30 45.76 1398302_at prolactin-like protein F Prlpf ARE 1.39 3.29 45.23 1392264_s_at serine (or cysteine) peptidase inhibitor, clade E, member 1 Serpine1 ARE 24.92 3.67 40.09 1391022_at laminin, beta 3 Lamb3 2.13 3.31 38.15 1384605_at Transcribed locus --- 2.94 14.57 37.91 1367973_at chemokine (C-C motif) ligand 2 Ccl2 ARE 5.47 17.28 37.90 1369249_at progressive ankylosis homolog (mouse) Ank ARE 3.12 8.33 33.58 1398479_at ryanodine receptor 3 Ryr3 ARE 1.42 9.28 29.65 1371194_at tumor necrosis factor alpha induced protein 6 Tnfaip6 ARE 2.95 7.90 29.24 1386344_at Progressive ankylosis homolog (mouse)
    [Show full text]
  • Short- and Long-Term Impact of Hyperoxia on the Blood and Retinal Cells’ Transcriptome in a Mouse Model of Oxygen- Induced Retinopathy
    www.nature.com/pr BASIC SCIENCE ARTICLE OPEN Short- and long-term impact of hyperoxia on the blood and retinal cells’ transcriptome in a mouse model of oxygen- induced retinopathy Magdalena Zasada1, Anna Madetko-Talowska2, Cecilie Revhaug3,4, Anne Gro W. Rognlien3,4, Lars O. Baumbusch3,Teofila Książek2, Katarzyna Szewczyk2, Agnieszka Grabowska2, Miroslaw Bik-Multanowski2, Jacek Józef Pietrzyk1, Przemko Kwinta1 and Ola Didrik Saugstad3,4 BACKGROUND: We aimed to identify global blood and retinal gene expression patterns in murine oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity, which may allow better understanding of the pathogenesis of this severe ocular prematurity complication and identification of potential blood biomarkers. METHODS: A total of 120 C57BL/6J mice were randomly divided into an OIR group, in which 7-day-old pups were maintained in 75% oxygen for 5 days, or a control group. RNA was extracted from the whole-blood mononuclear cells and retinal cells on days 12, 17, and 28. Gene expression in the RNA samples was evaluated with mouse gene expression microarrays. RESULTS: There were 38, 1370 and 111 genes, the expression of which differed between the OIR and control retinas on days 12, 17, and 28, respectively. Gene expression in the blood mononuclear cells was significantly altered only on day 17. Deptor and Nol4 genes showed reduced expression both in the blood and retinal cells on day 17. 1234567890();,: CONCLUSION: There are sustained marked changes in the global pattern of gene expression in the OIR mice retinas. An altered expression of Deptor and Nol4 genes in the blood mononuclear cells requires further investigation as they may indicate retinal neovascularization.
    [Show full text]