DOCSLIB.ORG

Differential Epigenomic and Transcriptomic Responses in Subcutaneous Adipose Tissue Between Low and High Responders to Caloric Restriction1–3

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Differential Epigenomic and Transcriptomic Responses in Subcutaneous Adipose Tissue Between Low and High Responders to Caloric Restriction1–3 Differential epigenomic and transcriptomic responses in subcutaneous adipose tissue between low and high responders to caloric restriction1–3 Luigi Bouchard, Re´mi Rabasa-Lhoret, May Faraj, Marie-E`ve Lavoie, Jonathan Mill, Louis Pe´russe, and Marie-Claude Vohl ABSTRACT weight loss responses to caloric restriction show considerable Background: Caloric restriction is recommended for the treatment interindividual variability (7). Studies of genetically identical of obesity, but it is generally characterized by large interindividual monozygotic twins have been particularly useful in disentangling variability in responses. The factors affecting the magnitude of the role of environmental and heritable factors in determining the weight loss remain poorly understood. Epigenetic factors (ie, heri- degree of weight loss. It has been shown that within-pair changes table but reversible changes to genomic function that regulate gene in body fat variability after a caloric deficit is significantly lower expression independently of DNA sequence) may explain some of than between-pair variability, which suggests that genetic factors the interindividual variability seen in weight-loss responses. have an important influence on an individual’s response to caloric Objective: The objective was to determine whether epigenetics and deficit (8, 9). However, the concordance between twin pairs was gene expression changes may play a role in weight-loss responsiveness. not complete, which suggests that environmental factors or other Design: Overweight/obese postmenopausal women were recruited DNA sequence–independent mechanisms may be involved. for a standard 6-mo caloric restriction intervention. Abdominal sub- It has been suggested that monozygotic twin discordance for cutaneous adipose tissue biopsy samples were collected before (n = complex traits such as body weight could be accounted for by 14) and after (n = 14) intervention, and the epigenomic and tran- epigenetic factors (10, 11). Epigenetics refers to the heritable, but scriptomic profiles of the high and low responders to dieting, on the reversible, regulation of various genomic functions, including basis of changes in percentage body fat, were compared by using gene transcription, that are mediated principally through changes microarray analysis. in DNA methylation and chromatin structure (12). The epigenetic Results: Significant DNA methylation differences at 35 loci were regulation of cellular functions is a normal and essential process found between the high and low responders before dieting, with 3 in cell development and differentiation, and epigenetic factors are regions showing differential methylation after intervention. Some of subjected to reprogramming in response to both stochastic and these regions contained genes known to be involved in weight con- environmental stimuli (12). Such changes can be mitotically trol and insulin secretion, whereas others were localized in known imprinted genomic regions. Differences in gene expression profiles were observed only after dieting, with 644 genes being differen- 1 From the Nutraceuticals and Functional Foods Institute (LB, LP, and M- tially expressed between the 2 groups. These included genes likely CV), the Department of Preventive Medicine (LP), and the Department of to be involved in metabolic pathways related to angiogenesis and Food Science and Nutrition (M-CV), Universite´ Laval, Laval, Canada; the cerebellar long-term depression. Department of Medicine, Universite´ de Montre´al, Chicoutimi Hospital, Sa- Conclusions: These data show that both DNA methylation and gene guenay, Canada (LB); the Department of Nutrition (RR-L, MF, and M-EL), expression are responsive to caloric restriction and provide new the Montreal Diabetes Research Centre (RR-L and MF), Universite´ de Mon- tre´al, Montreal, Canada; and the Institute of Psychiatry, SGDP Research insights about the molecular pathways involved in body weight loss Centre, King’s College London, London, United Kingdom (JM). as well as methylation regulation during adulthood. Am J Clin 2 Supported by the Canadian Institute of Health Research through the Nutr 2010;91:309–20. MONET project (Montreal-Ottawa New Emerging Team; OHN-63279 and MOP62976) and the Quebec New Emerging Team (OHN 63276). LB was INTRODUCTION funded by the Laval University Merck Frosst/Canadian Institute of Health Research Chair in Obesity and the Heart and Stroke Foundation of Canada/ In 2005, 1.1 billion adults and 10% of children were over- Sanofi-Aventis research fellowship awards. RRL was supported by the Fonds weight or obese worldwide (1). Obesity is defined as an excessive de la Recherche en Sante´ du Que´bec and held the chair for clinical research accumulation of fat resulting from a long-term imbalance be- J-A de Se`ve at IRCM (Montreal Institute for Clinical Research). MF was the tween energy intake and expenditure (2). It has a dramatic effect recipient of the Canadian Institute of Health Research New Investigator on an individual’s health, with musculoskeletal, pulmonary, and Award. M-EL was supported by a scholarship from the Fonds de la Re- ´ ´ psychosocial-related problems, and is associated with an in- cherche en Sante du Quebec. 3 Address correspondence to M-C Vohl, Lipid Research Center, 2705 creased risk of morbidity and mortality attributable to cardio- Laurier Boulevard, (TR93), Que´bec City, PQ, Canada G1V 4G2. E-mail: vascular diseases, diabetes, and certain forms of cancer (1, 3). [email protected]. Interestingly, only a moderate loss of initial body weight Received May 18, 2009. Accepted for publication November 2, 2009. provides significant metabolic improvements (4–6). However, First published online November 25, 2009; doi: 10.3945/ajcn.2009.28085. Am J Clin Nutr 2010;91:309–20. Printed in USA. Ó 2010 American Society for Nutrition 309 310 BOUCHARD ET AL stable and enduring, producing long-term changes to gene ex- adipose tissue biopsy collections were preceded by a 4-wk pression, but can also be short-lived and rapidly reversed (13). weight-stability period (within 62 kg), verified on a weekly Indeed, such dynamic epigenetic changes have the potential to basis at our research unit. Also, the subjects were instructed not offer a mechanism by which cellular metabolism can be rapidly to exercise and to eat a high-carbohydrate diet for the 3 d before regulated independently of long-term, irreversible evolutionary the biopsy procedure. Fasting baseline and postintervention mutagenesis. Cytosine methylation (Cmet), occurring at position subcutaneous adipose tissue biopsy samples were obtained from 5 of the cytosine pyrimidine ring in CpG dinucleotides, is the the periumbilical level at both sides of the body by needle bi- best understood epigenetic modification. The methylation of opsy under local anesthesia (20 mg xylocaine/mL) (18–20). CpG sites disrupts the binding of transcription factors and at- One hundred thirty-seven women were recruited and com- tracts methyl-binding proteins that are associated with gene si- pleted the 6-mo weight-loss program. Baseline and post- lencing and chromatin compaction (14). Because CpG intervention adipose tissue biopsy samples were available for 29 dinucleotide methylation is associated with the regulation of of these women. Consent for biopsy was an optional part of the gene expression, altered DNA methylation could explain in- larger study. There was no other criteria to be met to be included terindividual phenotypic differences (15). in the biopsy subsample. Fourteen women were further selected We report here the results of the first comprehensive analysis of for the current study based on their response to the caloric re- epigenomic and transcriptomic responses in subcutaneous adi- striction. Women who lost 3% of their body fat were consid- pose tissue after a caloric restriction intervention in overweight ered “high responders,” whereas those who lost ,3% of their and obese women. We found that although both DNA methyl- body fat were considered “low responders” to the caloric re- ation and gene expression differences existed between the high striction. Low (n = 7) and high (n = 7) responders were matched and low responders to dietary restriction after the intervention, for baseline age, BMI, percentage body fat, resting blood only epigenetic differences exist before dieting. These data pressure, fasting blood lipids, glucose and insulin concen- suggest that the epigenetic profile has the potential to differentiate trations, and changes in fat-free mass (Tables 1 and 2). between good and poor responders to caloric restriction. Anthropometric and metabolic measurements SUBJECTS AND METHODS Standardized procedures were used to measure body weight, height, waist girth, resting blood pressure, and blood lipid, Study population and experimental design glucose, and insulin concentrations, as previously described (16, The sample used in this study was a subsample of a larger 17). Total energy expenditure was measured by using the doubly weight-loss study (n = 137) aimed at exploring the effect of labeled water technique (21), and resting metabolic rate was a caloric restriction intervention on body composition, energy measured by indirect calorimetry (16, 17). Total fat mass and fat- expenditure, insulin sensitivity, and metabolic, inflammatory, free mass were measured by dual-energy X-ray absorptiometry hormonal, and psychosocial profiles in overweight and obese (16, 17). postmenopausal women. The recruitment for the larger study began in May 2003. The
Load more

Recommended publications
  • University of California, San Diego
    UNIVERSITY OF CALIFORNIA, SAN DIEGO The post-terminal differentiation fate of RNAs revealed by next-generation sequencing A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Biomedical Sciences by Gloria Kuo Lefkowitz Committee in Charge: Professor Benjamin D. Yu, Chair Professor Richard Gallo Professor Bruce A. Hamilton Professor Miles F. Wilkinson Professor Eugene Yeo 2012 Copyright Gloria Kuo Lefkowitz, 2012 All rights reserved. The Dissertation of Gloria Kuo Lefkowitz is approved, and it is acceptable in quality and form for publication on microfilm and electronically: __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ Chair University of California, San Diego 2012 iii DEDICATION Ma and Ba, for your early indulgence and support. Matt and James, for choosing more practical callings. Roy, my love, for patiently sharing the ups and downs of this journey. iv EPIGRAPH It is foolish to tear one's hair in grief, as though sorrow would be made less by baldness. ~Cicero v TABLE OF CONTENTS Signature Page .............................................................................................................. iii Dedication ....................................................................................................................
    [Show full text]
  • Identification of Novel Sleep Related Genes from Large Scale Phenotyping Experiments in Mice
    University of Kentucky UKnowledge Theses and Dissertations--Biology Biology 2017 IDENTIFICATION OF NOVEL SLEEP RELATED GENES FROM LARGE SCALE PHENOTYPING EXPERIMENTS IN MICE Shreyas Joshi University of Kentucky, [email protected] Digital Object Identifier: https://doi.org/10.13023/ETD.2017.159 Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Joshi, Shreyas, "IDENTIFICATION OF NOVEL SLEEP RELATED GENES FROM LARGE SCALE PHENOTYPING EXPERIMENTS IN MICE" (2017). Theses and Dissertations--Biology. 42. https://uknowledge.uky.edu/biology_etds/42 This Doctoral Dissertation is brought to you for free and open access by the Biology at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Biology by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known.
    [Show full text]
  • Literature Mining Sustains and Enhances Knowledge Discovery from Omic Studies
    LITERATURE MINING SUSTAINS AND ENHANCES KNOWLEDGE DISCOVERY FROM OMIC STUDIES by Rick Matthew Jordan B.S. Biology, University of Pittsburgh, 1996 M.S. Molecular Biology/Biotechnology, East Carolina University, 2001 M.S. Biomedical Informatics, University of Pittsburgh, 2005 Submitted to the Graduate Faculty of School of Medicine in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2016 UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE This dissertation was presented by Rick Matthew Jordan It was defended on December 2, 2015 and approved by Shyam Visweswaran, M.D., Ph.D., Associate Professor Rebecca Jacobson, M.D., M.S., Professor Songjian Lu, Ph.D., Assistant Professor Dissertation Advisor: Vanathi Gopalakrishnan, Ph.D., Associate Professor ii Copyright © by Rick Matthew Jordan 2016 iii LITERATURE MINING SUSTAINS AND ENHANCES KNOWLEDGE DISCOVERY FROM OMIC STUDIES Rick Matthew Jordan, M.S. University of Pittsburgh, 2016 Genomic, proteomic and other experimentally generated data from studies of biological systems aiming to discover disease biomarkers are currently analyzed without sufficient supporting evidence from the literature due to complexities associated with automated processing. Extracting prior knowledge about markers associated with biological sample types and disease states from the literature is tedious, and little research has been performed to understand how to use this knowledge to inform the generation of classification models from ‘omic’ data. Using pathway analysis methods to better understand the underlying biology of complex diseases such as breast and lung cancers is state-of-the-art. However, the problem of how to combine literature- mining evidence with pathway analysis evidence is an open problem in biomedical informatics research.
    [Show full text]
  • University of California, San Diego
    UC San Diego UC San Diego Electronic Theses and Dissertations Title The post-terminal differentiation fate of RNAs revealed by next-generation sequencing Permalink https://escholarship.org/uc/item/7324r1rj Author Lefkowitz, Gloria Kuo Publication Date 2012 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA, SAN DIEGO The post-terminal differentiation fate of RNAs revealed by next-generation sequencing A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Biomedical Sciences by Gloria Kuo Lefkowitz Committee in Charge: Professor Benjamin D. Yu, Chair Professor Richard Gallo Professor Bruce A. Hamilton Professor Miles F. Wilkinson Professor Eugene Yeo 2012 Copyright Gloria Kuo Lefkowitz, 2012 All rights reserved. The Dissertation of Gloria Kuo Lefkowitz is approved, and it is acceptable in quality and form for publication on microfilm and electronically: __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ Chair University of California, San Diego 2012 iii DEDICATION Ma and Ba, for your early indulgence and support. Matt and James, for choosing more practical callings. Roy, my love, for patiently sharing the ups and downs
    [Show full text]
  • DNASE1L2 (A-14): Sc-68312
    SAN TA C RUZ BI OTEC HNOL OG Y, INC . DNASE1L2 (A-14): sc-68312 BACKGROUND APPLICATIONS DNASE1L2 (deoxyribonuclease I-like 2), also known as DHP1 or DNAS1L2, is a DNASE1L2 (A-14) is recommended for detection of DNASE1L2 of human 299 amino acid secreted protein that is expressed in brain tissue and shares origin by Western Blotting (starting dilution 1:200, dilution range 1:100- sequence similarity with DNase I, suggesting a possibly role in DNA hydroly - 1:1000), immunoprecipitation [1-2 µg per 100-500 µg of total protein (1 ml sis. The gene encoding DNASE1L2 maps to human chromosome 16, which of cell lysate)], immunofluorescence (starting dilution 1:50, dilution range encodes over 900 genes and comprises nearly 3% of the human genome. The 1:50-1:500) and solid phase ELISA (starting dilution 1:30, dilution range GAN gene is located on chromosome 16 and, with mutation, may lead to giant 1:30- 1:3000). axonal neuropathy, a nervous system disorder characterized by increasing Suitable for use as control antibody for DNASE1L2 siRNA (h): sc-77320, malfunction with growth. The rare disorder Rubinstein-Taybi syndrome is also DNASE1L2 shRNA Plasmid (h): sc-77320-SH and DNASE1L2 shRNA (h) associated with chromosome 16, as is Crohn’s disease, which is a gastroin - Lentiviral Particles: sc-77320-V. testinal inflammatory condition. Molecular Weight (predicted) of DNASE1L2: 33 kDa. REFERENCES Molecular Weight (observed) of DNASE1L2: 37 kDa. 1. Rodriguez, A.M., Rodin, D., Nomura, H., Morton, C.C., Weremowicz, S. and Positive Controls: IMR-32 nuclear extract: sc-2148.
    [Show full text]
  • WO 2019/046815 Al 07 March 2019 (07.03.2019) W 1P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2019/046815 Al 07 March 2019 (07.03.2019) W 1P O PCT (51) International Patent Classification: OSTERTAG, Eric [US/US]; 4242 Campus Point Court, C12N 15/90 (2006.01) Suite 700, San Diego, California 82121 (US). RICHTER, Maximilian [US/US]; 473 1Kansas Street, San Diego, Cal¬ (21) International Application Number: ifornia 921 16 (US). CRANERT, Stacey Ann [US/US]; PCT/US20 18/049257 7693 Palmilla Dr. Apt. 2103, San Diego, California 92122 (22) International Filing Date: (US). 31 August 2018 (3 1.08.2018) (74) Agent: MILLER, Katherine J. et al.; COOLEY LLP, (25) Filing Language: English 1299 Pennsylvania Avenue, NW, Suite 700, Washington, District of Columbia 20004 (US). (26) Publication Language: English (81) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of national protection available): AE, AG, AL, AM, 62/552,861 31 August 2017 (3 1.08.2017) US AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 62/558,286 13 September 2017 (13.09.2017) US CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, 62/608,546 20 December 2017 (20. 12.2017) US DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (71) Applicant: POSEIDA THERAPEUTICS, INC. HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, [US/US]; 4242 Campus Point Court, Suite 700, San Diego, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, California 92121 (US).
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2004/0138156A1 Schneider Et Al
    US 20040138156A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0138156A1 Schneider et al. (43) Pub. Date: Jul. 15, 2004 (54) THERAPEUTIC REGULATION OF Publication Classification DEOXYRIBONUCLEASE-1-LIKE-3 ACTIVITY (51) Int. Cl." ......................... A61K 48/00; A61K 9/127; C12N 15/88; A61K 38/21 (52) U.S. Cl. ............................ 514/44; 435/458; 424/450; (76) Inventors: Michael C. Schneider, Springfield, IL 424/85.6 (US); Andrew Wilber, Springfield, IL (57) ABSTRACT (US) Deoxyribonuclase 1-like 3 (D3) hydrolyzes lipid-complexed Correspondence Address: DNA and decreases transfection efficiency in liposomal FITCH EVEN TABN AND FLANNERY transfection (lipofection) Systems. Accordingly, D1 L3 pro 120 SOUTH LASALLE STREET vides a more accurate test of the efficiency of lipid/liposomal SUTE 1600 based gene therapy than current Standards using deoxyribo CHICAGO, IL 60603-3406 (US) nuclease 1 (D1). Moreover, it has been found that mice with Systemic lupus erythematosus (lupus) have lowered D1 L3 (21) Appl. No.: 10/378,098 activity. Therefore, differing therapeutic benefits may result from either the upward or downward therapeutic regulation (22) Filed: Feb. 26, 2003 of D1 L3 activity. For example, blocking D1 L3 activity enhances liposomal transfection for gene therapy, while Related U.S. Application Data increasing D1 L3 activity may enhance destruction of patho genic DNA, whether viral, bacterial or endogenous. (60) Provisional application No. 60/359,619, filed on Feb. Destruction of pathogenic DNA may provide treatment for 26, 2002. lupus, or viral and oncogenic diseases. Patent Application Publication Jul. 15, 2004 Sheet 1 of 23 US 2004/0138156A1 DNASE1L3 MSRELAPLLLLLLSIHSALAMRICSFNVRSFGESKQEDKNAMDVIVKWIKRCDIILVM DNAS1L2 MGGPRALLAALWALEAA.
    [Show full text]
  • In a Single Wei Inset Patent Application Publication Aug
    US 20150217131A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0217131 A1 Titova et al. (43) Pub. Date: Aug. 6, 2015 (54) TERAHERTZ PULSE RADATION IN Publication Classification TREATING SKINDSORDERS (51) Int. Cl. (71) Applicants: The Governors of the University of A6IN5/06 (2006.01) Alberta, Edmonton (CA); The (52) U.S. Cl. University of Lethbridge, Lethbridge CPC ......... A61N5/0616 (2013.01); A61N 2005/066 (CA) (2013.01) (72) Inventors: Lyubov Titova, Edmonton (CA); Frank Hegmann, Edmonton (CA); Olga (57) ABSTRACT Kovalchuk, Lethbridge, (CA) (21) Appl. No.: 14/615,153 The disclosure provides methods for the treatment of skin disorders through the use of minimally invasive terahertz (22) Filed: Feb. 5, 2015 radiation. The method includes exposing skin cells to tera hertz radiation in amount Sufficient to modulate gene expres Related U.S. Application Data sion in the skin cells. The modulation of gene expression then (60) Provisional application No. 61/936,627, filed on Feb. results in a reduction of the disease state or aspects thereof in 6, 2014. the exposed skin cells. S.. R S S. & S. S. S. S. & S. S. S.s S ŠS. S.S. ^x S.S. & S.N SS. S.S S S. S S S S R S. Ski SS 8 in a single wei inset Patent Application Publication Aug. 6, 2015 Sheet 1 of 60 US 2015/0217131 A1 º?%-?.- & & cy Figure 1A Figure 1B Figure 1C Patent Application Publication Aug. 6, 2015 Sheet 2 of 60 US 2015/0217131 A1 Staturn E. S as Figure 1D S S.
    [Show full text]
  • Download File
    Failure to process chromatin on apoptotic microparticles in the absence of deoxyribonuclease 1 like 3 drives the development of systemic lupus erythematosus Benjamin Sally Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2017 © 2017 Benjamin Sally All rights reserved ABSTRACT Failure to process chromatin on apoptotic microparticles in the absence of deoxyribonuclease 1 like 3 drives the development of systemic lupus erythematosus Benjamin Sally Systemic lupus erythematosus is an autoinflammatory disorder driven by the development of autoantibodies to self-nucleic acids, in particular to DNA and to chromatin. Loss-of-function mutations of the secreted deoxyribonuclease DNASE1L3 have been implicated in the development of aggressive familial lupus. In addition, recent genome-wide association studies have linked a hypomorphic variant of DNASE1L3 to sporadic lupus. Studies in the lab determined that Dnase1l3-deficient mice develop rapid autoantibody responses against dsDNA and chromatin, and at older ages this leads to a lupus-like inflammatory disease. These disease manifestations were completely independent of the intracellular DNA sensor STING, which has been implicated in other examples of self-DNA driven autoinflammatory diseases. My project focused on developing assays to track the activity of DNASE1L3, as well as identifying the endogenous source of self-DNA normally processed by DNASE1L3. Using mouse models that allow the depletion of specific cell populations, we found that circulating DNASE1L3 is produced by hematopoietic cells, in particular by CD11c+ dendritic cells and by tissue macrophages. Taking into account the unique properties of DNASE1L3, we discovered that this enzyme is uniquely able to digest chromatin contained within and on the surface of apoptotic microparticles.
    [Show full text]
  • Identification of Genes Required for Eye Development by High-Throughput Screening of Mouse Knockouts
    Corrected: Author correction ARTICLE DOI: 10.1038/s42003-018-0226-0 OPEN Identification of genes required for eye development by high-throughput screening of mouse knockouts Bret A. Moore et al.# 1234567890():,; Despite advances in next generation sequencing technologies, determining the genetic basis of ocular disease remains a major challenge due to the limited access and prohibitive cost of human forward genetics. Thus, less than 4,000 genes currently have available phenotype information for any organ system. Here we report the ophthalmic findings from the Inter- national Mouse Phenotyping Consortium, a large-scale functional genetic screen with the goal of generating and phenotyping a null mutant for every mouse gene. Of 4364 genes evaluated, 347 were identified to influence ocular phenotypes, 75% of which are entirely novel in ocular pathology. This discovery greatly increases the current number of genes known to contribute to ophthalmic disease, and it is likely that many of the genes will subsequently prove to be important in human ocular development and disease. Correspondence and requests for materials should be addressed to C.J.M. (email: [email protected]) or to A.M. (email: [email protected]). #A full list of authors and their affiliations appears at the end of the paper. COMMUNICATIONS BIOLOGY | (2018) 1:236 | DOI: 10.1038/s42003-018-0226-0 | www.nature.com/commsbio 1 ARTICLE COMMUNICATIONS BIOLOGY | DOI: 10.1038/s42003-018-0226-0 he prevalence and burden of ophthalmic disease within the genotypes are presented here. Many novel genes previously Thuman population, some with the potential for causing unknown to be involved with mammalian ophthalmic diseases complete blindness, highlights the need to identify factors are presented, demonstrating successful identification of mouse that cause such conditions1–3.
    [Show full text]
  • Genetics in Medicine
    Genetics in Medicine A new microdeletion syndrome involving TBC1D24, ATP6V0C and PDPK1 causes epilepsy, microcephaly and developmental delay. --Manuscript Draft-- Manuscript Number: GIM-D-18-00378R2 Article Type: Article Section/Category: Clinical Genetics Keywords: TBC1D24; microdeletion; microcephaly; Epilepsy; seizures; 16p13.3 Corresponding Author: Philippe Campeau, M.D. Universite de Montreal Montreal, CANADA First Author: Bettina E Mucha, M.D. Order of Authors: Bettina E Mucha, M.D. Siddarth Banka, M.D. Norbert Fonya Ajeawung, Ph.D. Sirinart Molidperee Gary G Chen, Ph.D. Mary Kay Koenig, M.D. Rhamat B Adejumo, M.D. Marianne Till, M.D. Michael Harbord, M.D. Renee Perrier, M.D. Emmanuelle Lemyre, M.D. Renee Myriam Boucher, M.D. Brian G Skotko, M.D. Jessica L Waxler Mary Ann Thomas, M.D. Jennelle C Hodge, Ph.D. Jozef Gecz, M.D. Jillian Nicholl, M.D. Lesley McGregor, M.D. Tobias Linden, M.D. Sanjay M Sisodiya, M.D. Damien Sanlaville, M.D. Sau W Cheung, Ph.D. Carl Ernst, Ph.D. Philippe Campeau, M.D. Manuscript Region of Origin: CANADA Abstract: Purpose: Contiguous gene deletions are known to cause several neurodevelopmental syndromes, many of which are caused by recurrent events on chromosome 16. However, chromosomal microarray studies (CMA) still yield copy number variants Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation (CNV) of unknown clinical significance. We sought to characterize eight individuals with overlapping 205 kb to 504 kb 16p13.3 microdeletions that are distinct from previously published deletion syndromes. Methods: Clinical information on the patients and bioinformatic scores for the deleted genes were analyzed.
    [Show full text]
  • 2-Tesis LG-Correcciones Censor
    Facultad de Farmacia y Nutrición Nutrigenetic approaches for personalized management of obesity and metabolic syndrome traits Enfoques nutrigenéticos para el tratamiento personalizado de la obesidad y componentes del síndrome metabólico Leticia Goñi Mateos Pamplona, 2017 Facultad de Farmacia y Nutrición Memoria presentada por Dña. Leticia Goñi Mateos para aspirar al grado de Doctor por la Universidad de Navarra. Leticia Goñi Mateos El presente trabajo ha sido realizado bajo nuestra dirección en el Departamento de Ciencias de la Alimentación y Fisiología de la Facultad de Farmacia y Nutrición de la Universidad de Navarra y autorizamos su presentación ante el Tribunal que lo ha de juzgar. Pamplona, 14 de septiembre de 2017 VºBº Director VºBº Co-Director Prof. J. Alfredo Martínez Hernández Dr. Marta Cuervo Zapatel Este trabajo ha sido posible gracias a la financiación de diversas entidades: Gobierno de Navarra (Aditech PT025), Ministerio de Economía y Competitividad (AGL2013-45554-R), Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn) Instituto de Salud Carlos III (ISCIII), Centro de Investigación en Nutrición (Universidad de Navarra). La investigación que ha dado lugar a estos resultados ha sido impulsada por la beca predoctoral 2012-2014 de la Asociación de Amigos de la Universidad de Navarra y las becas predoctoral 2015-2017 y de movilidad del Ministerio de Educación, Cultura y Deporte. A mi familia - AGRADECIMIENTOS / ACKNOWLEDGMENTS - A continuación, quisiera plasmar mi agradecimiento a todas aquellas personas e instituciones que han hecho que hoy esté escribiendo estas líneas. A nivel institucional quisiera agradecer a la Universidad de Navarra y a la Facultad de Farmacia y Nutrición que hace ya 10 años decidió acogerme en sus pasillos, aulas y laboratorios.
    [Show full text]