DOCSLIB.ORG

Role of Genomic Copy Number Variation in Alzheimer's Disease And

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

ROLE OF GENOMIC COPY NUMBER VARIATION IN ALZHEIMER'S DISEASE AND MILD COGNITIVE IMPAIRMENT Shanker Swaminathan Submitted to the faculty of the University Graduate School in partial fulfillment of the requirements for the degree Doctor of Philosophy in the Department of Medical and Molecular Genetics, Indiana University August 2012 Accepted by the Faculty of Indiana University, in partial fulfillment of the requirements for the Degree of Doctor of Philosophy. ____________________________________ Andrew J. Saykin, PsyD, Chair ____________________________________ Tatiana Foroud, PhD Doctoral Committee ____________________________________ John I. Nurnberger, Jr, MD, PhD May 23, 2012 ____________________________________ Li Shen, PhD ii To my parents and sister iii ACKNOWLEDGEMENTS This work would not have been possible without the help and support of a lot of people. I would like to thank Dr. Andrew Saykin, my thesis advisor, for providing me the opportunity to be a part of his lab and be able to pursue research in the field of imaging genetics. Dr. Saykin has always encouraged me to be pursue new information and be up to date with the current developments in the field. He has been a constant source of support and guidance and was a person whom I could always turn to when I have had problems. His feedback and suggestions have been very helpful. I would also like to thank the members of my research committee: Drs. Tatiana Foroud, John Nurnberger and Li Shen for their help in this work. They encouraged me to pursue this work and offered feedback and suggestions which were very helpful. They also made sure that I was on track with the program requirements and was making smooth progress towards the PhD degree. I would like to thank other members of the lab including Dr. Li Shen, Dr. Sungeun Kim, Dr. Kwangsik Nho, Dr. Shannon Risacher, Susan Conroy, John West, Jing Wan, Kelley Holohan and Vijay Ramanan for their help with this work. I was fortunate to work with them on a number of projects, which enabled me to learn some of the methods used in imaging analyses and genetic analyses. I am also grateful to Dr. Mark Inlow for his help and guidance on the statistical analyses. I would also like to thank the faculty and staff at the Center for Neuroimaging. I express my gratitude to Dr. Kenneth Cornetta, Dr. Brittney-Shea Herbert, Dr. Terry Reed and Peggy Knople for their guidance on the program requirements and for making sure I was completing the requirements in a timely manner. I also thank the faculty and iv staff at the Department of Medical and Molecular Genetics as well as the staff of the IUPUI Graduate Office and the Graduate Division of the Indiana University School of Medicine for their help during the course of my study. Finally, I would like to offer my heartfelt thanks to my family. They encouraged me to pursue my interests in performing research and were there with me at every step. They follow my progress keenly and are very interested in learning about the various projects I am involved in as well the Genetics field in general. Their motivation and support has helped me progress along smoothly and I would like to express my sincere gratitude to them. v ABSTRACT Shanker Swaminathan ROLE OF GENOMIC COPY NUMBER VARIATION IN ALZHEIMER'S DISEASE AND MILD COGNITIVE IMPAIRMENT Alzheimer's disease (AD) is the most common form of dementia defined by loss in memory and cognitive abilities severe enough to interfere significantly with daily life activities. Amnestic mild cognitive impairment (MCI) is a clinical condition in which an individual has memory deficits not normal for the individual's age, but not severe enough to interfere significantly with daily functioning. Every year, approximately 10-15% of individuals with MCI will progress to dementia. Currently, there is no treatment to slow or halt AD progression, but research studies are being conducted to identify causes that can lead to its earlier diagnosis and treatment. Genetic variation plays a key role in the development of AD, but not all genetic factors associated with the disease have been identified. Copy number variants (CNVs), a form of genetic variation, are DNA regions that have added genetic material (duplications) or loss of genetic material (deletions). The regions may overlap one or more genes possibly affecting their function. CNVs have been shown to play a role in certain diseases. At the start of this work, only one published study had examined CNVs in late-onset AD and none had examined MCI. In order to determine the possible involvement of CNVs in AD and MCI susceptibility, genome-wide CNV analyses were performed in participants from three cohorts: the ADNI cohort, the NIA-LOAD/NCRAD Family Study cohort, and a vi unique cohort of clinically characterized and neuropathologically verified individuals. Only participants with DNA samples extracted from blood/brain tissue were included in the analyses. CNV calls were generated using genome-wide array data available on these samples. After detailed quality review, case (AD and/or MCI)/control association analyses including candidate gene and genome-wide approaches were performed. Although no excess CNV burden was observed in cases compared to controls in the three cohorts, gene-based association analyses identified a number of genes including the AD candidate genes CHRFAM7A, RELN and DOPEY2. Thus, the present work highlights the possible role of CNVs in AD and MCI susceptibility warranting further investigation. Future work will include replication of the findings in independent samples and confirmation by molecular validation experiments. Andrew J. Saykin, PsyD, Chair vii TABLE OF CONTENTS List of Tables ................................................................................................................... x List of Figures ................................................................................................................ xii List of Abbreviations ..................................................................................................... xiv I. Introduction A. Alzheimer's disease ......................................................................................... 1 B. Role of genetic variation in Alzheimer's disease .............................................. 4 C. Copy number variation .................................................................................. 11 D. Mechanisms for formation of copy number variations .................................... 12 E. Methods for copy number variation detection ................................................ 16 F. Copy number variation detection algorithms .................................................. 20 G. Copy number variation in selected neuropsychiatric disorders ...................... 23 H. Copy number variation in Alzheimer's disease .............................................. 33 I. Statement of purpose ...................................................................................... 35 II. Genomic Copy Number Analysis in Alzheimer's Disease and Mild Cognitive Impairment: An ADNI Study A. Introduction .................................................................................................... 37 B. Methods......................................................................................................... 40 C. Results .......................................................................................................... 47 D. Discussion ..................................................................................................... 59 III. Analysis of Copy Number Variation in Alzheimer's Disease: the NIA-LOAD/NCRAD Family Study A. Introduction .................................................................................................... 65 B. Methods......................................................................................................... 68 C. Results .......................................................................................................... 75 viii D. Discussion ..................................................................................................... 88 IV. Analysis of Copy Number Variation in Alzheimer's Disease in a Cohort of Clinically Characterized and Neuropathologically Verified Individuals A. Introduction .................................................................................................... 97 B. Methods......................................................................................................... 99 C. Results ........................................................................................................ 104 D. Discussion ................................................................................................... 116 V. Summary and Future Directions .............................................................................. 120 References .................................................................................................................. 127 Curriculum Vitae ix LIST OF TABLES 1. Genes associated with early-onset familial Alzheimer's disease .................................. 6 2. Summary of published genome-wide association studies in Alzheimer's disease ............................................................................................................................7 3. Examples of copy number variations and selected neuropsychiatric disorders ......................................................................................................................
Recommended publications
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus

    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.
  • Transcriptional Regulation, Role in Inflammation and Potential Pharmacological Implications

    Transcriptional Regulation, Role in Inflammation and Potential Pharmacological Implications

    UNIVERSITA’ DEGLI STUDI DI MILANO Dipartimento di Biotecnologie Mediche e Medicina Traslazionale Scuola di dottorato in Medicina Sperimentale e Biotecnologie Mediche Ciclo XXIX THE HUMAN-RESTRICTED DUPLICATED FORM OF THE α7 NICOTINIC ACETYLCHOLINE RECEPTOR, CHRFAM7A: TRANSCRIPTIONAL REGULATION, ROLE IN INFLAMMATION AND POTENTIAL PHARMACOLOGICAL IMPLICATIONS. Settore disciplinare: Bio/14 Tesi di dottorato di: Annalisa Maroli Relatore: Prof.ssa Grazia Pietrini Coordinatore: Prof. Massimo Locati Anno accademico: 2016-2017 1 2 Contents Abstract ................................................................................................................................. 5 1. Introduction ................................................................................................................... 7 1.1. Inflammation........................................................................................................... 7 1.1.1. Acute inflammation ......................................................................................... 7 1.1.2. Molecular mechanisms of acute inflammation ............................................... 9 1.1.3. Resolution of acute inflammation ................................................................. 13 1.1.4. Chronic inflammation .................................................................................... 14 1.2. The Cholinergic Anti-Inflammatory Pathway........................................................ 14 1.3. The α7 nicotinic acetylcholine receptor ..............................................................
  • Investigation of Copy Number Variations on Chromosome 21 Detected by Comparative Genomic Hybridization

    Investigation of Copy Number Variations on Chromosome 21 Detected by Comparative Genomic Hybridization

    Li et al. Molecular Cytogenetics (2018) 11:42 https://doi.org/10.1186/s13039-018-0391-3 RESEARCH Open Access Investigation of copy number variations on chromosome 21 detected by comparative genomic hybridization (CGH) microarray in patients with congenital anomalies Wenfu Li, Xianfu Wang and Shibo Li* Abstract Background: The clinical features of Down syndrome vary among individuals, with those most common being congenital heart disease, intellectual disability, developmental abnormity and dysmorphic features. Complex combination of Down syndrome phenotype could be produced by partially copy number variations (CNVs) on chromosome 21 as well. By comparing individual with partial CNVs of chromosome 21 with other patients of known CNVs and clinical phenotypes, we hope to provide a better understanding of the genotype-phenotype correlation of chromosome 21. Methods: A total of 2768 pediatric patients sample collected at the Genetics Laboratory at Oklahoma University Health Science Center were screened using CGH Microarray for CNVs on chromosome 21. Results: We report comprehensive clinical and molecular descriptions of six patients with microduplication and seven patients with microdeletion on the long arm of chromosome 21. Patients with microduplication have varied clinical features including developmental delay, microcephaly, facial dysmorphic features, pulmonary stenosis, autism, preauricular skin tag, eye pterygium, speech delay and pain insensitivity. We found that patients with microdeletion presented with developmental delay, microcephaly, intrauterine fetal demise, epilepsia partialis continua, congenital coronary anomaly and seizures. Conclusion: Three patients from our study combine with four patients in public database suggests an association between 21q21.1 microduplication of CXADR gene and patients with developmental delay. One patient with 21q22.13 microdeletion of DYRK1A shows association with microcephaly and scoliosis.
  • Whole Exome Sequencing in ADHD Trios from Single and Multi-Incident Families Implicates New Candidate Genes and Highlights Polygenic Transmission

    Whole Exome Sequencing in ADHD Trios from Single and Multi-Incident Families Implicates New Candidate Genes and Highlights Polygenic Transmission

    European Journal of Human Genetics (2020) 28:1098–1110 https://doi.org/10.1038/s41431-020-0619-7 ARTICLE Whole exome sequencing in ADHD trios from single and multi-incident families implicates new candidate genes and highlights polygenic transmission 1,2 1 1,2 1,3 1 Bashayer R. Al-Mubarak ● Aisha Omar ● Batoul Baz ● Basma Al-Abdulaziz ● Amna I. Magrashi ● 1,2 2 2,4 2,4,5 6 Eman Al-Yemni ● Amjad Jabaan ● Dorota Monies ● Mohamed Abouelhoda ● Dejene Abebe ● 7 1,2 Mohammad Ghaziuddin ● Nada A. Al-Tassan Received: 26 September 2019 / Revised: 26 February 2020 / Accepted: 10 March 2020 / Published online: 1 April 2020 © The Author(s) 2020. This article is published with open access Abstract Several types of genetic alterations occurring at numerous loci have been described in attention deficit hyperactivity disorder (ADHD). However, the role of rare single nucleotide variants (SNVs) remains under investigated. Here, we sought to identify rare SNVs with predicted deleterious effect that may contribute to ADHD risk. We chose to study ADHD families (including multi-incident) from a population with a high rate of consanguinity in which genetic risk factors tend to 1234567890();,: 1234567890();,: accumulate and therefore increasing the chance of detecting risk alleles. We employed whole exome sequencing (WES) to interrogate the entire coding region of 16 trios with ADHD. We also performed enrichment analysis on our final list of genes to identify the overrepresented biological processes. A total of 32 rare variants with predicted damaging effect were identified in 31 genes. At least two variants were detected per proband, most of which were not exclusive to the affected individuals.
  • Supplementary Materials

    Supplementary Materials

    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
  • Analysis of the Indacaterol-Regulated Transcriptome in Human Airway

    Analysis of the Indacaterol-Regulated Transcriptome in Human Airway

    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/04/13/jpet.118.249292.DC1 1521-0103/366/1/220–236$35.00 https://doi.org/10.1124/jpet.118.249292 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:220–236, July 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Analysis of the Indacaterol-Regulated Transcriptome in Human Airway Epithelial Cells Implicates Gene Expression Changes in the s Adverse and Therapeutic Effects of b2-Adrenoceptor Agonists Dong Yan, Omar Hamed, Taruna Joshi,1 Mahmoud M. Mostafa, Kyla C. Jamieson, Radhika Joshi, Robert Newton, and Mark A. Giembycz Departments of Physiology and Pharmacology (D.Y., O.H., T.J., K.C.J., R.J., M.A.G.) and Cell Biology and Anatomy (M.M.M., R.N.), Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Received March 22, 2018; accepted April 11, 2018 Downloaded from ABSTRACT The contribution of gene expression changes to the adverse and activity, and positive regulation of neutrophil chemotaxis. The therapeutic effects of b2-adrenoceptor agonists in asthma was general enriched GO term extracellular space was also associ- investigated using human airway epithelial cells as a therapeu- ated with indacaterol-induced genes, and many of those, in- tically relevant target. Operational model-fitting established that cluding CRISPLD2, DMBT1, GAS1, and SOCS3, have putative jpet.aspetjournals.org the long-acting b2-adrenoceptor agonists (LABA) indacaterol, anti-inflammatory, antibacterial, and/or antiviral activity. Numer- salmeterol, formoterol, and picumeterol were full agonists on ous indacaterol-regulated genes were also induced or repressed BEAS-2B cells transfected with a cAMP-response element in BEAS-2B cells and human primary bronchial epithelial cells by reporter but differed in efficacy (indacaterol $ formoterol .
  • Genome-Wide DNA Methylation Analysis on C-Reactive Protein Among Ghanaians Suggests Molecular Links to the Emerging Risk of Cardiovascular Diseases ✉ Felix P

    Genome-Wide DNA Methylation Analysis on C-Reactive Protein Among Ghanaians Suggests Molecular Links to the Emerging Risk of Cardiovascular Diseases ✉ Felix P

    www.nature.com/npjgenmed ARTICLE OPEN Genome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases ✉ Felix P. Chilunga 1 , Peter Henneman2, Andrea Venema2, Karlijn A. C. Meeks 3, Ana Requena-Méndez4,5, Erik Beune1, Frank P. Mockenhaupt6, Liam Smeeth7, Silver Bahendeka8, Ina Danquah9, Kerstin Klipstein-Grobusch10,11, Adebowale Adeyemo 3, Marcel M.A.M Mannens2 and Charles Agyemang1 Molecular mechanisms at the intersection of inflammation and cardiovascular diseases (CVD) among Africans are still unknown. We performed an epigenome-wide association study to identify loci associated with serum C-reactive protein (marker of inflammation) among Ghanaians and further assessed whether differentially methylated positions (DMPs) were linked to CVD in previous reports, or to estimated CVD risk in the same population. We used the Illumina Infinium® HumanMethylation450 BeadChip to obtain DNAm profiles of blood samples in 589 Ghanaians from the RODAM study (without acute infections, not taking anti-inflammatory medications, CRP levels < 40 mg/L). We then used linear models to identify DMPs associated with CRP concentrations. Post-hoc, we evaluated associations of identified DMPs with elevated CVD risk estimated via ASCVD risk score. We also performed subset analyses at CRP levels ≤10 mg/L and replication analyses on candidate probes. Finally, we assessed for biological relevance of our findings in public databases. We subsequently identified 14 novel DMPs associated with CRP. In post-hoc evaluations, we found 1234567890():,; that DMPs in PC, BTG4 and PADI1 showed trends of associations with estimated CVD risk, we identified a separate DMP in MORC2 that was associated with CRP levels ≤10 mg/L, and we successfully replicated 65 (24%) of previously reported DMPs.
  • Title CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1 Author(S)

    Title CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1 Author(S)

    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by HKU Scholars Hub CNV Analysis in Tourette Syndrome Implicates Large Genomic Title Rearrangements in COL8A1 and NRXN1 Nag, A; Bochukova, EG; Kremeyer, B; Campbell, DD; et al.,; Author(s) Ruiz-Linares, A Citation PLoS ONE, 2013, v. 8 n. 3 Issued Date 2013 URL http://hdl.handle.net/10722/189374 Rights Creative Commons: Attribution 3.0 Hong Kong License CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1 Abhishek Nag1, Elena G. Bochukova2, Barbara Kremeyer1, Desmond D. Campbell1, Heike Muller1, Ana V. Valencia-Duarte3,4, Julio Cardona5, Isabel C. Rivas5, Sandra C. Mesa5, Mauricio Cuartas3, Jharley Garcia3, Gabriel Bedoya3, William Cornejo4,5, Luis D. Herrera6, Roxana Romero6, Eduardo Fournier6, Victor I. Reus7, Thomas L Lowe7, I. Sadaf Farooqi2, the Tourette Syndrome Association International Consortium for Genetics, Carol A. Mathews7, Lauren M. McGrath8,9, Dongmei Yu9, Ed Cook10, Kai Wang11, Jeremiah M. Scharf8,9,12, David L. Pauls8,9, Nelson B. Freimer13, Vincent Plagnol1, Andre´s Ruiz-Linares1* 1 UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, United Kingdom, 2 University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom, 3 Laboratorio de Gene´tica Molecular, SIU, Universidad de Antioquia, Medellı´n, Colombia, 4 Escuela de Ciencias de la Salud, Universidad Pontificia
  • Nicotine Dependece

    Nicotine Dependece

    Alma Mater Studiorum – Università di Bologna DOTTORATO DI RICERCA IN Biologia Cellulare e Molecolare Ciclo XXX Settore Concorsuale: 05/I1 Settore Scientifico Disciplinare: BIO/18 GENETICA Investigation of genetic risk variants for nicotine dependence and cluster headache Presentata da: Cinzia Cameli Coordinatore Dottorato Supervisore Prof. Giovanni Capranico Prof.ssa Elena Maestrini Co-supervisore Dott.ssa Elena Bacchelli Esame finale anno 2018 TABLE OF CONTENTS ABSTRACT......................................................................................................................... 4 INTRODUCTION ................................................................................................................ 6 CHAPTER 1 Nicotine dependence ...................................................................................... 6 1.1 Biological mechanisms ............................................................................................................ 6 1.2 Nicotinic acetylcholine receptors ............................................................................................ 8 1.2.1 Protein structure ............................................................................................................. 8 1.2.2 Localization and function of neuronal nAChRs ............................................................. 10 1.2.3 α7 nAChRs ..................................................................................................................... 12 1.3 The genetics of nicotine dependence ..................................................................................
  • Uniquely Human CHRFAM7A Gene Increases the Hematopoietic Stem Cell Reservoir in Mice and Amplifies Their Inflammatory Response

    Uniquely Human CHRFAM7A Gene Increases the Hematopoietic Stem Cell Reservoir in Mice and Amplifies Their Inflammatory Response

    UC San Diego UC San Diego Previously Published Works Title Uniquely human CHRFAM7A gene increases the hematopoietic stem cell reservoir in mice and amplifies their inflammatory response. Permalink https://escholarship.org/uc/item/6b96b0tv Journal Proceedings of the National Academy of Sciences of the United States of America, 116(16) ISSN 0027-8424 Authors Costantini, Todd W Chan, Theresa W Cohen, Olga et al. Publication Date 2019-04-03 DOI 10.1073/pnas.1821853116 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Uniquely human CHRFAM7A gene increases the hematopoietic stem cell reservoir in mice and amplifies their inflammatory response Todd W. Costantinia, Theresa W. Chana, Olga Cohena, Simone Langnessa, Sabrina Treadwella, Elliot Williamsa, Brian P. Eliceiria, and Andrew Bairda,1 aDepartment of Surgery, University of California, San Diego, La Jolla, CA 92093 Edited by Lawrence Steinman, Stanford University School of Medicine, Stanford, CA, and approved March 8, 2019 (received for review December 21, 2018) A subset of genes in the human genome are uniquely human and independently regulated by unique promoters that drive their differ- not found in other species. One example is CHRFAM7A, a dominant- ential expression (13, 14). Moreover, several genetic studies have tied the negative inhibitor of the antiinflammatory α7 nicotinic acetylcholine CHRFAM7A/CHRNA7 locus and a 2-bp mutation in CHRFAM7A receptor (α7nAChR/CHRNA7) that is also a neurotransmitter receptor on chromosome 15 to nicotine
  • Abstracts from the 51St European Society of Human Genetics Conference: Electronic Posters

    Abstracts from the 51St European Society of Human Genetics Conference: Electronic Posters

    European Journal of Human Genetics (2019) 27:870–1041 https://doi.org/10.1038/s41431-019-0408-3 MEETING ABSTRACTS Abstracts from the 51st European Society of Human Genetics Conference: Electronic Posters © European Society of Human Genetics 2019 June 16–19, 2018, Fiera Milano Congressi, Milan Italy Sponsorship: Publication of this supplement was sponsored by the European Society of Human Genetics. All content was reviewed and approved by the ESHG Scientific Programme Committee, which held full responsibility for the abstract selections. Disclosure Information: In order to help readers form their own judgments of potential bias in published abstracts, authors are asked to declare any competing financial interests. Contributions of up to EUR 10 000.- (Ten thousand Euros, or equivalent value in kind) per year per company are considered "Modest". Contributions above EUR 10 000.- per year are considered "Significant". 1234567890();,: 1234567890();,: E-P01 Reproductive Genetics/Prenatal Genetics then compared this data to de novo cases where research based PO studies were completed (N=57) in NY. E-P01.01 Results: MFSIQ (66.4) for familial deletions was Parent of origin in familial 22q11.2 deletions impacts full statistically lower (p = .01) than for de novo deletions scale intelligence quotient scores (N=399, MFSIQ=76.2). MFSIQ for children with mater- nally inherited deletions (63.7) was statistically lower D. E. McGinn1,2, M. Unolt3,4, T. B. Crowley1, B. S. Emanuel1,5, (p = .03) than for paternally inherited deletions (72.0). As E. H. Zackai1,5, E. Moss1, B. Morrow6, B. Nowakowska7,J. compared with the NY cohort where the MFSIQ for Vermeesch8, A.
  • Supp Table 6.Pdf

    Supp Table 6.Pdf

    Supplementary Table 6. Processes associated to the 2037 SCL candidate target genes ID Symbol Entrez Gene Name Process NM_178114 AMIGO2 adhesion molecule with Ig-like domain 2 adhesion NM_033474 ARVCF armadillo repeat gene deletes in velocardiofacial syndrome adhesion NM_027060 BTBD9 BTB (POZ) domain containing 9 adhesion NM_001039149 CD226 CD226 molecule adhesion NM_010581 CD47 CD47 molecule adhesion NM_023370 CDH23 cadherin-like 23 adhesion NM_207298 CERCAM cerebral endothelial cell adhesion molecule adhesion NM_021719 CLDN15 claudin 15 adhesion NM_009902 CLDN3 claudin 3 adhesion NM_008779 CNTN3 contactin 3 (plasmacytoma associated) adhesion NM_015734 COL5A1 collagen, type V, alpha 1 adhesion NM_007803 CTTN cortactin adhesion NM_009142 CX3CL1 chemokine (C-X3-C motif) ligand 1 adhesion NM_031174 DSCAM Down syndrome cell adhesion molecule adhesion NM_145158 EMILIN2 elastin microfibril interfacer 2 adhesion NM_001081286 FAT1 FAT tumor suppressor homolog 1 (Drosophila) adhesion NM_001080814 FAT3 FAT tumor suppressor homolog 3 (Drosophila) adhesion NM_153795 FERMT3 fermitin family homolog 3 (Drosophila) adhesion NM_010494 ICAM2 intercellular adhesion molecule 2 adhesion NM_023892 ICAM4 (includes EG:3386) intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)adhesion NM_001001979 MEGF10 multiple EGF-like-domains 10 adhesion NM_172522 MEGF11 multiple EGF-like-domains 11 adhesion NM_010739 MUC13 mucin 13, cell surface associated adhesion NM_013610 NINJ1 ninjurin 1 adhesion NM_016718 NINJ2 ninjurin 2 adhesion NM_172932 NLGN3 neuroligin