GENETICS AND ETIOLOGY OF DOWN SYNDROME Edited by Subrata Dey Genetics and Etiology of Down Syndrome Edited by Subrata Dey Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access articles distributed under the Creative Commons Non Commercial Share Alike Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published articles. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Romina Krebel Technical Editor Teodora Smiljanic Cover Designer Jan Hyrat Image Copyright http://imag-e-nation.webs.com/ First published August, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Genetics and Etiology of Down Syndrome, Edited by Subrata Dey p. cm. ISBN 978-953-307-631-7 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Genetics and Etiology 1 Chapter 1 Genetics of Down Syndrome 3 Thomas Eggermann and Gesa Schwanitz Chapter 2 Etiology of Down Syndrome: Risk of Advanced Maternal Age and Altered Meiotic Recombination for Chromosome 21 Nondisjunction 23 Subrata Kumar Dey and Sujoy Ghosh Chapter 3 Combinatorial Gene Effects on the Neural Progenitor Pool in Down Syndrome 37 Jie Lu and Volney Sheen Chapter 4 Down Syndrome: A Complex and Interactive Genetic Disorder 65 Samantha L. Deitz, Joshua D. Blazek, Jeffrey P. Solzak and Randall J. Roper Chapter 5 Abnormal Folate Metabolism and Maternal Risk for Down Syndrome 97 Érika Cristina Pavarino, Bruna Lancia Zampieri, Joice Matos Biselli and Eny Maria Goloni Bertollo Chapter 6 Down Syndrome Expressed Protein; DSCR-1 Deters Cancer and Septic Inflammation 121 Takashi Minami Chapter 7 Down Syndrome and Vascular Disease: DSCR1 and NFAT Signaling 137 Monica Y. Lee and Brian R. Wamhoff VI Contents Part 2 Down Syndrome Models 157 Chapter 8 Down Syndrome Model of Alzheimer’s Disease: Beyond Trisomy 21Nondisjunction 159 Antoneta Granic and Huntington Potter Chapter 9 Deficiency of Adult Neurogenesis in the Ts65Dn Mouse Model of Down Syndrome 177 Pavel V. Belichenko and Alexander M. Kleschevnikov Part 3 Neurologic, Urologic, Dental and Allergic Disorders 193 Chapter 10 Dermatological Manifestations of Down Syndrome 195 Dominguez-Cruz JJ and Bueno Delgado MA Chapter 11 Down Syndrome and Periodontal Disease 209 Ahmed Khocht Chapter 12 Dysfunctional Voiding of Non-Neurogenic Neurogenic Bladder: A Urological Disorder Associated with Down Syndrome 231 Narihito Seki and Nouval Shahab Chapter 13 Down Syndrome and Epilepsy 241 A. Nascimento and C. Ortez-González Chapter 14 Endocrine and Autonomic Nervous Adaptations during Physical Exercise in Down Syndrome 259 Véronique ~ Aurélie Bricout Chapter 15 Language and Visuospatial Abilities in Down Syndrome Phenotype: A Cognitive Neuroscience Perspective 275 George Grouios and Antonia Ypsilanti Part 4 Prenatal Diagnosis and Screening 287 Chapter 16 Prenatal Diagnosis of Down Syndrome 289 Myungshin Kim, Jong Chul Shin and In Yang Park Chapter 17 First Trimester Screening for Trisomy 21 by Maternal Age, Nuchal Translucency and Fetal Nasal Bone in Unselected Pregnancies 301 Ksenija Gersak, Maja Pohar-Perme and Darija M. Strah Chapter 18 Noninvasive Prenatal Nucleic Acid Diagnostics of Down Syndrome 313 Radek Vodicka, Radek Vrtel, Jana Böhmova, Romana Kratochvilova, Ladislav Dusek, Ishraq Dhaifalah and Jiri Santavy Preface This book provides the recent developments and advances in research on Down syndrome. It also covers a wide range of topics, including investigations on neurologic, urologic, dental and allergic disorders in Down syndrome. Chromosomal aneuploidy is the leading cause of fetal death in our species and the information about chromosomal nondisjunction in man largely comes from studies in trisomy 21 or Down syndrome, the most frequent of the autosomal trisomies in liveborns. The cause of nondisjunction of chromosome 21 remains largely unknown. Accurate investigations on meiotic nondisjunction have been made possible in recent years by the development and utilization of microsatellite markers. Although several hypotheses have been put forward, it is still unclear as to whether particular gene loci on chromosome 21 are sufficient to cause Down syndrome and its associated features. For over two decades trisomy 21 has represented a prototype disorder for the study of human aneuploidy and copy-number variation, but the genes responsible for most Down syndrome phenotypes are still unknown. The genetic mechanism by which wide variability in the phenotypes arise is not understood, additional complexity may exist due to possible epigenetic changes that may act differently on Down syndrome. Consequently, gene-disease links have often been based on indirect evidence from cellular or animal models. Numerous mouse models with features reminiscent of those seen in individuals with Down syndrome have been produced and studied in some depth, and these have added considerable insight into possible genetic mechanisms by which trisomy 21 leads to Down syndrome. The book is organized into four sections. All sections include chapters on recent advances in Down syndrome research. Section I deals with our present knowledge on the genetics and etiology of Down syndrome. Section II discusses the utility of using mouse model for in depth study of Down syndrome. Down syndrome could be used as model for understanding the genetics of Alzheimer’s disease. Section III describes the etiology and clinical aspects of some common disorders of Down syndrome patients such as neurologic, urologic, dental and allergic disorders. X Preface Section IV focuses on prenatal diagnosis and screening of Down syndrome. This book provides a concise yet comprehensive source of current information on Down syndrome. Research workers, scientists, medical graduates and paediatricians will find it an excellent source for reference and review. Acknowledgements The editor wants to acknowledge the superb assistance of staff members and management of InTech Publisher. In particular, Ms. Romina Krebel for her co- ordination and editorial assistance. We are grateful to all contributing authors and scientists who made this book possible by providing valuable research and review papers. Subrata Dey Salt Lake City, Kolkata, India [...]... 47-48 22 Genetics and Etiology of Down Syndrome Wyandt, H.E., Tonk, V.S (2004) Atlas of human chromosome heteromorphisms Kluwer Academic Publishers, Dordrecht/NL 2 Etiology of Down Syndrome: Risk of Advanced Maternal Age and Altered Meiotic Recombination for Chromosome 21 Nondisjunction 1School Subrata Kumar Dey1 and Sujoy Ghosh1,2 of Biotechnology & Biological Sciences, West Bengal University of Technology,... descending order of size and of the position of the centromere According to the type of induced banding pattern, two subtypes can be defined: a) those resulting in bands distributed along the length of the whole chromosome, such as G-, Q- and R-bands, and b) those that stain specific chromosome structures (e.g C-bands, nucleolus organizing regions, telomeric bands)(Shaffer et al., 2009) The advantage of classical... end of the short arm (p) The short arm 21p is heterochromatic but consists of different types of repetitive DNA (Figure 1)(Wyandt and Tonk, 2004) The relative length of the short arm of chromosome 21 comprises 30 % of its total length (Figure 1) Variants in brilliant fluorescence after QFQ-staining are diagnosed in 2.0 % of band p11.2 and 10.0 % of band p13 Duplications in p12 show a frequency of 0.7-1.3... predominance of standard trisomy 21 as the cause of DS, further types of aberrations exist They differ in relation to the type of abnormality, and they lead to different prognoses as to the chances of development of the carrier and recurrence risks for the relatives of a carrier Therefore, the indication for a chromosome analysis is always given in the presence of the distinct phenotype of DS 3.1 Standard... Part 1 Genetics and Etiology 1 Genetics of Down Syndrome Thomas Eggermann1 and Gesa Schwanitz2 1Institute 2Institute of Human Genetics, RWTH Aachen of Human Genetics, University of Bonn Germany 1 Introduction 1.1 Morphology According to the International System for Human Cytogenetic Nomenclature... The long arm (q) of chromosome 21 is euchromatic, with the exception of the pericentromeric region q11.1 and the distal telomere Chromosomes are usually presented and analysed in the metaphase of mitosis after in vitro cultivation, which is not identical to their appearance in vivo Among the differentiated cells, 4 Genetics and Etiology of Down Syndrome Fig 1 Structure and morphology of chromosome 21... milieu The third and the final risk phase is the maturation of oocyte which is associated with the adverse effect of advancing maternal age on protein components involved in 24 Genetics and Etiology of Down Syndrome chromosome separation system and rapidly deteriorating endocrine environments In contrast, spermatogenesis begins at puberty and spermatogonial cells complete both MI and MII without any... are tissue-specific and are only active in certain cell types while being inactivated in others by methylation This gene inactivation is accompanied by a more condensed structure of the 6 Genetics and Etiology of Down Syndrome chromatin and, consequently, the DNA of these genes is not accessible to the transcription factors These AT-rich DNA regions show a higher staining intensity and can thus be localised... one of the three chromosomes 21 of a standard trisomy in a portion of the cells Alternatively, the zygote can have a normal karyotype, but in a postzygotic mitosis, nondisjunction of chromosomes 21 takes place 10 Genetics and Etiology of Down Syndrome Structural aberrations of chromosome 21 as mosaics are always caused by postzygotic rearrangements Carriers of mosaics with the aberrant cells occuring... kind permission of J.R Korenberg) 2 Historic development of the cytogenetics of DS DS was the first malformation complex that could be delineated as a chromosome abnormality in 1959 This was enabled by the new technology to prepare chromosomes in Genetics of Down Syndrome 7 the metaphase of mitosis In the early years, mitoses were analysed after direct preparations of bone marrow cells and long term . GENETICS AND ETIOLOGY OF DOWN SYNDROME Edited by Subrata Dey Genetics and Etiology of Down Syndrome Edited by Subrata Dey . Down syndrome research. Section I deals with our present knowledge on the genetics and etiology of Down syndrome. Section II discusses the utility of using mouse model for in depth study of. depth study of Down syndrome. Down syndrome could be used as model for understanding the genetics of Alzheimer’s disease. Section III describes the etiology and clinical aspects of some common