Atlas of Human Chromosome Heteromorphisms Atlas of Human Chromosome Heteromorphisms Edited by Herman E.Wyandt,PhD,FACMG Vijay S.Tonk,PhD,FACMB Associate Professor of Pathology Professor of Pediatrics Director of Cytogenetics (with joint appointments in Pathology Center for Human Genetics and in Obstetrics and Gynecology) Boston University School of Medicine Director of Cytogenetics and Medical Boston, Massachusetts, USA Genetics Texas Tech University Health Sciences Center Lubbock, Texas, USA SPRINGER-SCIENCE+BUSINESS MEDIA, B.V. Library of Congress Cataloging-in-Publication Data Atlas of human chromosome heteromorphisms / editors,Herman E. Wyandt and Vijay S. Tonk. p.; cm. Includes index. ISBN 978-90-481-6296-3 ISBN 978-94-017-0433-5 (eBook) DOI 10.1007/978-94-017-0433-5 1. Human chromosomes – Atlases. 2. Chromosome polymorphism – Atlases. I. Wyandt, Herman Edwin,1939– II. Tonk,Vijay S. [DNLM:1. Chromosomes,Human – Atlases.] 2003051681 ISBN 978-90-481-6296-3 Printed on acid-free paper All rights reserved ©2004Springer Science+Business Media Dordrecht Originally published by Kluwer Academic Publishers in 2004 No part of this publication may be reproduced or utilized in any form or by any means,electronic, mechanical,including photocopying,recording or by any information storage and retrieval system, without written permission from the copyright owner. DEDICATION We dedicate this work to our families,to Linda,to Sunita and Sahil,and to Sachi who will not be forgotten. Contents Authors xi Foreword (Aubrey Milunsky) xiii Preface xv Acknowledgements xvii List of Atlas Contributors xix PART I:REVIEW Chapter 1. IntroductionH.Wyandt 3 Definition of heteromorphism, historical review, and purpose of this work Chapter 2. Methods of Studying Human Chromosomes and NomenclatureG.Velagaleti and V.Tonk 11 Basic chromosome morphology, nomenclature, banding and other specialized techniques Chapter 3. Normal Population StudiesH.Wyandt and V.Tonk 33 Variants in non-banded and banded chromosomes, major population studies, racial and ethnic differences Chapter 4. Heteromorphisms in Clinical Populations S.Patil and H.Wyandt 47 Heteromorphisms in mentally retarded populations, in pregnancy loss, in infertility and in cancer Chapter 5. Technical Variables and the Use of Heteromorphisms in the Study of Human Chromosomes. A:Paternity Testing.B:Origin of Chromosome Abnormalities S.Olson and R.Magenis 63 vii CONTENTS Chapter 6. Euchromatic VariantsS.Jalal and R.Ketterling 75 Euchromatic variants due to duplication and deletion. Origin of euchromatic variants Chapter 7. FISH TechnologiesH.Wyandt and V.Tonk 87 Principles and study of heteromorphisms by FISH Chapter 8. Molecular Dissection of Heteromorphic RegionsB.Levy and P.Warburton 97 Satellite DNA, satellite DNA families, satellite DNA and centromere function, satellite DNA and chromosome evolution, syndromes.Minisatellite DNA Chapter 9. Evolution of Human Alpha Satellite Sequences Comprising Variant Centromeric Chromosome RegionsW.Patino, M.Arcos-Burgos and R.Lebo 107 PART II:PLATES Organization of Part II 129 Chromosome 1 (Plates 1–8) 131 Summary and References Chromosome 2 (Plates 9, 10) 143 Summary and References Chromosome 3 (Plate 11) 149 Summary and References Chromosome 4 (Plates 12–14) 153 Summary and References Chromosome 5 (Plates 15–17) 159 Summary and References Chromosome 6 (Plates 18, 19) 164 Summary and References Chromosome 7 (Plate 20) 168 Summary and References Chromosome 8 (Plate 21) 171 Summary and References Chromosome 9 (Plates 22–29) 175 Summary and References Chromosome 10 (Plate 30) 190 Summary and References viii CONTENTS Chromosome 11 (Plates 31, 32) 193 Summary and References Chromosome 12 (Plate 33) 197 Summary and References Chromosome 13 (Plates 34–36) 200 Summary and References Chromosome 14 (Plates 37–40) 206 Summary and References Chromosome 15 (Plates 41–47) 212 Summary and References Chromosome 16 (Plates 48, 49) 223 Summary and References Chromosome 17 (Plate 50) 228 Summary and References Chromosome 18 (Plates 51–53) 232 Summary and References Chromosome 19 (Plate 54) 239 Summary and References Chromosome 20 (Plate 55) 242 Summary and References Chromosome 21 (Plates 56–58) 245 Summary and References Chromosome 22 (Plates 59, 60) 252 Summary and References Chromosome X (Plates 61, 62) 257 Summary and References Chromosome Y (Plates 63–66) 261 Summary and References FISH Variants (Plates 67–69) 270 Index 275 ix Authors Mauricio Arcos-Burgos, PhD Development and Rehabilitation Medical Genetics Branch Center National Institute of Health NIH Oregon Health Sciences University Bethesda, MD, USA Portland, OR, USA Syed M.Jalal, PhD Susan Bennett Olson, PhD Cytogenetics Laboratory Department of Molecular and Division of Laboratory Genetics Medical Genetics Department of Laboratory Oregon Health Sciences University Medicine and Pathology Portland, OR, USA Mayo Clinic and Mayo Foundation Rochester, MN, USA Shivanand R.Patil, PhD Department of Pediatrics Rhett P.Ketterling, MD University of Iowa College of Division of Laboratory Genetics Medicine Department of Laboratory Iowa City, IA, USA Medicine and Pathology Mayo Clinic and Mayo Willmar Patino, PhD Foundation Wilson Genetics Laboratory Rochester, MN, USA Department of Obstetrics and Gynecology Roger V.Lebo, PhD George Washington University Department of Pathology Medical Center Children’s Hospital Medical Center Washington, DC, USA of Akron, OH, USA Vijay S.Tonk, PhD Brynn Levy, MSc (Med), PhD Departments of Pediatrics and Departments of Human Genetics Pathology and Pediatrics Texas Tech University Health Mount Sinai School of Medicine Sciences Center New York, NY, USA Lubbock, TX, USA R.Ellen Magenis, MD Gopalrao V.N.Velagaleti, PhD Department of Molecular and Departments of Pediatrics and Medical Genetics and Child Pathology xi AUTHORS University of Texas Medical Branch Herman E.Wyandt, PhD Galveston, TX, USA Center for Human Genetics Boston University School of Peter E.Warburton, PhD Medicine Department of Human Genetics Boston, MA, USA Mount Sinai School of Medicine New York, NY, USA xii Foreword Critical to the accurate diagnosis of human illness is the need to distinguish clinical features that fall within the normal range from those that do not. That distinction is often challenging and not infrequently requires considerable experience at the bedside. It is not surprising that accurate cytogenetic diagnosis is also often a challenge, especially when chromosome study reveals morphologic findings that raise the question of normality. Given the realization that modern human cytogenetics is just over five decades old,it is noteworthy that thorough documentation of normal chromosome varia- tion has not yet been accomplished. One key diagnostic consequence of the inability to distinguish a “normal” variation in chromosome structure from a pathologic change is a missed or inaccurate diagnosis. Clinical cytogeneticists have not, however, been idle. Rather, progressive biotechnological advances coupled with virtual completion of the human genome project have yielded increasingly better microscopic resolution of chromosome structure. Witness the progress from the early short condensed chromosomes to the later visualization of chromosomes through banding techniques, high- resolution analysis in prophase, and more recently to analysis by fluorescent in situ hybridization (FISH). Pari passuwith these advances has been the recognition of normal variation in chromosome morphology with each progressive step in microscopic resolu- tion. Most recently, the advent of analysis by FISH aimed at determination of specific subtelomeric deletions revealed that about 5% of individuals with “idiopathic” mental retardation are accounted for by these submicroscopic telomeric rearrangements. An emerging salutary lesson is that some of the sub- telomeric deletions have been observed in entirely normal subjects, and a number of benign familial variants have been documented. Moreover, we now know that demonstration of a subtelomeric deletion in an individual with unex- plained mental retardation should nevertheless be followed by the same studies in both parents, before any diagnostic conclusion or phenotypic association is reached. Whether or not observed microdeletions in normal subjects reflect population variation or are not associated with a particular phenotype simply because of gene dosage effects (e.g., trisomy or monosomy) remain unknown. While telomeric imbalances that are not pathogenic have been described (including from 10q and 17p), a full appreciation, size assessment and catego- rization, is yet to be accomplished. Careful adherence to strict epidemiologic xiii