ISCN 2013 An International System for Human Cytogenetic Nomenclature (2013) Editors Lisa G. Shaffer Jean McGowan-Jordan Michael Schmid Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature This report should be cited in text as ISCN (2013). The complete citation for reference lists is: ISCN (2013): An International System for Human Cytogenetic Nomenclature, L.G. Shaffer, J. McGowan-Jordan, M. Schmid (eds); S. Karger, Basel 2013 Published in collaboration with
Published in collaboration with Cytogenetic and Genome Research under the title ISCN 2013: An International System for Human Cytogenetic Nomenclature (2013) VI + 140 p. plus fold-out, 11 fig., 4 tab., 2013 Although produced by the editors and publishers of Cytogenetic and Genome Research, this publication is independent of the subscription. Copies of ISCN 2013 can be ordered from the publishers: S. Karger AG S. Karger Publishers, Inc. Allschwilerstrasse 10 26 West Avon Road P.O. Box P.O. Box 529 CH 4009 Basel Unionville, CT 06085 Switzerland Tel. (860) 675-7834 Tel. +41 61 306 11 11 Fax (860) 675-7302 Fax +41 61 306 12 34 Toll free: 1-800-828-5479 E-Mail karger@karger.ch Library of Congress Cataloging-in-Publication Data International Standing Committee on Human Cytogenetic Nomenclature. ISCN 2013 : an international system for human cytogenetic nomenclature (2013) / editors, Lisa G. Shaffer, Jean McGowan-Jordan, Michael Schmid. p. ; cm. International system for human cytogenetic nomenclature (2013) Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature. Published in collaboration with Cytogenetic and Genome Research. Includes bibliographical references and index. ISBN 978-3-318-02253-7 (soft cover : alk. paper) I. Shaffer, Lisa G. II. McGowan-Jordan, Jean. III. Schmid, M. (Michael) IV. Cytogenetic and genome research. V. Title. VI. Title: International system for human cytogenetic nomenclature (2013). [DNLM: 1. Cytogenetics--Terminology--English. QU 15] 611.01816--dc23 2012034067 Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. S. Karger Medical and Scientific Publishers Basel Freiburg Paris London New York Bangalore Bangkok Shanghai Singapore Tokyo Sydney All rights reserved. No part of this publication may be translated into other languages, reproduced, or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Copyright 2013 by S. Karger AG, P.O. Box, CH 4009 Basel (Switzerland) Printed in Switzerland by Reinhardt Druck, Basel ISBN 978 3 318 02253 7
Table of Contents 1 Historical Introduction... 1 1.1 1956 1984... 1 1.2 1985 1995... 3 1.3 1996 2004... 4 1.4 2005 2009... 5 1.5 2010 2013... 5 2 Normal Chromosomes... 6 2.1 Introduction... 6 2.2 Chromosome Number and Morphology... 6 2.2.1 Non-Banding Techniques... 6 2.2.2 Banding Techniques... 7 2.2.3 X- and Y-Chromatin... 8 2.3 Chromosome Band Nomenclature... 9 2.3.1 Identification and Definition of Chromosome Landmarks, Regions, and Bands.. 9 2.3.2 Designation of Regions, Bands, and Sub-Bands... 10 2.4 High-Resolution Banding... 12 2.5 Molecular Basis of Banding... 15 3 Symbols and Abbreviated Terms... 36 4 Karyotype Designation... 39 4.1 General Principles... 39 4.2 Specification of Breakpoints... 41 4.3 Designating Structural Chromosome Aberrations by Breakpoints and Band Composition... 42 4.3.1 Short System for Designating Structural Chromosome Aberrations... 42 4.3.1.1 Two-Break Rearrangements... 42 4.3.1.2 Three-Break Rearrangements... 43 4.3.1.3 Four-Break and More Complex Rearrangements... 44 4.3.2 Detailed System for Designating Structural Chromosome Aberrations... 44 4.3.2.1 Additional Symbols... 44 4.3.2.2 Designating the Band Composition of a Chromosome... 45 4.4 Derivative Chromosomes... 45 4.5 Recombinant Chromosomes... 46
5 Uncertainty in Chromosome or Band Designation... 49 5.1 Questionable Identification... 49 5.2 Uncertain Breakpoint Localization or Chromosome Number... 50 5.3 Alternative Interpretation... 50 5.4 Incomplete Karyotype... 51 6 Order of Chromosome Abnormalities in the Karyotype... 52 7 Normal Variable Chromosome Features... 53 7.1 Variation in Heterochromatic Segments, Satellite Stalks, and Satellites... 53 7.1.1 Variation in Length... 53 7.1.2 Variation in Number and Position... 53 7.2 Fragile Sites... 54 8 Numerical Chromosome Abnormalities... 55 8.1 General Principles... 55 8.2 Sex Chromosome Abnormalities... 56 8.3 Autosomal Abnormalities... 57 8.4 Uniparental Disomy... 58 9 Structural Chromosome Rearrangements... 59 9.1 General Principles... 59 9.2 Specification of Structural Rearrangements... 60 9.2.1 Additional Material of Unknown Origin... 60 9.2.2 Deletions... 61 9.2.3 Derivative Chromosomes... 62 9.2.4 Dicentric Chromosomes... 67 9.2.5 Duplications... 69 9.2.6 Fission... 69 9.2.7 Fragile Sites... 69 9.2.8 Homogeneously Staining Regions... 70 9.2.9 Insertions... 71 9.2.10 Inversions... 72 9.2.11 Isochromosomes... 72 9.2.12 Marker Chromosomes... 73 9.2.13 Neocentromeres... 75 9.2.14 Quadruplications... 75 9.2.15 Ring Chromosomes... 75 9.2.16 Telomeric Associations... 77 9.2.17 Translocations... 78 9.2.17.1 Reciprocal Translocations... 78 9.2.17.2 Whole-Arm Translocations... 80 9.2.17.3 Robertsonian Translocations... 81 9.2.17.4 Jumping Translocations... 82 9.2.18 Tricentric Chromosomes... 83 9.2.19 Triplications... 83 9.3 Multiple Copies of Rearranged Chromosomes... 83 IV ISCN 2013
10 Chromosome Breakage... 85 10.1 Chromatid Aberrations... 85 10.1.1 Non-Banded Preparations... 85 10.1.2 Banded Preparations... 86 10.2 Chromosome Aberrations... 86 10.2.1 Non-Banded Preparations... 86 10.2.2 Banded Preparations... 87 10.3 Scoring of Aberrations... 87 11 Neoplasia... 88 11.1 Clones and Clonal Evolution... 88 11.1.1 Definition of a Clone... 88 11.1.2 Clone Size... 89 11.1.3 Mainline... 89 11.1.4 Stemline, Sideline and Clonal Evolution... 90 11.1.5 Composite Karyotype... 92 11.1.6 Unrelated Clones... 94 11.2 Modal Number... 94 11.3 Constitutional Karyotype... 95 12 Meiotic Chromosomes... 97 12.1 Terminology... 97 12.1.1 Examples of Meiotic Nomenclature... 98 12.1.2 Correlation between Meiotic Chromosomes and Mitotic Banding Patterns... 100 13 In situ Hybridization... 105 13.1 Introduction... 105 13.2 Prophase/Metaphase in situ Hybridization (ish)... 105 13.2.1 Use of dim and enh... 111 13.2.2 Subtelomeric Metaphase in situ Hybridization... 111 13.3 Interphase/Nuclear in situ Hybridization (nuc ish)... 111 13.3.1 Number of Signals... 112 13.3.2 Relative Position of Signals... 115 13.3.2.1 Single Fusion Probes... 117 13.3.2.2 Single Fusion with Extra Signal Probes... 117 13.3.2.3 Dual Fusion Probes... 117 13.3.2.4 Break-Apart Probes... 118 13.4 In situ Hybridization on Extended Chromatin/DNA Fibers (fib ish)... 119 13.5 Reverse in situ Hybridization (rev ish)... 119 13.5.1 Chromosome Analyses Using Probes Derived from Sorted or Microdissected Chromosomes... 119 13.6 Chromosome Comparative Genomic Hybridization (cgh)... 120 13.7 Multi-Color Chromosome Painting... 120 13.8 Partial Chromosome Paints... 120 Table of Contents V
14 Microarrays... 121 14.1 Introduction... 121 14.2 Examples of Microarray Nomenclature... 122 14.2.1 Nomenclature Specific to SNP Arrays... 127 14.2.2 Complex Array Results... 128 15 Region-Specific Assays... 129 15.1 Introduction... 129 15.2 Examples of RSA Nomenclature for Copy Number Detection... 129 15.3 Examples of RSA Nomenclature for Balanced Translocations or Fusion Genes... 130 16 References... 131 17 Members of the ISCN Standing Committee and Consultants... 133 18 Appendix... 135 19 Index... 137 VI ISCN 2013