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An International System for Human Cytogenetic Nomenclature (2013) Editors Lisa G. Shaffer Shaffer Jean McGowan-Jordan Michael Schmid Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature
This report should be cited cited in text as ISCN (201 (2013). 3). The complete citation citation for reference reference lists is: is: ISCN (2013): An Internationa Internationall System System for Human Cytogenetic Cytogenetic Nomenclatu Nomenclature, re, 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 Allschwilerstrasse 10 P.O. Box CH–4009 Basel Switzerland Tel. +41 61 306 11 11 Fax +41 61 306 12 34 E-Mail
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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
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ISBN 978–3–318–02253–7
Table of Contents
1 1.1 1.2 1.3 1.4 1.5
Historical Introduction...................... ....................... ........................
2 2.1 2.2 2.2.1 2.2.2 2.2.3 2.3 2.3.1 2.3.2 2.4 2.5
Normal Chromosomes ..................................................................... Introduction..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... . Chromosome Number and Morphology.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . Non-Banding Techniques ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... Banding Techniques ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... X- and Y-Chromatin ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... . Chromosome Band Nomenclature ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... Identification and Definition of Chromosome Landmarks, Regions, and Bands .. Designation of Regions, Bands, and Sub-Bands .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . High-Resolution Banding ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... Molecular Basis of Banding ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .
6 6 6 6 7 8 9 9 10 12 15
3
Symbols and Abbreviated Terms ....................................................
36
4 4.1 4.2 4.3
Karyotype Designation ....................................................................
39 39 41
4.3.1 4.3.1.1 4.3.1.2 4.3.1.3 4.3.2 4.3.2.1 4.3.2.2 4.4 4.5
1956–1984 ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ... 1985–1995 ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ... 1996–2004 ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ... 2005–2009 ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ... 2010–2013 ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ...
General Principles .... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ... Specification of Breakpoints ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... Designating Structural Chromosome Aberrations by Breakpoints and Band Composition ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... . Short System for Designating Structural Chromosome Aberrations . .. .. .. .. .. .. .. .. Two-Break Rearrangements ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... Three-Break Rearrangements ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . Four-Break and More Complex Rearrangements .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. Detailed System for Designating Structural Chromosome Aberrations. .... .... .... Additional Symbols ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. Designating the Band Composition of a Chromosome .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. Derivative Chromosomes ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... Recombinant Chromosomes... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ..
1 1 3 4 5 5
42 42 42 43 44 44 44 45 45 46
5 5.1 5.2 5.3 5.4
Uncertainty in Chromosome or Band Designation ........................ Questionable Identification ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... Uncertain Breakpoint Localization or Chromosome Number.. . .. . .. .. .. .. .. .. .. .. .. .. Alternative Interpretation... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... Incomplete Karyotype ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .
49 49 50 50 51
6
Order of Chromosome Abnormalities in the Karyotype ................
52
7 7.1 7.1.1 7.1.2 7.2
Normal Variable Chromosome Features..................... ....................
53 53 53 53 54
8 8.1 8.2 8.3 8.4
Numerical Chromosome Abnormalities...................... ....................
Variation in Heterochromatic Segments, Satellite Stalks, and Satellites .... .... .... Variation in Length ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... . Variation in Number and Position ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . Fragile Sites ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... .
General Principles .... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ... Sex Chromosome Abnormalities ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... Autosomal Abnormalities ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... Uniparental Disomy..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .
55 55 56 57 58
Structural Chromosome Rearrangements ...................... ................ 9 9.1 General Principles .... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ... 9.2 Specification of Structural Rearrangements .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 9.2.1 Additional Material of Unknown Origin .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 9.2.2 Deletions ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... . 9.2.3 Derivative Chromosomes ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 9.2.4 Dicentric Chromosomes ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 9.2.5 Duplications ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... 9.2.6 Fission ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ... 9.2.7 Fragile Sites ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... . 9.2.8 Homogeneously Staining Regions ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 9.2.9 Insertions ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ... 9.2.10 Inversions ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ... 9.2.11 Isochromosomes ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ... 9.2.12 Marker Chromosomes..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .. 9.2.13 Neocentromeres ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... 9.2.14 Quadruplications ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... .... 9.2.15 Ring Chromosomes ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... . 9.2.16 Telomeric Associations ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 9.2.17 Translocations ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ... 9.2.17.1 Reciprocal Translocations ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 9.2.17.2 Whole-Arm Translocations....................................................................... 9.2.17.3 Robertsonian Translocations ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 9.2.17.4 Jumping Translocations ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 9.2.18 Tricentric Chromosomes ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 9.2.19 Triplications ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... . 9.3 Multiple Copies of Rearranged Chromosomes .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .
59 59 60 60 61 62 67 69 69 69 70 71 72 72 73 75 75 75 77 78 78 80 81 82 83 83 83
IV
ISCN 2013
10 10.1 10.1.1 10.1.2 10.2 10.2.1 10.2.2 10.3
Chromosome Breakage....................................................................
11 11.1 11.1.1 11.1.2 11.1.3 11.1.4 11.1.5 11.1.6 11.2 11.3
Neoplasia ..........................................................................................
12 12.1 12.1.1 12.1.2
Meiotic Chromosomes .....................................................................
13 13.1 13.2 13.2.1 13.2.2 13.3 13.3.1 13.3.2 13.3.2.1 13.3.2.2 13.3.2.3 13.3.2.4 13.4 13.5 13.5.1
In situ Hybridization ........................................................................
13.6 13.7 13.8
Chromatid Aberrations ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... Non-Banded Preparations ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. Banded Preparations ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... Chromosome Aberrations ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. Non-Banded Preparations ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. Banded Preparations ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... Scoring of Aberrations ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .
Clones and Clonal Evolution ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. Definition of a Clone ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... Clone Size ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ... Mainline ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... . Stemline, Sideline and Clonal Evolution .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . Composite Karyotype ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. Unrelated Clones ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ... Modal Number .... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ... Constitutional Karyotype ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .
Terminology ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... . Examples of Meiotic Nomenclature ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. Correlation between Meiotic Chromosomes and Mitotic Banding Patterns ... ....
85 85 85 86 86 86 87 87 88 88 88 89 89 90 92 94 94 95 97 97 98 100
105 Introduction..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... . 105 Prophase/Metaphase in situ Hybridization (ish) .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 105 Use of dim and enh ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... . 111 Subtelomeric Metaphase in situ Hybridization .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 111 Interphase/Nuclear in situ Hybridization (nuc ish) .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 111 Number of Signals.................................................................................. 112 Relative Position of Signals ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 115 Single Fusion Probes ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 117 Single Fusion with Extra Signal Probes .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 117 Dual Fusion Probes ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 117 Break-Apart Probes ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 118 In situ Hybridization on Extended Chromatin/DNA Fibers (fib ish) .. . .. .. .. .. .. .. .. .. 119 Reverse in situ Hybridization (rev ish) .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 119 Chromosome Analyses Using Probes Derived from Sorted or Microdissected Chromosomes ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... ..... ... 119 Chromosome Comparative Genomic Hybridization (cgh) .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 120 Multi-Color Chromosome Painting ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 120 Partial Chromosome Paints ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 120
Table of Contents
V
14 14.1 14.2 14.2.1 14.2.2
Microarrays .......................................................................................
15 15.1 15.2 15.3
Region-Specific Assays...................... ....................... ........................ Introduction..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... . Examples of RSA Nomenclature for Copy Number Detection .. .. . .. .. .. .. .. .. .. .. .. .. Examples of RSA Nomenclature for Balanced Translocations or Fusion Genes ...
129 129 129 130
16
References ........................................................................................
131
17
Members of the ISCN Standing Committee and Consultants ........
133
18
Appendix ..........................................................................................
135
19
Index .................................................................................................
137
Introduction..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... ..... .... . Examples of Microarray Nomenclature.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . Nomenclature Specific to SNP Arrays.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . Complex Array Results ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .
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