Table Of ContentEeva Therman
Human
Chromosomes
Structure, Behavior, Effects
With 55 Figures
Springer-Verlag
New York Heidelberg Berlin
EEYA THERMAN
Department of Medical Genetics, University of Wiscon
sin, Madison, Wisconsin 53706, USA
Library of Congress Cataloging in Publication Data
Therman, Eeva.
Human chromosomes.
Includes bibliographies.
1. Human genetics. 2. Human chromosomes.
3. Human chromosome abnormalities. I. Title.
[DNLM: 1. Chromosomes, Human. QH600 T41lh]
QH431.T436 611'.01816 80-21278
All rights reserved.
No part of this book may be translated or reproduced in any
form without written permission from Springer-Verlag.
The use of general descriptive names, trade names, trademarks,
etc. in this publication, even if the former are not especially
identified, is not to be taken as a sign that such names, as
understood by the Trade Marks and Merchandise Marks Act,
may accordingly be used freely by anyone.
© 1980 by Springer-Verlag New York Inc.
Softcover reprint of the hardcover 1s t edition 1980
9 8 7 6 5 4 3 2 1
ISBN-13: 978-1-4684-0109-7 e-ISBN-13: 978-1-4684-0107-3
DOl: 10.1007/978-1-4684-0107-3
For KLAUS PATAU
Preface
This book provides an introduction to human cytogenetics. It is also
suitable for use as a text in a general cytogenetics course, since the basic
features of chromosome structure and behavior are shared by all eukar
yotes. Because my own background includes plant and animal cytoge
netics, many of the examples are taken from organisms other than man.
Since the book is written from a cytogeneticist's point of view, human
syndromes are described only as illustrations of the effects of abnormal
chromosome constitutions on the phenotype. The selection of the phe
nomena to be discussed and of the photographs to illustrate them is, in
many cases, subjective and arbitrary and is naturally influenced by my
interests and the work done in our laboratory.
The approach to citations is the exact opposite of that usually used in
scientific papers. Whenever possible, the latest and/or most comprehen
sive review has been cited, instead of the original publication. Thus the
reader is encouraged to delve deeper into any question of interest to him
or her.
I am greatly indebted to many colleagues for suggestions and criticism.
However, my special thanks are due to Dr. JAMES F. CROW, Dr. TRAUTE
M. SCHROEDER, and Dr. CARTER DENNISTON for their courage in reading
the entire manuscript. I wish to express my gratitude also to the
cytogeneticists and editors who have generously permitted the use of
published and unpublished photographs.
Members of my laboratory have been very helpful in the process of
putting this book together. Mrs. BARBARA SUSMAN has been involved in
all the phases, from compiling reference lists to designing illustrations.
viii Preface
The photographic work has been done by Mr. WALTER KUGLER, Jr.;
our excellent secretary, Ms. CHRISTINE ONAGA, has cheerfully typed
and retyped the manuscript.
However, my most special thanks I wish to reserve for the editor of
this book, Ms. MARY Lou MOTL. When my Finnish-English emerges
from her competent hands, it resembles the text I would have liked to
have written in the first place.
Madison, Wisconsin EEVA THERMAN
September, 1980
Contents
I. Past and Future of Human Cytogenetics
The Past of Human Cytogenetics ........................... 1
Human Sex Chromosomes ................................ .4
Evolution of Human Chromosomes ........................ .4
Nomenclature of Human Chromosomes ..................... 5
The Future of Human Cytogenetics ......................... 5
Structure of the Eukaryotic Chromosome ................... 6
Mapping of Human Chromosomes ..........................7
Chromosomes and Cancer .................................7
Mutagenesis Studies ......................................7
Cytology of Development .................................8
Clinical Cytogenetics ..................................... 8
References ............................................... 9
II. Structure of the Eukaryotic Chromosome and the Karyotype
Metaphase Chromosome ................................. 11
Chromosome Number .................................... 15
Chromosome Size ....................................... 15
Shape of Chromosomes .................................. 16
DNA Content of Nuclei .................................. 17
Human Chromosome Complement ........................ 17
Banded Human Karyotype ............................... 19
Euploid Chromosome Changes ............................ 21
Aneuploid Chromosome Changes ......................... 22
Structural Changes in Chromosomes .......................2 2
References .............................................. 23
x Contents
III. Mitotic Cycle and Chromosome Reproduction
Significance of Mitosis ................................... 24
Nondisjunction and Loss of Chromosomes .................2 6
Mitotic Cycle ...........................................2 7
Chromosome Replication .................................2 8
References ..............................................2 9
IV. Modifications of Mitosis
Endoreduplication .............................. " ....... 30
Endomitosis ............................................ 32
Polytene Chromosomes ..................................3 3
C-Mitosis ............................................... 34
Restitution .............................................. 34
Multipolar Mitoses ......................................3 4
Methods of Studying Endopolyploidy ...................... 34
Somatic Polyploidy and Differentiation .....................3 5
The Role of Somatic Polyploidy in Differentiation ...........3 6
References .............................................. 37
V. Methods in Human CytogenetiCS
Direct Methods ......................................... 39
Tissue-Culture Techniques ............................... 040
Meiotic Studies ........................................ Al
Sex Chromatin Techniques .............................. Al
Autoradiography ....................................... Al
Banding Techniques on Fixed Chromosomes .............. 042
Banding Techniques for Cells in Culture .................. 045
Nomenclature of Human Chromosomes ................... 045
References ..............................................4 7
VI. Longitudinal Differentiation of Eukaryotic Chromosomes
Prebanding Studies ...................................... 50
Banding Studies on Human Chromosomes .................5 1
Constitutive Heterochromatin ............................. 53
Facultative Heterochromatin .............................. 56
Intercalary Heterochromatin .............................. 56
Chromosome Bands ..................................... 57
Function of Human Chromosome Bands ...................5 8
References .............................................. 59
VII. Chromosome Structural Aberrations
Origin of Structurally Abnormal Chromosomes .............6 1
Contents xi
Chromosome Breaks and Rearrangements ..................6 2
Chromatid Breaks and Rearrangements ....................6 4
Telomeres ..............................................6 5
Triradial and Multiradial Chromosomes ....................6 6
Centric Fusion ..........................................6 7
Inactivation of the Centromere ............................6 8
Misdivision .............................................6 9
Interphase-like Chromosomes in Metaphase ................6 9
Sister Chromatid Exchanges ..............................7 0
References ..............................................7 0
VIII. Causes of Chromosome Breaks
Spontaneous Chromosome Breaks .........................7 3
Points of Weakness in Human Chromosomes ...............7 4
Radiation-Induced Breaks ................................7 4
Chemically Induced Breaks ...............................7 5
Virus-Induced Breaks ....................................7 7
Genetic Causes of Chromosome Breakage ..................7 7
Nonrandomness of Chromosome Breaks ...................7 8
Methods in Chromosome-Breakage Studies .................7 9
References .............................................. 80
IX. The Main Features of Meiosis
Significance of Meiosis ...................................8 3
Meiotic Stages ..........................................8 4
Premeiotic Interphase ....................................8 4
Leptotene (or Leptonema) ................................8 6
Zygotene (or Zygonema) .................................8 6
Pachytene (or Pachynema) ................................ 86
Diplotene (or Diplonema) .................................8 9
Diakinesis ..............................................9 0
Metaphase I ............................................9 0
Anaphase I ............................................. 90
Telophase I .............................................9 1
Interkinesis .............................................9 1
Meiotic Division II ......................................9 2
References ..............................................9 3
X. Details of Meiosis
Structure of Chiasmata ...................................9 4
Number of Chiasmata ....................................9 4
Synaptonemal Complex ..................................9 6
xii Contents
Meiotic Behavior of More Than Two Homologous
Chromosomes .........................................9 7
Human Meiosis .........................................9 9
Premeiotic and Early Meiotic Stages in Man ................9 9
Human Meiotic Stages from Diplotene on .......... " ..... 101
Behavior of X and Y Chromosomes ...................... 101
References ............................................. 102
XI. Meiotic Abnormalities
Nondisjunction of Autosomes ............................ 104
Nondisjunction of Sex Chromosomes ..................... 105
Misdivision of the Centromere ........................... 106
Environmental Causes of Meiotic Nondisjunction .......... 106
Maternal Age .......................................... 108
Genetic Causes of Nondisjunction ........................ 109
Origin of Diploid Gametes ............................... 110
References ............................................. 110
XII. Human Sex Chromosomes
The Y Chromosome .................................... 112
Sex Determination in Man ............................... 113
H-Y Antigen ........................................... 114
Genes on the Y Chromosome ............................ 115
Abnormal Y Chromosomes .............................. 115
The X Chromosome .................................... 115
X Chromatin or Barr Body Formation .................... 116
Inactivation of the X Chromosome ....................... 118
Behavior of X and Y Chromosomes in Meiocytes .......... 121
Sex Reversal Genes .................................... 121
References ............................................. 122
XIII. Sex Chromosome Abnormalities
Aneuploidy of X Chromosomes in Individuals with a
Female Phenotype .................................... 125
Sex Chromosome Aneuploidy with a Male
Phenotype ........................................... 128
Mosaicism ............................................. 129
Abnormal X Chromosomes Consisting of X Material ....... 130
X Inactivation Center ................................... 132
X-Autosomal Translocations ............................. 132
Translocations Involving the Y Chromosome .............. 133
Abnormal X Chromosome Constitutions and the
Phenotype ........................................... 133
References ............................................. 134
