Eeva Therman. Human Chromosomes. Structure, Behavior, Effects. Second Edition. With 87 Figures. Springer-Verlag New York Berlin Heidelberg Tokyo

Transcription

1 Human Chromosomes

2 Eeva Therman Human Chromosomes Structure, Behavior, Effects Second Edition With 87 Figures Springer-Verlag New York Berlin Heidelberg Tokyo

3 Eeva Therman Laboratory of Genetics University of Wisconsin Madison, WI U.S.A. Library of Congress Cataloging-in-Publication Data Therman, Eeva. Human chromosomes. Includes bibliographies and indexes. 1. Human chromosomes. 2. Human cytogenetics. 3. Human chromosome abnormalities. I. Title. [DNLM: 1. Chromosomes, Human. 2. Cytogenetics. QH 600 T411h] QH431.T ' , 1986 by Springer-Verlag New York Inc. All rights reserved. No part of this book may be translated or reproduced in any form without written permission from Springer-Verlag, 175 Fifth Avenue, New York, New York 10010, U.S.A. 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. While the advice and information of this book is believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to material contained herein. Media conversion by University Graphics Inc., Atlantic Highlands, New Jersey ISBN-13: ()..387-% : / e-isbn-13:

4 For Klaus Palau

5 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 eukaryotes. Because my own background includes plant and animal cytogenetics, many of the examples are taken from organisms other than the human. 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 phenomena 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 above paragraph from the Preface of the first edition of this book also fits the present edition. However, so much has happened in five years in cytogenetics that-apart from a couple of pages here and there-the whole book has been rewritten and nine new chapters have been added. The system used in the first edition to cite, whenever possible, the latest and/or the most comprehensive review rather than the original publications has been followed here also. Not only would complete literature citations increase the size of the book too much, but many readers have expressed satisfaction with the referencing method used here. For suggestions and criticism I am greatly indebted to many colleagues, of whom I would especially like to mention Drs. Evelyn M. Kuhn, Richard Spritz, Millard Susman, and Bernard Weisblum. Furthermore, I appreciate the heroism of Drs. James F. Crow and Carter Denniston for reading and annotating the whole manuscript. I am grateful to the cytogeneticists and editors who have generously permitted the use of published and unpublished pictures. I wish to Vll

6 Vlll Preface express my special thanks to Dr. Carolyn Trunca for allowing me to use her unpublished analysis of the segregation of human translocations, and to Dr. Andrew Drewry for giving me unpublished data. Without the help of members of my laboratory, Mrs. Barbara Susman and Mr. Walter Kugler, Jr., this book would hardly exist. Mrs. Susman has been involved in all phases from compiling literature lists to designing illustrations, and Mr. Kugler has done all the photographic work. My sincere thanks are due to our secretaries, Ms. Juli-Kay Baumann and Mrs. Sandy Keller, who have typed and retyped the manuscript. I wish to express my special gratitude to Dr. Ilse Riegel, whose help has been invaluable. Madison, Wisconsin November Eeva Therman

7 Contents I. Past and Future of Human Cytogenetics.... The Past of Human Cytogenetics I The Dark Ages The Hypotonic Era... 2 The Trisomy Period Chromosome Banding Era... 3 Human Sex Chromosomes Evolution of Human Chromosomes Nomenclature of Human Chromosomes The Future of Human Cytogenetics Ultrastructure of Eukaryotic Chromosomes... 6 Longitudinal Differentiation of Chromosomes Structure ofinterphase Nuclei... 7 Sex Determination and Sex Chromosomes Mapping of Human Chromosomes... 8 Chromosomes and Cancer Somatic Cell Cytogenetics Mutagenesis Studies Chromosome Breakage Syndromes... 9 Clinical Cytogenetics References II. Structure of the Eukaryotic Chromosome and the Karyotype 13 Metaphase Chromosome Primary Constriction Secondary Constrictions Characterization of Metaphase Chromosomes Chromosome Number Chromosome Size Shape of Chromosomes IX

8 x Contents DNA Content of Nuclei Human Chromosome Complement Banded Human Karyotype Euploid Chromosome Changes Aneuploid Chromosome Changes Structural Changes in Chromosomes References III. Mitotic Cycle and Chromosome Reproduction Significance of Mitosis Interphase Prophase... o. 27 Prometaphase Metaphase Anaphase Telophase Chromosome Arrangement Nondisjunction and Loss of Chromosomes Mitotic Cycle Chromosome Replication References IV. Methods of Human Cytogenetics Direct Methods Tissue Culture Techniques Prenatal Studies Meiotic Studies Sex Chromatin Techniques Autoradiography Banding Techniques of Fixed Chromosomes Banding Techniques for Cells in Culture Prophase Banding Nomenclature of Human Chromosomes Quantitative Methods References V. Longitudinal Differentiation of Eukaryotic Chromosomes Longitudinal Differentiation of Chromosomes Molecular Differentiation of Chromosomes Prebanding Studies Banding Studies on Human Chromosomes Nucleoli and Chromocenters Constitutive Heterochromatin Facultative Heterochromatin Intercalary Heterochromatin Chromosome Bands Function of Human Chromosome Bands References

9 Contents Xl VI. Fine Structure and Function of the Eukaryotic Chromosome 58 Chromosome Fine Structure Polytene and Lampbrush Chromosomes References VII. Chromosome Structural Aberrations Origin of Structurally Abnormal Chromosomes Chromosome Breaks and Rearrangements Chromatid Breaks and Rearrangements Telomeres Telomere Association The Origin of Dicentric Chromosomes Including Isodicentrics and Isochromosomes Inactivation of the Centromere Misdivision Centric Fusion Triradial and Multiradial Chromosomes Fragile Regions References VIII. Causes of Chromosome Breaks Spontaneous Chromosome Breaks Radiation-Induced Breaks Chemically Induced Breaks Virus-Induced Breaks Genetic Causes of Chromosome Breaks Nonrandomness of Chromosome Breaks Methods in Chromosome-Breakage Studies Rules for Chromosome-Breakage Studies References IX. Chromosome Breakage Syndromes Genotypic Chromosome Breakage Bloom's Syndrome Fanconi's Anemia Ataxia Telangiectasia Other Conditions with Increased Chromosome Aberrations Cancer and Chromosome-Breakage Syndromes References X. Sister Chromatid Exchanges and Mitotic Crossing-Over The Detection of Sister Chromatid Exchanges The Occurrence of SCE SCE in Mutagenesis Research..., Significance of SCE Mitotic Crossing-Over

10 xii Contents Nonrandom Localization of Chiasmata Segregation after Mitotic Recombination The Origin of Mitotic Chiasmata Gene Amplification References XI. Cell Fusion, Prematurely Condensed Chromosomes, and the Origin of Allocyclic Chromosomes Cell Fusion Prematurely Condensed Chromosomes (PCC) Uses ofpcc Formation Origin of Allocyclic Chromosomes References XII. Modifications of Mitosis Endoreduplication Polyteny Endomitosis C-Mitosis Restitution Multipolar Mitoses References XIII. Somatic Cell Cytogenetics History of Somatic Cell Cytogenetics Methods of Somatic Cell Cytogenetics Somatic Polyploidy Structure of Nuclei in Somatic Cells Amplification and Underreplication Somatic Cell Cytogenetics and Differentiation References XIV. Main Features of Meiosis Significance of Meiosis Meiotic Stages Premeiotic Interphase Leptotene (or Leptonema) Zygotene (or Zygonema) Pachytene (or Pachynema) Diplotene (or Diplonema) Diakinesis Metaphase I Anaphase I Telophase I Interkinesis Meiotic Division II

11 Contents xiii Some Meiotic Features References xv. Details of Meiosis Structure of Chiasmata Number of Chiasmata Synaptonemal Complex Meiotic Behavior of More Than Two Homologous Chromosomes Human Meiosis Premeiotic and Early Meiotic Stages in Man Meiosis in Human Spermatocytes Behavior of X and Y Chromosomes References XVI. Meiotic Abnormalities Nondisjunction of Autosomes Nondisjunction of Sex Chromosomes Misdivision of the Centromere Chromosomally Abnormal Human Sperm Male Infertility Environmental Causes of Meiotic Nondisjunction Maternal Age Genetic Causes of Nondisjunction Origin of Diploid Gametes References XVII. Human Sex Determination and the Y Chromosome The Y Chromosome Sex Determination in Man H-Y Antigen Genes on the Y Chromosome Abnormal Y Chromosomes References XVIII. Human X Chromosome The Structure of the X Chromosome X Chromatin or Barr Body Formation Inactivation of the X Chromosome Reactivation of the X Chromosome Sex Reversal and Intersexuality References XIX. Numerical Sex Chromosome Abnormalities Aneuploidy of X Chromosomes in Individuals with a Female Phenotype

12 XIV Contents Sex Chromosome Aneuploidy with Male Phenotype Mosaicism References XX. Structurally Abnormal X Chromosomes Abnormal X Chromosomes Consisting of X Material X Inactivation Center X;Autosome Translocations and the Critical Region Always-Active Regions on the Inactive X Chromosome Translocations Involving the Y Chromosome Abnormal X Chromosome Constitutions and the Female Phenotype Various Behavioral Abnormalities of the X Chromosome Summary of Mammalian X Inactivation References XXI. Numerically Abnormal Chromosome Constitutions in Humans Abnormalities of Human Chromosome Number Polyploidy Human Triploids Hydatidiform Moles Human Tetraploids Autosomal Aneuploidy Anomalies Caused by Chromosomal Imbalance Trisomy (DJ Trisomy, Patau's Syndrome) Trisomy Syndrome (Down's Syndrome, Mongolism) Trisomy Syndrome (Edward's Syndrome) Other Autosomal Aneuploidy Syndromes Spontaneous Abortions References XXII. Structurally Abnormal Human Autosomes Structurally Abnormal Chromosomes Chromosomal Polymorphisms Quantitative Comparisons Pericentric Inversions Paracentric Inversions Deletions or Partial Monosomies Cri du Chat (Cat Cry) Syndrome Ring Chromosomes Insertions Duplication or Pure Partial Trisomy Dicentric Chromosomes References XXIII. Reciprocal Translocations Occurrence Breakpoints in Reciprocal Translocations

13 Contents xv Multiple Rearrangements Phenotypes of Balanced Translocation Carriers Phenotypes of Unbalanced Translocation Carriers Fetal Death Examples of Translocation Families Meiosis in Translocation Carriers Genetic Risk for Translocation Carriers References XXIV. Robertsonian Translocations Occurrence Monocentric and Dicentric Chromosomes Relative Frequencies of the Different Types of Robertsonian Translocations Studies on the Newborn Ascertainment Through an Unbalanced Individual Ascertainment Through Infertility Nonrandomness of Robertsonian Translocations Segregation in Carriers of Robertsonian Translocations Interchromosomal Effects References XXV. Double Minutes and Homogeneously Stained Regions What are DMs and HSRs? Structure of Double Minutes Homogeneously Stained Regions and C-Minus Chromosomes DMs and HSRs as Expressions of Gene Amplification DMs and HSRs are Interchangeable Origin of DMs and HSRs Significance of HSRs and DMs References XXVI. Chromosomes and Oncogenes What is Cancer? Cancer Induction Oncogenes Reciprocal Translocations and Oncogenes Recessive Oncogenes Multistep Carcinogenesis References XXVII. Chromosomal Development of Cancer Chromosomes and Cancer Progression Chromosome Studies in Ascites Tumors Chromosome Studies in Primary Tumors The Apparent Predetermination of Chromosome Changes in Cancer Mitotic Aberrations in Cancer Cells Effect of Chromosome Changes on Tumor Development References

14 xvi Contents XXVIII. Mapping of Human Chromosomes Gene Mapping Family Studies Marker Chromosomes Cell Hybridization Selection Chromosome Translocations Other Uses of Deletions and Translocations in Mapping Transfer of Microcells and Single Chromosomes Gene Dosage In-situ Hybridization Recombinant DNA Gene Mapping Methods Conclusions References Author Index Subject Index