Medical Cytogenetics

701 Pages·2000·106.176 MB·English

by  Mark Hon Fong L.

Brown ~niversityS chool of Medicine
Rhode Island ~ e p a ~ ~oef ~neta lth
Providence, and
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my family, without whom all worldly achievementsa re meaningless;
and to the memory my sons, Lancelot and Vincent, who died a rare
genetic disease contractedf rom parents born worlds apart and brought
together by destiny.
This Page Intentionally Left Blank
In this age of electronic communication and rapid advancements in genetic
knowledge and technology, one might wonder about the usefulness of a
textbook in anyf ield of genetics. However,m any of the basic tenets of
genetics have stood the test of time. Understanding and applying of the
newest advances requires a sound appreciation of these basic tenets. This
book, edited by Hon Fong L. Mark, with chapters by recognized experts in
the field, provides a thorough and clear starting point for students new to
cytogenetics. At the same time, it provides complete coverage of the many
current applications of cytogenetics in medicine. These include a variety of
culturing and staining techniques as well as new methods of in situ hybrid-
ization ranging from simple chromosome identification with centromeric cy-
satellite probes to the newest spectral array of the entire karyotype.
The format is well suited to allow the reader to grasp basic concepts.
There are helpful glossaries to ensure clear understanding of the factual
material and a current bibliography for those who want to read the original
sources of the material provided.
It has been within the last few decades that the correct number of
chromosomes in humans has been appreciated, that we have seen that sexual
dimorphism in mammals is caused by dimorphisms of sex chromosomes,
and that chromosomal analysis has been shown to have potential as a pow-
erful tool in molecular understanding of many forms of cancer. With the
advent of the polymerase chain reaction and other powerful tools for the
study of human diseases at the molecular level, some felt that these ad-
vancements signaled the demise of cytogenetics as a major player in the
study of human genetic disorders. Rather, cytogenetics has continued to
advance in technology and knowledge at a pace comparable to molecular
genetics, and the two have become wedded in a marriage in which each
partner is increasingly difficult to identify individually. Medical Cytogenetics
Foreword
E.
Pr eface
While preparing for the certification examination for the American Board of
Medical Genetics in Clinical Cytogenetics a number of years ago, my col-
leagues and I observed that, while there are numerous reference books and
technical texts on cytogenetics, books giving an overview of medical ge-
netics and clinical cytogenetics are at best few and at worst nonexistent.
There is a unique niche for such a text. Thus, this book provides an overview
of the field of cytogenetics in medicine, with an emphasis on the practice
of clinical cytogenetics in a variety of settings, such as a department of
pathology or pediatrics in an academic medical center, a government-spon-
sored laboratory, or a commercial enterprise.
The targeted audience for this book consists of physicians and scien-
tists in training or in practice, medical and advanced undergraduate and
graduate students interested in medical genetics, cytogeneticists studying for
the certifying examination in Clinical Cytogenetics offered every three years
by the American Board of Medical Genetics (ABMG), and board-certified
medical geneticists desiring a review of the field of cytogenetics for recer-
tification* and other purposes. It is for this audience that great pains have
been taken to compile a large number of practice questions following many
chapters, together with answers to these questions in a separate manual. For
the same reason, a glossary has also been compiled for each chapter. It is
hoped that other medical practitioners, such as pathologists, family medicine
physicians, internists, neurologists, occupational medicine physicians, he-
matologists, medical oncologists, pediatricians, endocrinologists, obstetri-
cians and gynecologists, maternal and fetal medicine physicians, urologists,
public health personnel, and other specialists will find this publication to be
a useful reference on cytogenetics as well.
vi
Preface
It is not the goal of this book to be encyclopedic. Rather, we aim to
convey the excitement of this rapidly evolving field in simple and com-
prehensible fashion as possible. We strive to make this intrinsically inter-
esting topic even more interesting by offering bountiful examples and
illustrations.
book contains 20 chapters. The first chapter discusses the disci-
pline of medical genetics and the place of cytogenetics in the bigger scheme
of things. It is only logical that the former President of the American College
of Medical Genetics, Dr. Reed Pyeritz, be invited a co-author. Chapters
2 to 6 provide basic cytogenetic information on the human genome and the
techniques for gathering and interpreting that information. The Tharapels,
co-authors of Chapter 3, were responsible for the organization of the Mem-
phis Conference, which made significant contribution to the clarification
of human cytogenetic nomenclature. Dr. Sandra Wolman is pathologist and
cytogeneticist with many years of experience and is well qualified to write
with me Chapter 4, on culture and harvest techniques. (Sandy also authored
Chapter 15, on breast cancer, which is one of her many areas of expertise.)
Chapter 6 provides thorough introduction to the technique of HSH. Drs.
Blancato and Haddad have extensive research experience using this molec-
ular cytogenetic technique.
Chapter by Dr. Bruce and Dr. Nancy Schneider, discusses the
applications of cytogenetics in medicine. Nancy was formerly Chair of the
College of American Pathologists (CAP)/American College of Medical Ge-
netics (ACMG) Cytogenetics Resource Committee. Bruce was a recent Chair
of the American College of Medical Genetics Program Committee, on which
I also served, and is one of the most respected geneticists in the New En-
gland region.
Following this chapter, more specialized topics in cytogenetics are dis-
cussed. Whereas many chapters in this book deal with important and essen-
tial topics that can be found in other cytogenetics texts, other chapters-
such as those on chromosomal instability and fragile sites, breast cancer,
male infertility and transfusion medicine-are unique. Neither Dr. Allen
Lamb nor Dr. Wayne Miller, co-authors of Chapter 8 on prenatal diagnosis,
needs introduction; both are well known in the cytogenetics community. Dr.
Dorothy Warburton, author of Chapter 9, on the cytogenetics of reproductive
wastage, is recognized authority in the field. Dr. Mark Sigman, my col-
league and friend at Rhode Island Hospital and co-author of Chapter 10, on
the cytogenetics of male infertility, is an expert on this subject. Chapter 11
was written by Drs. John Anastasi and Diane Roulston. Dr. Anastasi is a
hematopathologist and was one of the first pathologists to pioneer the use
of FISH in hematopoietic disorders. Dr. Roulston, a valued colleague, is a
Preface ix
director of the Cancer Cytogenetics Laboratory at the University of Chicago,
working with Drs. Michelle Le Beau and Janet Rowley.
Dr. Susana Raimondi has published extensively on the cytogenetics of
lymphoid malignancies and therefore was a most logical person to write
Chapter 12. Dr. Avery Sandberg is the Editor-in-Chief of Cancer Genetics
and Cytogenetics (CGC), on whose editorial board I have the honor of serv-
ing. Dr. Zhong Chen is the Associate Editor of CGC. These co-authors of
Chapter 13 need little introduction. My colleagues and friends Drs. Herman
Wyandt, Vijay Tonk, and Roger Lebo have many years of experience in the
field of cytogenetics and have done an outstanding job writing Chapter 14.
Chapter 16 focuses on the cytogenetics of transfusion medicine, a topic not
usually covered in a cytogenetics text. Dr. Carolyn Young is the Medical
Director at the Rhode Island Blood Center and is solely responsible for the
transfusion medicine aspect of the chapter.
Whereas the goal of Chapter 17 is to summarize the possible appli-
cations of FISH for the average clinical cytogenetics laboratory of the 1990s,
Chapter 18 (by Gabriela Green et al.) provides a glimpse of whatm ay
become routine in the average clinical cytogenetics laboratory of the future.
The laboratory of co-author Dr. Thomas Ried is one of the top laboratories
in the world and actively conducts cutting-edge research on molecular cy-
togenetic technologies. It was Thomas’s group that first pioneered the tech-
nique of spectral karyotyping (SKY), which has recently generated so much
excitement in the cytogenetics community,
Many cytogenetics texts omit a discussion of specimen preparation and
other preanalytic variables that might affect the quality of cytogenetic test-
ing. Thus, Chapter 19 was commissioned for this purpose, together with
Chapter 20 on quality control and quality assurance issues. Dr.N ancy
Schneider was responsible for suggesting the former and I am pleased that
my colleague and friend, Dr. Jila Khorsand, a very experienced pathologist,
agreed to take on the project. My colleague and friend Dr. Gerald Hoeltge
is a well-known pathologist and cytogeneticist from the Cleveland Clinic.
Few are more qualified than Gerry to write about setting standards in clinical
laboratories. He is the Inter-Regional Commissioner for the Laboratory Ac-
creditation Program of the College of American Pathologists.
In summary, I am indeed fortunate to have so many commitments from
such a large number of distinguished chapter authors, many of whom are
considered top experts in their fields. I have worked very hard to co-ordinate
the chapters so that topics do not significantly overlap. However, a certain
degree of redundancy was deemed valuable for emphasis.
Before closing, I wish to thank Dr. Michele Sinoway and Sandra Be-
berman of Marcel Dekker, Inc., who invited me to be the editor of this
volume. Lia Pelosi and Elizabeth Curione, as production editors, and other