Table Of ContentPocket Guide to
GENE LEVEL
DIAGNOSTICS
in Clinical Practice
Victor A. Bernstam
BioSol Ltd.
Ann Arbor, Michigan
Boca Raton London New York
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ISBN-13: 978-0-8493-4485-5 (pbk)
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Lihrary of Congress Card Number 92-23745
Library or Congress Cataloging-in-t'ublication Data
Bemstam, Victor A.
POl;ket gUide to gene level diagnostiCS In ,)inical practlr.el Victor A. Bemstam.
p. cm.
Companion v. 10: Handbook of gene level diagnostics 1ll climcal practice I
Victor A. Bernstam. 1992.
Includes mdex.
ISBN 0-8493-4485-9
I. Medical genetic~-Handbooks, manuals, etc. I. Hernstam, Victor
A. Handhook of gene level diagnostics in clinical practice. 11. Title.
{ONLM: j. Genetic Techniques-handbooks. 2. GenetiCS, Medical-meth
ods-handbuok~ 3. Hereditary Disease~- diagnosis---handhooks. 4. Heredi
tary Diseases-genetics-handbooks. 5. Prenatal Diagnosis-methods
handboob. QZ 39 B53lpl
RB l55.B483 1992
616'.042-dc20
DNLMjDLC
for Library of Congress 92-23745
CIP
PREFACE
Developments in the Human Genome Project, the avalanche of changes
in and progressive sophistication of nucleic acid technology occur at
lightning speed. This cannot justify waiting for a better time to take stock
of this everchanging field — if anything, just the opposite is true. The
formerly undreamed of possibilities open up in molecular diagnostics. An
overview of such a vast amount of data can only be selective at any given
time. It may, however, provide a basis for better understanding of the new
dimension that contemporary medicine is assuming.
Both the Handbook and Pocket Guide are intended for students and
residents, physicians of various disciplines, forensic and laboratory scien
tists who are interested in applying molecular biological technology to
patient care. The objective of the Handbook is to provide an overview of
options and spectacular advances in disease evaluation at the gene level. The
condensed Pocket Guide incorporates additional data on
• representative manufacturers of instruments and reagents useful in
molecular diagnostics, including descriptions of selected products
(Supplement 1)
• representative small and larger commercial laboratories offering ser
vices in molecular genetic testing (Supplement 2)
• a listing of the U.S. laboratories already licensed to perform polymerase
chain reaction for human diagnosis at the time of this writing (Supple
ment 3). Listing of such laboratories elsewhere in the world was not
available at the time of this writing
• description of the current efforts of three professional groups in the U.S.
practicing gene level evaluation — human geneticists, pathologists and
forensic scientists — that includes an Executive Summary of the recent
recommendations of the Committee on DNA Technology in Forensic
Science of the National Research Council and Legislative Guidelines for
DNA Databases (Supplements 4 and 5). The latter define not only the
procedural, scientific and legal issues involved, but also address ethical
aspects of DNA testing in forensic practice
Both publications are being continually updated to reflect changes in this
exciting field. I welcome any contributory information, constructive criti
cism, comments, and suggestions helpful in making these vast databases as
useful as possible for patient care.
The production of the Pocket Guide has only become possible due to the
invaluable support and patient cooperation of the CRC staff, particularly
Jeff Holtmeier and Suzanne Lassandro.
I am grateful to all those who appreciated my efforts and found time and
energy in their busy schedule to contribute material for the Supplements.
My special thanks go to Carl W. Bell, George Bers, Joseph A. Chimera,
Jacqueline Cossmon, Ellen Daniell, Paul B. Ferrara, Robert C. Giles, Linda
H. Masterson, Robert M. Nakamura, Michael Mechanic, Nancy Mulzoff,
Patricia Murphy, Joshimi Munch, Deborah J. Oronzio, Roberta A. Pagon,
John P. Richard, Barbara E. Thalenfeld, Stephen N. Thibodeau, Annette
Short, Steve S. Sommer, John M. Sorvillo, Michael S. Watson, and Frank
Witney.
I cannot express enough gratitude to Elmer V. Bemstam for his immense
and creative involvement also with this book, accepting with humor and
stoicism my reliance on his talents at all stages of this project as can only be
expected from a true co-author.
Victor A. Bemstam
Ann Arbor, Michigan
October 1992
The Author
Victor A. Bemstam, President of BioSol, Ltd. (Ann Arbor, MI) received
his M.D. from the Leningrad (now St. Petersburg) Medical Institute, USSR
in 1966, and his Ph.D. in cellular molecular biology from the USSR
Academy of Sciences Komarov Botanical Institute in Leningrad in 1973.
Since 1960 he has conducted research on brain biochemistry, molecular
mechanisms of hormonal induction of gene expression, heat shock effects
on protein biosynthesis, membrane phenomena in experimental and clinical
atherosclerosis, and laboratory diagnostics. Dr. Bemstam has held positions
as a Research Scientist at the Komarov Botanical Institute and the Institute
of Cytology of the USSR Academy of Sciences in Leningrad, as well as in
the Cellular Chemistry Laboratory at the University of Michigan School of
Public Health in Ann Arbor. His medical experience includes work as an
Emergency Physician in Leningrad, and later following American Pathol
ogy Board Certification as a Pathologist concentrating on clinical special
chemistry and molecular pathology. Dr. Bemstam served as a Medical
Director of Chelsea Medical Laboratory, MDS Laboratories, and later was
one of the organizers and, subsequently, Medical Director of Warde
Medical Laboratory (Ann Arbor, MI) where he established and headed a
Molecular Diagnostics Group. He has published and lectured on GABA
metabolism, heat shock research and apolipoprotein testing for coronary
risk assessment. He has developed and patented a novel ligand-removing,
clarifying reagent, Liposol®. He is a member of the College of American
Pathologists, American Association for Clinical Chemistry, New York
Academy of Sciences, and the honorary society Sigma Xi. He continues
research on laboratory diagnostics and consults in molecular diagnostics.
To
Elmer, Luda, and Inna, Luba and Shura
CONTENTS
PART 1: GENERAL ASPECTS OF GENE LEVEL
EVALUATION. SURVEY OF TECHNIQUES AND
APPLICATIONS .........................................................................................1
CHAPTER 1.1 Introduction.....................................................................3
CHAPTER 1.2 A Survey of Newer Gene Probing Techniques........13
CHAPTER 1.3 Prenatal Diagnosis........................................................55
CHAPTER 1.4 Aging..............................................................................67
CHAPTER 1.5 DNA Repair..................................................................71
CHAPTER 1.6 Drug Resistance...........................................................85
CHAPTER 1.7 Metastasis......................................................................89
PART 2: GENE LEVEL EVALUATION OF SELECTED
DISORDERS OF THE HEART, LUNG, GASTROINTESTINAL
TRACT AND TUMORS OF THE HEAD AND NECK ...................93
CHAPTER 2.1 Atherosclerosis and Comonary Heart Disease........95
CHAPTER 2.2 Gastrointestinal Diseases...........................................109
CHAPTER 2.3 Hepatocellular Carcinoma..........................................123
CHAPTER 2.4 Pancreas.......................................................................129
CHAPTER 2.5 Cystic Fibrosis.............................................................133
CHAPTER 2.6 Lung.............................................................................139
CHAPTER 2.7 Tumors of the Head and Neck..................................147
PART 3: GENE LEVEL EVALUATION OF SELECTED
BREAST, GYNECOLOGIC AND UROLOGIC TUMORS ..........151
CHAPTER 3.1 Breast...........................................................................153
CHAPTER 3.2 Tumors of the Uterine Cervix and Endometrium .... 167
CHAPTER 3.3 Ovarian Neoplasms....................................................173
CHAPTER 3.4 Prostrate Neoplasms...................................................177
CHAPTER 3.5 Kidney and Urinary Bladder.....................................181
CHAPTER 3.6 Wilms' Tumor.............................................................189
PART 4: GENE LEVEL EVALUATION OF SELECTED
ENDOCRINE DISORDERS ...............................................................193
CHAPTER 4.1 Diabetes Mellitus.......................................................195
CHAPTER 4.2 Thyroid and Parathyroid Disorders..........................203
CHAPTER 4.3 Adrenal Gland and Multiple Endocrine Neoplasia
1 and 2..........................................................................209
PART 5: GENE LEVEL EVALUATION OF SELECTED
NEUROLOGIC AND CONNECTIVE TISSUE DISORDERS .217
CHAPTER 5.1 Muscle, Bone, and Skin Disorders.............................219
CHAPTER 5.2 Neurological and Mental Disorders...........................237
PART 6: GENE LEVEL EVALUATION OF INFECTIOUS
DISEASES ................................................................................................259
CHAPTER 6.1 Introduction.................................................................261
CHAPTER 6.2 Enteric Pathogens.......................................................267
CHAPTER 6.3 Respiratory Pathogens................................................287
CHAPTER 6.4 Sexually Transmitted Diseases.................................307
CHAPTER 6.5 Pathogens Causing Multisystem Infections.............341
CHAPTER 6.6 Pathogens Transmitted by Arthropods.....................347
CHAPTER 6.7 Parasites .......................................................................351
PART 7: SELECTED METHODOLOGICAL ASPECTS OF
GENE LEVEL EVALUATION IN HEMATOLOGY ...................355
CHAPTER 7.1 Hemoglobinopathies..................................................357
CHAPTER 7.2 Coagulopathies............................................................361
CHAPTER 7.3 Lymphoid and Myeloid Malignancies.....................365
SUPPLEMENT 1: MANUFACTURERS ......................................381
Commercial Sources of Molecular Biological Reagents and
Diagnostics.................................................................................................383
SUPPLEMENT 2: TESTING LABORATORIES .......................447
Selected Laboratories Offering Testing Services in Molecular Genetics
and Diagnosis of Infectious Diseases at the Gene Level.......................449
SUPPLEMENT 3: PCR LICENSEES .............................................461
Institutions in the U.S. Licensed by Roche Molecular Systems to
Perform Human Diagnostic Services by Polymerase Chain Reaction
Technology.................................................................................................463
SUPPLEMENT 4: EFFORTS OF PROFESSIONAL
ORGANIZATIONS ...............................................................................465
Medical Genetics: the Current State of the Field...................................467
Quality Assurance in Clinical Laboratory Molecular Pathology
Testing.........................................................................................................471
SUPPLEMENT 5: DNA IN FORENSIC PRACTICE ................475
DNA: Technology in Forensic Science: Executive Summary..............477
Legislative Guidelines for DNA Databases............................................503
INDEX........................................................................................................517
