Table Of ContentTHE GENETIC BASIS OF COMMON DISEASES
OXFORD MONOGRAPHS ON MEDICAL GENETICS
General Editors
Arno G. Motulsky Martin Bobrow Peter S. Harper Charles Scriver
Former Editors
J. A. Fraser Roberts C. O. Carter
16. C. R. Scriver and B. Childs: Garrod's inborn factors in disease
18. M. Baraitser: The genetics of neurological disorders
19. R. J. Gorlin, M. M. Cohen, Jr., and L. S. Levin: Syndromes of the head and neck, third edition
21. D. Warburton, J. Byrne, and N. Canki: Chromosome anomalies and prenatal development: an atlas
22. J. J. Nora, K. Berg, and A. H. Nora: Cardiovascular diseases: genetics, epidemiology, and prevention
24. A. E. H. Emery: Duchenne muscular dystrophy, second edition
25. E. G. D. Tuddenham and D. N. Cooper: The molecular genetics of haemostasis and its inherited disorders
26. A. Boue: Fetal medicine
27. R. E. Stevenson, J. G. Hall, and R. M. Goodman: Human malformations
28. R. J. Gorlin, H. V. Toriello, and M. M. Cohen, Jr.: Hereditary hearing loss and its syndromes
29. R. J. M. Gardner and G. R. Sutherland: Chromosome abnormalities and genetic counseling, second edition
30. A. S. Teebi and T. I. Farag: Genetic disorders among Arab populations
31. M. M. Cohen, Jr.: The child with multiple birth defects
32. W. W. Weber: Pharmacogenetics
33. V. P. Sybert: Genetic skin disorders
34. M. Baraitser: Genetics of neurological disorders, third edition
35. H. Ostrer: Non-mendelian genetics in humans
36. E. Traboulsi: Genetic diseases of the eye
37. G. L. Semenza: Transcription factors and human disease
38. L. Pinsky, R. P. Erickson, and R. N. Schimke: Genetic disorders of human sexual development
39. R. E. Stevenson, C. E. Schwartz, and R. J. Schroer: X-linked mental retardation
40. M. J. Khoury, W. Burke, and E. Thomson: Genetics and public health in the 21st century
41. J. Weil: Psychosocial genetic counseling
42. R. J. Gorlin, M. M. Cohen, Jr., and R. C. M. Hennekam: Syndromes of the head and neck, fourth edition
43. M. M. Cohen, Jr., G. Neri, and R. Weksberg: Overgrowth syndromes
44. R. A. King, J. I. Rotter, and A. G. Motulsky: The genetic basis of common diseases, second edition
OXFORD MONOGRAPHS ON MEDICAL GENETICS NO. 44
The Genetic Basis of
Common Diseases
Second Edition
Edited by
RICHARD A. KING
University of Minnesota
JEROME I. ROTTER
Cedars-Sinai Medical Center and UCLA
ARNO G. MOTULSKY
University of Washington
OXPORD
UNIVERSITY PRESS
2002
OXFORD
UNIVERSITY PRESS
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Copyright © 2002 by Oxford University Press, Inc.
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All rights reserved. No part of this publication may be reproduced,
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Library of Congress Cataloging-in-Publication Data
The genetic basis of common diseases / edited by Richard A. King, Jerome I. Rotter,
Arno G. Motulsky.—2nd ed.
p. ; cm.—(Oxford monographs on medical genetics ; no. 44)
Includes bibliographical references and index.
ISBN 0-19-512582-7
1. Medical genetics. 2. Genetic disorders. I. King, Richard A. (Richard Allen), 1939-
II. Rotter, Jerome I. III. Motulsky, Arno G., 1923- IV. Series.
[DNLM: I. Genetics, Medical. 2. Genetic Diseases, Inborn—genetics. 3. Genetic
Predisposition to Disease. QZ 50 G3226 2002]
RBI55 .G3593 2002
616'.042—dc21
2002018390
1 23456789
Printed in the United States of America
on acid-free paper
PREFACE TO THE SECOND EDITION
Ten years have elapsed since the first edition of this book ap- To accomplish this goal, the second edition of The Genetic
peared. At that time, the promise of better genetic understand- Basis of Common Diseases has grown from 46 to 55 chapters.
ing of common complex diseases had only recently emerged. More importantly, it has been almost completely rewritten. There
The 1992 volume was a first attempt to describe genetic aspects are 20 entirely new chapters, reflecting advances in diseases
of many of these diseases under one cover. The search for genes whose genetic knowledge was rudimentary at the time of the first
underlying common diseases has now become one of the most edition. In a few cases, chapters have been combined, while other
active areas of biomedical research and is supported by the gov- chapters have been divided. New chapters for specific diseases
ernment and nonprofit foundations as well as by the biotech- cover gallstones, hemochromatosis, osteoporosis, spondy-
nology and pharmaceutical industries. loarthrophies, lupus erythematosis, mental retardation, common
The Human Genome Project has provided an almost com- skin diseases and skin cancer, prostate cancer, hearing loss, and
plete sequence of the human genome and, together with novel migraine. New general chapters address topics such as genetic
methods of population genetics and statistics, is ready to be used counseling, evolution and disease, genetic effects of therapy,
for finding genes involved in complex multigenic diseases. New pharmacogenetics, and the role of mitochondrial variation. The
techniques involving the use of DNA markers such as single nu- authorship is virtually completely changed; close to 90% of the
cleotide polymorphisms (SNPs) are being applied more widely authors (103 out of 117) are new.
and include haplotypic combinations of SNPs in a given chro- This second edition should be useful to readers with a clin-
mosomal region. Knowledge of the genetic basis of common dis- ical, genetic, or epidemiologic orientation who want to learn
ease is expanding and is increasingly brought to the clinic. Cur- more about the genetics of common diseases or who can put
rent excitement must be tempered, however, by the complexity this information to practical use in an increasing number of con-
of the problems: the difficulty in identifying susceptibility genes ditions. We hope that the presentation of current knowledge will
of modest effect, the large scale of the required family studies, lead to novel biomedical and genetic research that brings bet-
the difficulty in proving that a provisionally identified gene is ter understanding, prevention, and treatment of these diseases
indeed responsible for susceptibility, and delineating the mech- that constitute the majority of adult illnesses in the developed
anisms by which implicated genes cause clinical disease. Thus, world.
genetic elucidation of complex diseases has been slower than
some observers had hoped for. While we are learning more about
the role of various genes in complex diseases, the isolation of
specific genes that were localized by linkage studies in complex Minneapolis, Minnesota R.A.K.
diseases has been arduous and remains difficult. It is the goal of Los Angeles, California J.I.R.
this second edition to convey current knowledge, excitement, and Seattle, Washington A.G.M.
balance. June 2002
V
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CONTENTS
Contributors, ix 12. IgA Deficiency and Common Variable
Immunodeficiency, 210
Harry W. Schroeder, Jr.
Part I Approaches
1. Approach to Genetic Basis of Common Diseases, 3 Part IV Gastrointestinal Disorders
Richard A. King, Jerome I. Rotter, and Arno G. Motulsky
13. Peptic Ulcer and Gastritis, 229
2. Molecular Genetics of Common Disease, 18 A.S. Pena
Jeffrey R. Smith, Thomas D. Gelehrter, and
14. Lactase Deficiency: Biological and Medical Aspects of
Francis S. Collins
the Adult Human Lactase Polymorphism, 250
3. Genetic Epidemiologic Methods, 39 Edward J. Hollox and Dallas M. Swallow
Stephen S. Rich and Thomas A. Sellers
15. Inflammatory Bowel Disease, 266
4. Evolution of Human Genetic Diseases, 50 Huiying Yang, Kent D. Taylor, and Jerome I. Rotter
Jared Diamond and Jerome L Rotter
16. Gallstones, 298
5. Animal Models of Complex Genetic Disease, 65 Beverly Paigen and Martin C. Carey
Aldons J. Lusis, David West, and Richard C. Davis
17. Chronic Liver Disease, 336
6. Genetic Counseling: History, Risk Assessment, Albert J. Czaja
Strategies, and Ethical Considerations, 87
18. Hereditary Hemochromatosis, 366
Bonnie S. LeRoy and Ann P. Walker
Frances Busfield, G.J. Anderson, and L. W. Powell
19. Gluten-Sensitive Enteropathy, 382
Part II Cardiopulmonary Diseases
Susan L. Neuhausen and John J. Zone
7. Genetics of Coronary Atherosclerosis, 105
Arno G. Motulsky and John D. Brunzell
Part V Endocrine Disorders
8. Hypertension, 127
20. Thyroid Disease, 397
Steven C. Hunt, Paul N. Hopkins, and
Stefan K.G. Grebe
Jean-Marc Lalouel
21. Type 1 Diabetes Mellitus, 431
9. Chronic Obstructive Pulmonary Disease, 155
Leslie J. Raffel and Jerome I. Rotter
Francine Kauffmann and Florence Demenais
22. Type 2 Diabetes Mellitus, 457
Steven C. Elbein, Ken C. Chiu, and M. Alan Permutt
Part III Immunologic and Infectious Diseases
23. Obesity, 481
10. Genetics of Human Susceptibility to Infectious Diseases:
George Bray and Claude Bouchard
Progress and Prospects, 181
Ellen Buschman, Emil Skamene, and Erwin Schurr 24. Genetics of Osteoporosis, 510
Tatiana Foroud, Michael J. Econs,
11. Genetics of Asthma and Bronchial
and C. Conrad Johnston, Jr.
Hyperresponsiveness, 198
Deborah A. Meyers, Denise G. Wiesch, 25. Hyperuricemia and Gout, 518
and Eugene R. Bleecker Michael A. Becker
vii
viii Contents
Part VI Genitourinary Disorders 42. Multiple Sclerosis, 805
Leena Peltonen, Janna Saarela, and Satu Kuokkanen
26. Gynecologic Disorders, 539
Joe Leigh Simpson 43. Alzheimer's Disease, 818
Margaret A. Pericak-Vance and Jonathan L. Haines
27. Infertility and Pregnancy Loss, 554
Carole Ober, M.S. Verp, K.P. Roberts, and J.L. Pry or 44. Affective Disorders, 831
Sevilla D. Detera-Wadleigh and Lynn R. Goldin
Part VII Rheumatologic Diseases 45. Schizophrenia, 850
Ann E. Pulver, Godfrey D. Pearlson, John A. McGrath,
28. Immunology and Immunogenetics, 573
Virginia K. Lasseter, Karen L. Swartz,
Gerald T. Nepom and Henry A. Erlich
and George Papadimitriou
29. Rheumatoid Arthritis, 587
46. Alcoholism, 876
Barbara Nepom and Richard A. King
Dharam P. Agarwal
30. Seronegative Spondyloarthropathies, 604
47. Mental Retardation, 914
R. Hal Scofield
W. Ted Brown
31. Genetics of Systemic Lupus Erythematosus, 612
48. Hereditary Hearing Loss, 920
Patrick M. Gaffney, Richard A. King,
Rena Ellen Falk and Nathan Fischel-Ghodsian
and Timothy W. Behrens
49. Migraine, 935
32. Genetic Basis of Primary Osteoarthritis, 629
Aarno Palotie, Robert Baloh, and Maija Wessman
John Loughlin and Kay Chapman
33. Common Disorders of Connective Tissue, 638
Reed E. Pyeritz
Part X Other Common Problems
Part VIII Cancer 50. Common Skin Diseases, 951
Virginia P. Sybert
34. Gastrointestinal Cancer, 649
Randall W. Burt 51. Genetic Modulation of Aging and Longevity, 964
George M. Martin
35. Breast Cancer, 670
Katherine L. Nathanson and Barbara L. Weber 52. Mitochondrial Defects in Common Diseases, 975
Douglas C. Wallace and Marie T. Lott
36. Familial and Genetic Influences on Risk of Lung
Cancer, 700 53. Constitutional Chromosome Disorders in Adults, 989
Thomas A. Sellers and Ping Yang Georgia L. Wiesner, David B. Everman,
and Suzanne B. Cassidy
37. Reproductive Organ Cancers, 713
Maren T. Scheuner and Beth Y. Karlan
38. Skin Cancer, 724
Allen E. Bale, Suzanne J. Brown, and William D. Posten Part XI Therapy
39. Prostate Cancer, 738 54. Genetic Consequences of Modern Therapeutics:
William B. Isaacs and Jianfeng Xu latrogenic Mutagenesis, 1023
John J. Mulvihill, Sarah F. Whitton,
40. Hematologic Cancer, 749
and Patrick H. Horn
Marshall Horwitz
55. Pharmacogenetics, Ecogenetics, and
Pharmacogenomics, 1033
Part IX Neuropsychiatric Disorders
Werner Kalow
41. Epilepsy, 779
Magali Fernandez and Thomas D. Bird Index, 1041
CONTRIBUTORS
Dharam P. Agarwal, Ph.D., D.Sc. Eugene R. Bleecker, M.D.
Institute of Human Genetics Center for Human Genomics
School of Medicine Department of Medicine
University of Hamburg Wake Forest University School of Medicine
Hamburg, Germany Winston-Salem, North Carolina
Gregory J. Anderson, Ph.D. Claude Bouchard, Ph.D.
Iron Metabolism Laboratory George A. Bray Professor
Queensland Institute of Medical Research Executive Director
Brisbane, Australia Pennington Biomedical Research Center
Louisiana State University
Allen E. Bale, M.D. Baton Rouge, Louisiana
Department of Genetics
Yale University George Bray, M.D.
School of Medicine Boyd Professor
New Haven, Connecticut Pennington Biomedical Research Center
Louisiana State University
Robert Baloh, M.D. Baton Rouge, Louisiana
Department of Neurology
University of California, Los Angeles Suzanne J. Brown, M.D.
School of Medicine Department of Internal Medicine
Los Angeles, California Yale University
School of Medicine
Michael A. Becker, M.D. New Haven, Connecticut
Rheumatology Section
Department of Medicine W. Ted Brown, M.D., Ph.D.
The University of Chicago State University of New York
Pritzker School of Medicine Downstate Medical Center
Chicago, Illinois Brooklyn, New York
Timothy W. Behrens, M.D. John D. Brunzell, M.D.
Department of Medicine Department of Medicine
University of Minnesota Medical School Division of Metabolism, Endocrinology, and Nutrition
Minneapolis, Minnesota University of Washington
School of Medicine
Thomas D. Bird, M.D. Seattle, Washington
Departments of Neurology and Medicine
University of Washington Randall W. Burt, M.D.
School of Medicine Huntsman Cancer Institute
VA Medical Center University of Utah
Seattle, Washington Salt Lake City, Utah
ix
