Medical Genetics, 5e

371 Pages·2015·50.646 MB·English

by  Lynn B. Jorde PhD, John C. Carey MD MPH, Michael J. Bamshad MD

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M E D I C A L
G E N E T I C S
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M E D I C A L
G E N E T I C S
FIFTH EDITION
Lynn B. Jorde,
PhD
Professor
H.A. and Edna Benning Presidential Chair
Department of Human Genetics
University of Utah Health Sciences Center
Salt Lake City, Utah
John C. Carey,
MD, MPH
Professor
Division of Medical Genetics
Department of Pediatrics
University of Utah Health Sciences Center
Salt Lake City, Utah
Michael J. Bamshad,
MD
Professor
Division of Genetic Medicine
Department of Pediatrics
University of Washington School of Medicine
Seattle Children’s Hospital
Seattle, Washington
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
MEDICAL GENETICS, FIFTH EDITION ISBN: 978-0-323-18835-7
Copyright © 2016 by Elsevier, Inc. All rights reserved.
Copyright © 2010, 2006, 2003, 2000, 1995 by Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.
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This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein).
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden
our understanding, changes in research methods, professional practices, or medical treatment may become
necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and
using any information, methods, compounds, or experiments described herein. In using such information
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Library of Congress Cataloging-in-Publication Data
Jorde, Lynn B., author.
Medical genetics / Lynn B. Jorde, John C. Carey, Michael J. Bamshad.—Fifth edition.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-323-18835-7 (pbk. : alk. paper)
I. Carey, John C., 1946- , author. II. Bamshad, Michael J., author. III. Title.
[DNLM: 1. Genetic Diseases, Inborn—genetics. 2. Genetics, Medical—methods. 3. Genetic
Counseling. 4. Genetic Predisposition to Disease. 5. Genetic Techniques. QZ 50]
RB155
616'.042—dc23
2015019218
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Printed in Canada
Last digit is the print number: 9 8 7 6 5 4 3 2 1
To Our Families
Debra, Eileen, and Alton Jorde
Leslie, Patrick, and Andrew Carey
Jerry and Joanne Bamshad
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F O R E WO R D
J.B.S. Haldane titled an anthology of some of his more dys- 20th centuries: What is the relationship between evolution
peptic writings “Everything Has a History,” and this is clearly and development?
applicable to the field of medical genetics. More than 200 In 1945 the University of Utah established the Laboratory
years ago, scientists such as Buffon, Lamarck, Goethe, and for the Study of Hereditary and Metabolic Disorders (later
Kielmeyer reflected on how the developmental history of called the Laboratory of Human Genetics). Here, an out-
each organism relates to the history of life on Earth. Based standing group of scientists performed pioneering studies on
on these ideas, the discipline of biology was born in 18th clefts of lips and palate, muscular dystrophy, albinism, deaf-
century Europe, enjoyed adolescence as morphology and ness, hereditary polyposis of the colon (Gardner syndrome),
comparative anatomy in the 19th century, and reached and familial breast cancer. These predecessors would be enor-
adulthood in the 20th century as the field of genetics. mously proud of their current peers at the University of Utah,
However, the late 19th century definition of genetics (hered- whose successes have advanced knowledge in every aspect of
ity) as the science of variation (and its causes) is still valid. the field of genetics.
Thus, human genetics is the science of human variation, In their attempts to synthesize the story of genetics and its
medical genetics the science of abnormal human variation, applications to human variability, health and disease, devel-
and clinical genetics that branch of medicine that cares for opment, and cancer, the authors of this text have succeeded
individuals and families with abnormal variation of struc- admirably. This concise, well-written, well-illustrated, and
ture and function. carefully edited and indexed book is highly recommended to
In the late 19th and early 20th centuries, the unity of undergraduate students, new graduate students, medical stu-
morphology-based science was gradually replaced by a plu- dents, genetic counseling students, nursing students, and stu-
ralistic view of biology that splintered the field into many dents in the allied health sciences. Importantly, it is also a
different, and often rivalrous, disciplines. However, thanks wonderful text for practicing physicians (primary care pro-
to the application of novel molecular biological methods viders and specialists) who want an authoritative introduc-
to the analysis of development and to the understanding tion to the basis and principles of modern genetics as applied
of the materials of heredity (i.e., genes), the various branches to human health and development. This text, written by dis-
of biology are being reunited. This new discipline, termed tinguished and internationally respected colleagues and
“molecular morphology,” may be defined as the study of the friends who love to teach, is a joy to read in its expression
form, formation, transformation, and malformation of living of enthusiasm and of wonder, which Aristotle said was the
organisms. Indeed, ignorant as they may be of the traditional beginning of all knowledge.
methods of historiography, geneticists have developed their Einstein once said, “The most incomprehensible thing
own brilliant and highly effective methods. Consequently, about the world is that it is comprehensible.” When I began
they have achieved a perspective remarkably longer and much to work in the field of medical genetics, the gene was widely
better documented than that of historians. This nearly 4- viewed as incomprehensible. Indeed, some scientists, such as
billion-year perspective unites living organisms into a single Goldschmidt, cast doubt on the very existence of the gene,
web of life related to one another in unbroken descent to a although the great American biologist E.B. Wilson had pre-
common ancestor. This makes the phylogenetic (i.e., the dicted its chemical nature more than 100 years previously. In
genetic relationships of different species to one another) and this text, genes and their function in health and disease are
the ontogenetic (i.e., the genetic basis for the development of made comprehensible in a manner that should have wide
individual organisms) perspectives of development not only appeal to all.
complementary but inseparable. Thus, it is now possible to John Opitz, MD
effectively explore a key question of biology of the 19th and Salt Lake City, Utah
vii
P R E FAC E
Medical genetics is a rapidly progressing field. No textbook Several pedagogical aids are incorporated in this book:
can remain factually current for long, so we have attempted • Clinical Commentary boxes present detailed coverage of
to emphasize the central principles of genetics and their clini- the most important genetic diseases and provide examples
cal application. In particular, this textbook integrates recent of modern clinical management.
developments in molecular genetics and genomics with clini- • Mini-summaries, highlighted in gold, are placed on nearly
cal practice. every page to help the reader understand and summarize
This new edition maintains the format and presentation important concepts.
that were well received in four previous editions. Basic prin- • Study questions, provided at the end of each chapter, assist
ciples of molecular biology are introduced early in the book the reader in review and comprehension.
so that they can be discussed and applied in subsequent chap- • A detailed glossary is included at the end of the book.
ters. The chapters on autosomal and X-linked disorders • Key terms are emphasized in boldface.
include updated discussions of topics such as genomic • Important up-to-date suggested readings are listed at the
imprinting, anticipation, and expanded trinucleotide repeats. end of each chapter.
The chapter on cytogenetics highlights important advances In addition, the fifth edition retains these important
in this area, including array comparative genomic hybridiza- features:
tion and newly described microdeletion syndromes. Whole- • All chapters have been thoroughly updated, with special
genome DNA sequencing and disease-gene identification, attention given to rapidly changing topics such as high-
which constitute a central focus of modern medical genetics, throughput DNA sequencing, genetic diagnosis, gene
are treated at length. Chapters are included on the rapidly therapy, cancer genetics, and the genetics of other common
developing fields of immunogenetics and cancer genetics. diseases.
Considerable discussion is devoted to the genetics of common • To facilitate the creation of illustrations for teaching pur-
adult diseases, such as heart disease, diabetes, stroke, and poses, all images on the website (including line drawings
hypertension. The book concludes with chapters on genetic from the textbook) can be downloaded.
diagnosis (again emphasizing current approaches such as • An expanded comprehensive index includes all text cita-
whole-exome and whole-genome sequencing), gene therapy, tions of all diseases.
personalized medicine, and clinical genetics and genetic This textbook evolved from courses we teach for medical
counseling. students, nursing students, genetic counseling students, and
As in previous editions, a website is available to provide graduate and undergraduate students in human genetics.
access to continually changing information in medical genet- These students are the primary audience for this book, but it
ics (http://evolve.elsevier.com/Jorde/). The website includes should also be useful for house staff, physicians, and other
downloadable versions of all of the figures in the textbook, health-care professionals who wish to become more familiar
hyperlinks to other relevant sites, and a battery of test ques- with medical genetics.
tions and answers.
viii