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ELSEVIER’S INTEGRATED REVIEW GENETICS This page intentionally left blank ELSEVIER’S INTEGRATED REVIEW GENETICS SECOND EDITION Linda R. Adkison, PhD Professor of Genetics Associate Dean for Curricular Affairs Kansas City University of Medicine and Biosciences Kansas City, Missouri 1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899 ELSEVIER’S INTEGRATED REVIEW GENETICS ISBN: 978-0-323-07448-3 Copyright © 2012, 2007 by Saunders, an imprint of Elsevier, Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. 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 or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. 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Library of Congress Cataloging-in-Publication Data Adkison, Linda R. Elsevier’s integrated review genetics / Linda R. Adkison.—2nd ed. p. ; cm.—(Elsevier’s integrated series) Integrated review genetics Rev. ed. of: Elsevier’s integrated genetics / Linda R. Adkison, Michael D. Brown. c2007. Includes bibliographical references and index. ISBN 978-0-323-07448-3 (pbk. : alk. paper) 1. Medical genetics. I. Adkison, Linda R. Elsevier’s integrated genetics. II. Title. III. Title: Integrated review genetics. IV. Series: Elsevier’s integrated series. [DNLM: 1. Genetics, Medical. QZ 50] RB155.A2565 2012 616′.042—dc22 2011004253 Acquisitions Editor: Madelene Hyde Developmental Editor: Andrea Vosburgh Publishing Services Manager: Pat Joiner-Myers Project Manager: Marlene Weeks Design Direction: Steven Stave Working together to grow libraries in developing countries Printed in China www.elsevier.com | www.bookaid.org | www.sabre.org Last digit is the print number: 9 8 7 6 5 4 3 2 1 I have been fortunate to have excellent mentors during my career in academics. I have learned a great deal about my own learning through this journey. My goals as a teacher are to help students become challenged by the fascination of learning, visualize what they cannot necessarily see, and describe what they see with integration of thought broadly across disciplines. This textbook is dedicated to the many wonderful students and colleagues who constantly challenge the boundaries of learning – theirs and mine. Finally, without the support and understanding of my family, especially my children, Emily and Seth, this project could not have been completed. Linda R. Adkison, PhD This page intentionally left blank vii Preface Though the youngest of all the medical specialties, genetics explains better the morphologic variation observed in embry- embodies the essence of all normal and abnormal develop- ologic development and anatomic presentation. It provides ment and all normal and disease states. Perhaps because of better insight into susceptibility to infection and disease. It its recent recognition as a discipline and perhaps because of offers insight into neurologic and behavioral abnormalities. It its derivation from research in several areas, it is easier for is defining the strategies for gene therapy and pharmacoge- genetics to be an “integrated” discipline. Approaching genet- nomics. For these reasons, it has been exciting to put this ics as “a particular gene located on a specific chromosome book together. and inherited in a specific manner” loses the appreciation of This text focuses on well-known and better described dis- spatial and temporal dimensions of expression and the many, eases and disorders that students and practitioners are likely many factors affecting every single aspect of development, to read about in other references. Many of these do not occur survival, and even death. at a high frequency in populations, but they underscore major Every medical discipline is connected to human well-being mechanisms and major concepts associated with many other through the mechanisms of gene expression, environmental medical situations. It is my hope that this text will be as influences, and inheritance. Genetics underscores the many stimulating to read as it was to write. biochemical pathways, physiologic processes, and pathologic mechanisms presented in other volumes of this series. It Linda R. Adkison, PhD viii Editorial Review Board Chief Series Advisor James L. Hiatt, PhD Professor Emeritus J. Hurley Myers, PhD Department of Biomedical Sciences Professor Emeritus of Physiology and Medicine Baltimore College of Dental Surgery Southern Illinois University School of Medicine; Dental School President and CEO University of Maryland at Baltimore DxR Development Group, Inc. Baltimore, Maryland Carbondale, Illinois Immunology Anatomy and Embryology Darren G. Woodside, PhD Thomas R. Gest, PhD Principal Scientist University of Michigan Medical School Drug Discovery Division of Anatomical Sciences Encysive Pharmaceuticals, Inc. Office of Medical Education Houston, Texas Ann Arbor, Michigan Microbiology Biochemistry Richard C. Hunt, MA, PhD John W. Baynes, MS, PhD Professor of Pathology, Microbiology, and Immunology Graduate Science Research Center Director of the Biomedical Sciences Graduate Program University of South Carolina Department of Pathology and Microbiology Columbia, South Carolina University of South Carolina School of Medicine Marek Dominiczak, MD, PhD, FRCPath, FRCP(Glas) Columbia, South Carolina Clinical Biochemistry Service NHS Greater Glasgow and Clyde Neuroscience Gartnavel General Hospital Cristian Stefan, MD Glasgow, United Kingdom Associate Professor Department of Cell Biology Clinical Medicine University of Massachusetts Medical School Ted O’Connell, MD Worcester, Massachusetts Clinical Instructor David Geffen School of Medicine Pathology UCLA; Peter G. Anderson, DVM, PhD Program Director Professor and Director of Pathology Undergraduate Woodland Hills Family Medicine Residency Program Education Woodland Hills, California Department of Pathology University of Alabama at Birmingham Genetics Birmingham, Alabama Neil E. Lamb, PhD Director of Educational Outreach Pharmacology Hudson Alpha Institute for Biotechnology Michael M. White, PhD Huntsville, Alabama; Professor Adjunct Professor Department of Pharmacology and Physiology Department of Human Genetics Drexel University College of Medicine Emory University Philadelphia, Pennsylvania Atlanta, Georgia Physiology Histology Joel Michael, PhD Leslie P. Gartner, PhD Department of Molecular Biophysics and Physiology Professor of Anatomy Rush Medical College Department of Biomedical Sciences Chicago, Illinois Baltimore College of Dental Surgery Dental School University of Maryland at Baltimore Baltimore, Maryland ix Contents 1 BASIC MECHANISMS 1 2 CHROMOSOMES IN THE CELL 12 3 MECHANISMS OF INHERITANCE 28 4 GENETICS OF METABOLIC DISORDERS 51 5 CANCER GENETICS 65 6 HEMATOLOGIC GENETICS AND DISORDERS 93 7 MUSCULOSKELETAL DISORDERS 114 8 NEUROLOGIC DISEASES 133 9 CARDIOPULMONARY DISORDERS 159 10 RENAL, GASTROINTESTINAL, AND HEPATIC DISORDERS 177 11 DISORDERS OF SEXUAL DIFFERENTIATION AND DEVELOPMENT 192 12 POPULATION GENETICS AND MEDICINE 209 13 MODERN MOLECULAR MEDICINE 217 INDEX 239 Case Studies and Case Study Answers are available online on Student Consult www.studentconsult.com