Molecular and Translational Medicine Series Editors William B. Coleman Gregory J. Tsongalis For further volumes: http://www.springer.com/series/8176
D. Hunter Best Jeffrey J. Swensen Editors Molecular Genetics and Personalized Medicine
Editors D. Hunter Best, Ph.D., FACMG Department of Pathology University of Utah School of Medicine Salt Lake City, UT 84112-0565 hunter.best@aruplab.com Jeffrey J. Swensen, Ph.D., FACMG Department of Pathology University of Utah School of Medicine Salt Lake City, UT 84112-0565, USA jeffrey.swensen@aruplab.com ISBN 978-1-61779-529-9 e-isbn 978-1-61779-530-5 DOI 10.1007/978-1-61779-530-5 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2011943887 Springer Science+Business Media, LLC 2012 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Humana Press is part of Springer Science+Business Media (www.springer.com)
Preface Just under 10 years ago, the first draft of the human genome sequence was completed, officially starting the era of genomic medicine. In the decade that has followed, this knowledge has fueled revolutionary technological advances that allow medicine to be personalized to the individual patient. Genetic testing has become commonplace, and clinicians are frequently able to use knowledge of an individual s specific genetic differences to guide their course of action. However, understanding the complexities involved in molecular genetic testing is difficult and can be intimidating. In this volume, we have sought to simplify some of the complex issues that arise when dealing with molecular genetic testing. Topics covered include everything from a description of the basic molecular methods used to perform molecular testing to genetic counseling and presymptomatic genetic testing. Each chapter is written by an expert in their field in a manner that is accessible to individuals with very little background in genetics. In addition, the authors have tried to focus on practical patient-related issues that commonly present themselves to today s practicing physician. While we realize that this text is by no means a comprehensive review of the field of molecular genetics, we do feel it will serve as a useful reference for physicians hoping to better understand the role of molecular medicine in clinical practice. Furthermore, we hope it will prove to be an invaluable resource for the basic scientist that wants to better understand how advances in the laboratory are being moved from the bench to the bedside. Sincerely, D. Hunter Best Jeffrey J. Swensen v
Contents 1 Molecular Genetic Testing in the Genomic Era... 1 Charles J. Sailey and Ferrin C. Wheeler 2 Array Comparative Genomic Hybridization in Cytogenetics and Molecular Genetics... 21 S. Hussain Askree and Madhuri R. Hegde 3 Pharmacogenomics: Tailoring Treatment Based on Genotype... 37 Alan H.B. Wu 4 Somatic Alterations and Targeted Therapy... 51 Allison M. Cushman-Vokoun 5 Genome-Wide Association Studies in Disease Risk Calculation: The Role of Bioinformatics in Patient Care... 103 Todd L. Edwards, Digna R. Velez Edwards, and Marylyn DeRiggi Ritchie 6 Presymptomatic Genetic Testing: Shifting the Emphasis from Reaction to Prevention... 131 Irene H. Hung and John C. Carey 7 Prenatal Testing: Screening, Diagnosis, and Preimplantation Genetic Diagnosis... 147 Eugene Pergament 8 Newborn Screening for Metabolic Disorders... 163 Marzia Pasquali and Nicola Longo 9 The Role of Genetic Counseling in Everyday Medical Practice... 199 Kimberly J. Hart, Erin E. Baldwin, and D. Hunter Best 10 Direct-to-Consumer Genetic Testing... 215 Caroline F. Wright and Daniel G. MacArthur Index... 237 vii
Contributors S. Hussain Askree, Ph.D., M.B.B.S. Emory Genetics Laboratory, Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA Erin E. Baldwin, M.S. Department of Genetics, ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA D. Hunter Best, Ph.D., FACMG Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA John C. Carey, M.D., M.P.H. Division of Medical Genetics, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA Allison M. Cushman-Vokoun, M.D., Ph.D. Department of Pathology & Microbiology, University of Nebraska Medical Center, Omaha, NE, USA Todd L. Edwards, Ph.D. Center for Human Genetics Research, Vanderbilt Medical Center, Vanderbilt University, Nashville, TN, USA Digna R. Velez Edwards, Ph.D. Division of Epidemiology, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN, USA Kimberly J. Hart, M.S. Department of Genetics, ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA Madhuri R. Hegde, Ph.D., FACMG Emory Genetics Laboratory, Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA Irene H. Hung, M.D. Division of Medical Genetics, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA ix
x Contributors Nicola Longo, M.D., Ph.D. Division of Medical Genetics, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA Daniel G. MacArthur, Ph.D. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK Marzia Pasquali, Ph.D., FACMG Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT, USA Eugene Pergament, M.D., Ph.D., FACMG Northwestern Reproductive Genetics, Inc., and Department of Obstetrics and Gynecology Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Marylyn DeRiggi Ritchie, Ph.D., M.S. Molecular Physiology & Biophysics, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN, USA Charles J. Sailey, M.D., M.S. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA Molecular Genetic Pathology, Arkansas Children s Hospital, Little Rock, AR, USA Jeffrey J. Swensen, Ph.D., FACMG Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA Ferrin C. Wheeler, Ph.D., FACMG Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA Caroline F. Wright, Ph.D. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK Alan H.B. Wu, Ph.D. Department of Laboratory Medicine, San Francisco General Hospital, University of California, San Francisco, CA, USA