M OLECULAR D ISSECTION OF C T OMPLEX RAITS Edited by Andrew H. Paterson, Ph.D. Christine Richardson Professor of Agriculture Department of Soil and Crop Science Texas A&M University College Station, Texas CRC Press Boca Raton New York London Tokyo © 1998 by CRC Press LLC Images used in cover design courtesy of John C. Crabbe and Michael Moody of the Department of Veterans Affairs Medical Center in Portland, Oregon, and Charles W. Stuber of the U.S. Department of Agriculture, Agricultural Research Service, at North Carolina State University in Raleigh. Acquiring Editor: Marsha Baker Project Editor: Carol Whitehead Marketing Manager: Becky McEldowney Cover design: Dawn Boyd PrePress: Kevin Luong Manufacturing: Carol Royal Library of Congress Cataloging-in-Publication Data Molecular dissection of complex traits / edited by Andrew H. Paterson. p. cm. Includes bibliographical references and index. ISBN 0-8493-7686-6 (alk. paper) 1. Molecular genetics. 2. Phenotype. 3. Gene mapping. I. Paterson, Andrew H., 1960- . QH442.M645 1997 572.8--dc21 97-12278 CIP This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval system, without prior permission in writing from the publisher. All rights reserved. Authorization to photocopy items for internal or personal use, or the personal or internal use of specific clients, may be granted by CRC Press LLC, provided that $.50 per page photocopied is paid directly to Copyright Clearance Center, 27 Congress Street, Salem, MA 01970 USA. The fee code for users of the Transactional Reporting Service is ISBN 0-8493-7686-6/98/$0.00+$.50. The fee is subject to change without notice. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. The consent of CRC Press LLC does not extend to copying for general distribution, for promotion, for creating new works, or for resale. Specific permission must be obtained in writing from CRC Press LLC for such copying. Direct all inquiries to CRC Press LLC, 2000 Corporate Blvd., N.W., Boca Raton, Florida 33431. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation, without intent to infringe. © 1998 by CRC Press LLC No claim to original U.S. Government works International Standard Book Number 0-8493-7686-6 Library of Congress Card Number 97-12278 Printed in the United States of America 1 2 3 4 5 6 7 8 9 0 Printed on acid-free paper © 1998 by CRC Press LLC Preface One of the great conflicts in the history of genetics was reconciled with the realization that continuous variation in phenotype could reflect the net effects of a large number of genes. In the past ten years, contemporary geneticists using new molecular tools have been able to resolve complex traits into individual genetic components and describe each such component in much detail. This volume summarizes the state of the art in molecular analysis of complex traits (QTL mapping), placing new developments in this field within the context of their historical origins. Leading authorities address central themes in analysis of complex phenotypes, and case histories of seminal work in this burgeoning field are presented by the principal investigators. Through this volume the authors strive to convey their excitement about a new experimental approach that has empowered us to ask precise questions about complex phenomena. We and our colleagues have, in the past few years, been fortunate to participate in a rare era in the evolution of a field of science — an era in which ne w technology confers the rare opportunity to reinvestigate both classical dogma and speculative proposals that are deeply entrenched in the history of a field. Results to date have begun to clarify ambiguity, in a few cases resolve dichotomy, and in many cases point to the need for still more detailed study. Now is an exciting time to be a geneticist, with unprecedented new opportunities unfolding that we could only dream of a few short years ago. The volume is written primarily for an audience of biologists familiar with genetics and is intended to be useful both to senior scientists in a wide range of biotic disciplines and to entry- level pre- or postdoctoral scientists. Lay people with a scientific bent can readily master the topics presented herein, but it is recommended that they first become more familiar with the underlying methods and principles of genome analysis by reviewing any of several recent reviews. The efficacy with which QTL mapping is done in plants tends to bias the examples chosen; however, several chapters address issues unique to animal systems, including humans. The specific scope and objectives of this volume are: 1. To provide a complete, well-focused volume in the field of molecular genetic analysis of complex phenotypes, including case histories written by leading practitioners in the field. Such a volume will be intended to quickly bring the scientist or student up to the state of the art in an important and rapidly-growing field and to introduce the layman with a scientific bent to a new approach for investigating fundamental questions in the life sciences. 2. To place contemporary technological developments in “molecular quantitative genetics” within the context of their historical origins. Moreover, consider how recent advances in the study of genetics are being applied to better understanding of classical questions. 3. To highlight future needs and directions in utilization of “molecular quantitative genetics” across the biological sciences. The modern capability for molecular dissection of complex phenotypes is capable of addressing a plethora of questions and issues in genetics, breeding, and other areas of the life sciences. This volume will seek to explore efficient approaches to addressing these issues which maximize return on investment of public or private resources. The book is divided into three parts: Chapters 1–12, “Fundamental Principles” are intended to quickly bring the scientist or student up to the state of the art in an important and rapidly-growing field and to introduce © 1998 by CRC Press LLC the layman with a scientific bent to a new approach for investigating fundamental questions in the life sciences. Chapters 13–19, “Case Histories” of seminal work in QTL mapping are intended to show the utility of this new research approach in detailed investigation of a wide range of biological questions. Leading practitioners of molecular dissection reveal the thought processes which led to their seminal results. Chapters 20–21, “Social Impact.” The modern capability for molecular dissection of complex phenotypes is capable of addressing a plethora of questions and issues in genetics, breed- ing, and other areas of the life sciences. These chapters will seek to explore possible long- term impacts of these new research capabilities on agriculture and medicine, respectively. We, the authors, hope that you, the readers, gain a sense of the excitement we enjoy about the possibility of using these new tools and techniques to better describe our own experiments and more generally to better understand the biological world around us. Further, we hope that the contents of this volume are helpful to those of you who seek to join us in this endeavor, and we welcome you into the dynamic field of “molecular quantitative genetics.” Andrew H. Paterson © 1998 by CRC Press LLC Editor Andrew H. Paterson, Ph.D., is the Christine Richardson Professor of Agriculture in the Department of Soil and Crop Sciences and a full member of the Graduate Fields of Genetics and Plant Physiology & Plant Biotechnology at Texas A&M University in College Station, Texas. Dr. Paterson received his B.S. in Plant Science from the University of Delaware, Newark Delaware, in 1982, under the direction of Professors James A. Hawk and Donald L. Sparks. He obtained his M.S. in 1985 and Ph.D. in 1988 from the Department of Plant Breeding and Biometry, Cornell University, Ithaca, New York, under the direction of Professor Mark E. Sorrells. After doing postdoctoral work with Professor Steven D. Tanksley at Cornell University, he joined the Agricul- tural Biotechnology program of E.I. duPont de Nemours as a Research Biologist, and simulta- neously held an Adjunct Assistant Professorship in Plant Molecular Biology at the University of Delaware. In 1991, he joined the Department of Soil and Crop Sciences at Texas A&M University as an Assistant Professor. He received tenure and promotion to Associate Professor in 1995 and was appointed the holder of the Christine Richardson Endowment in 1996. Dr. Paterson is a member of the American Association for the Advancement of Science, the Genetics Society of America, the Crop Science Society of America, the Brazilian Society of Genetics, and the honorary societies Sigma Xi, Phi Kappa Phi, and Gamma Sigma Delta. In 1996, he was named the Young Crop Scientist of the Year by the Crop Science Society of America. He was recently named the Faculty Lecturer of 1997 by Texas A&M University. Dr. Paterson has delivered many invited seminars and symposium talks. He has regularly lectured at the International Plant and Animal Genome Conference, Keystone Symposia, Gordon Conference, Beltwide Cotton Conference, and at many universities and research institutions. Dr. Paterson is currently the recipient of research grants from the United States Department of Agriculture, International Consortium for Sugarcane Biotechnology, Pioneer Hibred International, Texas Higher Education Coordinating Board, and Texas State Support Committee of Cotton, Inc. He has published about 40 refereed papers, contributed chapters to several books, and edited one other volume. His current research interests focus on genome organization and evolution in several higher plant taxa, with particular emphasis on gene manipulation in crop improvement. © 1998 by CRC Press LLC Contributors Kjell Andersson Lon R. Cardon Department of Animal Breeding and Genetics Sequana Therapeutics, Inc. Swedish University of Agricultural Sciences La Jolla, California Uppsala, Sweden Gary A. Churchill Leif Andersson Department of Plant Breeding and Biometry Department of Animal Breeding and Genetics Cornell University Swedish University of Agricultural Sciences Ithaca, New York Uppsala, Sweden John C. Crabbe Lena Andersson-Eklund Portland Alcohol Research Center Department of Animal Breeding and Genetics Department of Veterans Affairs Medical Center Swedish University of Agricultural Sciences and Uppsala, Sweden Department of Behavioral Neuroscience William D. Beavis Oregon Heath Sciences University Quantitative Genetics Group Portland, Oregon Trait and Technology Integration Rebecca W. Doerge Pioneer Hi-Bred International, Inc. Johnston, Iowa Departments of Agronomy and Statistics Purdue University John K. Belknap West Lafayette, Indiana Portland Alcohol Research Center Department of Veterans Affairs Medical Center Inger Edfors-Lilja and Department of Engineering and Natural Sciences Department of Behavioral Neuroscience University of Växjö Oregon Heath Sciences University Växjö, Sweden Portland, Oregon Hans Ellegren Douglas W. Bigwood Department of Animal Breeding and Genetics Department of Plant Biology Swedish University of Agricultural Sciences University of Maryland Uppsala, Sweden College Park, Maryland Yuval Eshed Thomas K. Blake Faculty of Agriculture Department of Plant and Soil Sciences The Hebrew University of Jerusalem Montana State University Rehovot, Israel Bozeman, Montana H. D. Bradshaw, Jr. Michel Georges College of Forest Resources Department of Genetics University of Washington Faculty of Veterinary Medicine Seattle, Washington University of Liege Liege, Belgium Mark D. Burow Department of Soil and Crop Sciences Chris S. Haley Texas A&M University Roslin Institute College Station, Texas Edinburgh, UK © 1998 by CRC Press LLC Ingemar Hansson Susan R. McCouch Department of Food Science Department of Plant Breeding and Biometry Swedish University of Agricultural Sciences Cornell University Uppsala, Sweden Ithaca, New York James E. Irvine Andrew H. Paterson Department of Soil and Crop Science Department of Soil and Crop Sciences Texas A&M Research and Extension Center Texas A&M University Weslaco, Texas College Station, Texas Sara A. Knott Joao L. Rocha Institute of Cell, Animal and Department of Animal Science Population Biology Texas A&M University University of Edinburgh College Station, Texas Edinburgh, UK Hakan Sakul Zhikang Li Sequana Therapeutics, Inc. Department of Soil and Crop Sciences La Jolla, California Texas A&M University College Station, Texas Keith F. Schertz U.S. Department of Agriculture Yann-Rong Lin Agricultural Research Service Department of Soil and Crop Sciences College Station, Texas Texas A&M University College Station, Texas Charles W. Stuber U.S. Department of Agriculture Ben-Hui Liu Agricultural Research Service Department of Forestry Department of Genetics North Carolina State University North Carolina State University Raleigh, North Carolina Raleigh, North Carolina Sin-Chieh Liu Jeremy F. Taylor Department of Soil and Crop Sciences Department of Animal Science Texas A&M University Texas A&M University College Station, Texas College Station, Texas Kerstin Lundström Claire G. Williams Department of Food Science College of Agriculture and Life Sciences Swedish University of Agricultural Sciences Texas A&M University Uppsala, Sweden College Station, Texas Lena Marklund Jinhua Xiao Department of Animal Breeding and Genetics Department of Plant Breeding and Biometry Swedish University of Agricultural Sciences Cornell University Uppsala, Sweden Ithaca, New York Maria Johansson Moller Dani Zamir Department of Animal Breeding and Genetics Faculty of Agriculture Swedish University of Agricultural Sciences The Hebrew University of Jerusalem Uppsala, Sweden Rehovot, Israel © 1998 by CRC Press LLC Contents INTRODUCTION Chapter 1 Of Blending, Beans, and Bristles: The Foundations of QTL Mapping...........................................1 Andrew H. Paterson PART I. FUNDAMENTAL PRINCIPLES Chapter 2 Molecular Tools for the Study of Complex Traits..........................................................................13 Mark D. Burow and Thomas K. Blake Chapter 3 Mapping Quantitative Trait Loci in Experimental Populations......................................................31 Gary A. Churchill and Rebecca W. Doerge Chapter 4 Computational Tools for Study of Complex Traits.........................................................................43 Ben-Hui Liu Chapter 5 QTL Mapping in Outbred Pedigrees...............................................................................................81 Claire G. Williams Chapter 6 Mapping QTLs in Autopolyploids...................................................................................................95 Sin-Chieh Liu, Yann-Rong Lin, James E. Irvine, and Andrew H. Paterson Chapter 7 QTL Analysis under Linkage Equilibrium....................................................................................103 Jeremy F. Taylor and Joao L. Rocha Chapter 8 Molecular Analysis of Epistasis....................................................................................................119 Zhikang Li Chapter 9 QTL Mapping in DNA Marker-Assisted Plant and Animal Improvement..................................131 Andrew H. Paterson © 1998 by CRC Press LLC Chapter 10 QTL Analyses: Power, Precision, and Accuracy...........................................................................145 William D. Beavis Chapter 11 High-Resolution Mapping of QTLs..............................................................................................163 Andrew H. Paterson Chapter 12 Compilation and Distribution of Data on Complex Traits............................................................175 Douglas W. Bigwood PART II. CASE HISTORIES Chapter 13 Case History in Plant Domestication: Sorghum, An Example of Cereal Evolution....................187 Andrew H. Paterson, Keith F. Schertz, Yann-rong Lin, and Zhikang Li Chapter 14 Case History in Crop Improvement: Yield Heterosis in Maize....................................................197 Charles W. Stuber Chapter 15 Case History in Germplasm Introgression: Tomato Genetics and Breeding Using Nearly Isogenic Introgression Lines Derived from Wild Species................................................207 Dani Zamir and Yuval Eshed Chapter 16 Case History in Genetics of Long-Lived Plants: Molecular Approaches to Domestication of a Fast-Growing Forest Tree: Populus...............................................................219 H. D. Bradshaw, Jr. Chapter 17 Case History in Animal Improvement: Mapping Complex Traits in Ruminants.........................229 Michel Georges Chapter 18 Case History in Animal Improvement: Genetic Mapping of QTLs for Growth and Fatness in the Pig...........................................................................................................................241 Leif Andersson, Kjell Andersson, Lena Andersson-Eklund, Inger Edfors-Lilja, Hans Ellegren, Chris S. Haley, Ingemar Hansson, Maria Johansson Moller, Sara A. Knott, Kerstin Lundström, and Lena Marklund Chapter 19 Case History in Humans: Mapping QTLs for Complex Traits in Humans.................................255 Hakan Sakul and Lon R. Cardon © 1998 by CRC Press LLC PART III. SOCIAL IMPACT OF QTL MAPPING Chapter 20 From Malthus to Mapping: Prospects for the Utilization of Genome Analysis to Enhance the World Food Supply..................................................................................................................267 Jinhua Xiao and Susan R. McCouch Chapter 21 Ethical Consequences of Mapping QTLs for Complex Human Traits........................................279 John C. Crabbe and John K. Belknap EPILOGUE Chapter 22 Prospects for Cloning the Genetic Determinants of QTLs...........................................................289 Andrew H. Paterson © 1998 by CRC Press LLC