Respiratory Genetics PDF

Preface

The impressive success of the Human Genome Project and the identification of the genetic basis for many monogenic disorders have generated a great deal of interest in genetic research among scientists and clinicians. However, we are at the beginning of the application of new genetic technology to pulmonary disease. New tools, methods and resources are needed to bring the full potential of genetics to the point of clinical relevance for complex traits. An additional issue is that the multidisciplinary nature of genetic research, which includes molecular biology, epidemiology, statistical genetics, and bioinformatics, has limited the accessibility of genetic approaches to many pulmonary researchers and physicians. Even among genetic researchers, no single investigator can have complete mastery of clinical phenotyping, molecular characterization, and statistical genetic approaches.

Our goals in this book are to provide an introduction to the major fields and genetic approaches to respiratory disorders (Chapters 1 to 8), and to provide an integrated discussion of progress in genetics of both common and rare respiratory diseases in a comprehensive fashion (Chapters 9 to 18).We have used a broad definition of "genetics."One might ask: Why are animal models discussed so prominently? What does X-ray crystallography have to do with genetics? We contend that genetics is not limited to the study of rare monogenic disorders, and that genetic investigation does not end with the identification of significant genetic association. Essentially every pulmonary disease has some degree of genetic determination and many have significant interaction with key environmental factors. We wish to show how genetic methods will change the research practices of pulmonologists and demonstrate that genetic research can and should lead to the understanding of molecular mechanisms of disease and functional effects of genetic variation. This requires both genomic physiology in animals (Chapter 7) and functional genomic studies of in vitro systems (Chapter 6).

We have attempted to demonstrate the links between rare monogenic disorders and more common complex diseases by including discussions of epidemiology, natural history, monogenic syndromes, complex disease components, and animal models within each of our disease-specific chapters. Genetic nomenclature is often not standardized, but we have tried to refer to the HUGO symbols for human genes that are discussed in each chapter. Other aspects of nomenclature remain non-uniform; for example, although many geneticists prefer "Marfan syndrome" to "Marfan's syndrome," the possessive form remains in widespread use for genetic syndromes in the medical literature, and we have left these decisions to the authors of each chapter.

We hope that this book will be useful for pulmonary researchers, both students at the beginning of their careers and experienced investigators who are well established.We are particularly hopeful that those at the beginning of their investigative careers will turn to genetics as a way forward to understanding respiratory diseases and that this book will help them in this task. We also hope that clinicians, both pulmonologists and medical geneticists,will find useful reference information as well; although genetics does not yet influence treatment of most of the conditions discussed, it often does influence our understanding of disease pathophysiology. As progress continues, we expect that genetic insights will lead to additional treatment options and pharmacogenetic insights into treatment responses and adverse events. This is already beginning in asthma (Chapter 8).

As in any multi-author book, the success of the endeavor relates to the commitment and creativity of the collaborating authors; we are extremely thankful for the hard and careful work of each of our contributors. They represent an important resource as we enter the genetic and genomic era of pulmonary medicine. We would also like to thank our colleagues at Hodder Arnold who provided outstanding support for this project, including Joanna Koster, Naomi Wilkinson, Sarah Burrows, Carole Goodall, Heather Smith, and Alyson Thomas. Finally,we must thank our families for their support, their patience, and their love during this long and arduous project: Rachel, Anna, and Andrew; Nicole, Calli, Tess, and Skylar; Judith, Tim, James, and Ben; and Debby, Ben, and Matthew.