Emery and Rimoin's Principles and Practice of Medical Genetics (eBook)

Bruce Korf, Reed E. Pyeritz, David L. Rimoin (Herausgeber)

eBook Download: PDF | EPUB

2013 | 6. Auflage
4700 Seiten
Elsevier Science (Verlag)
978-0-12-383835-3 (ISBN)

Infos

For decades, Emery and Rimoin's Principles and Practice of Medical Genetics has provided the ultimate source for practicing clinicians to learn how the study of genetics can be integrated into practice. With almost 5,000 pages of detailed coverage, this fully online sixth edition of the classic reference adds the latest information on prenatal diagnosis, genetic screening, genetic counseling, and treatment strategies to complete its coverage of the growing field for medical students, residents and physicians involved in the care of patients with genetic conditions. Clinically oriented information is supported by expanded sections on basic principles of genetics, research approaches, and analytics to embrace the evolving population of students, researchers, and practitioners who are integrating their work to provide advanced diagnosis, prevention and treatment of human disease. With advances in high-throughput technologies propelling the closer integration of lab and clinical work, this edition bridges the gap between high-level molecular genetics and clinical application. - Features 174 review-length contributions that encompass traditional and new areas of the field - including in cancer genetics, genomic technologies, and molecular assays - Provides many thousands of pertinent literature references guiding the reader in identifying related topics - Fully illustrated with hundreds of color images, supporting identification, concept illustration and method processing

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Chapter 1

History of Medical Genetics

Victor A. McKusick∗, Formerly University Professor of Medical Genetics, Johns Hopkins University, Physician, Johns Hopkins Hospital, Baltimore, MD, USA

Peter S. Harper, Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, UK

This article is a revision of the previous edition article by Victor A McKusick, volume 1, pp 3–32, © 2007, Elsevier Ltd.

1.1 Preface (Peter Harper)

Victor McKusick’s chapter “History of Medical Genetics,” which first appeared in the third edition of this textbook in 1996, has provided readers with a masterly account of the origins and development of the field, containing a remarkable amount of information in the limited space available. This has been a historical account as seen by somebody who has lived through most of it, and who has perhaps shaped the development of medical genetics more than any other individual. While this may at times have given a personal slant to the areas emphasized, it provides an unrivaled perspective on the field—indeed for many years it has been the only substantive account, no detailed history of medical genetics having appeared until recently (Harper, 2008).

McKusick’s death in 2008 has sadly removed the possibility of him providing a revised edition of his chapter, but his continued active attention to, and involvement in, the detailed evolution of medical genetics, up to the very end of his life, seen particularly in his interest in the Human Genome Project (HGP) and in the updating of his catalog OMIM, not to mention his many unique photographs, means that the chapter is still of the greatest value, and that it would be wrong, as well as regrettable, were it to be discarded. At the same time though, the highly condensed nature of the text makes it difficult, if not impossible to edit without making radical changes.

Thus, for the present edition of this book, a compromise has been reached, whereby the chapter remains essentially intact, but is framed by this introduction and by a postscript outlining some of the relevant topics that the original chapter does not cover. The web-based format of this new edition will allow the chapter to evolve progressively over the coming years, in keeping with changes in the field, which have not only seen continuing new advances, but have also shown the urgent need for the history of its recent past to be recorded and preserved.

1.2 Introduction

Medical genetics is the science of human biologic variation as it relates to health and disease. Clinical genetics is that part of medical genetics concerned with the health of individual humans and their families. Alternatively, clinical genetics can be defined as the science and practice of diagnosis, prevention, and management of genetic disorders.

Within recent years, medical genetics has become established as a clinical specialty, as the culmination of developments that began in 1956 with the description of the correct chromosome number of the human. With the discovery of specific microscopically visible chromosomal changes associated with clinical disorders, beginning with Down syndrome in January 1959, medical genetics acquired an anatomic base. Medical geneticists now had their specific organ—the genome—just as cardiologists had the heart and neurologists had the nervous system.

The anatomic base of medical genetics was greatly extended with the mapping of genes to chromosomes and specific chromosomal regions, at an ever-accelerating pace, during the past 30 years. Gene mapping has not only enlarged the base for medical genetics but, indeed, as pointed out to me by Charles Scriver (personal communication, 1980), has also provided a neo-Vesalian basis for all of medicine (1). Medical historians tell us that the anatomy of Vesalius published in 1543 was of pivotal importance in the development of modern medicine. It was the basis of the physiology of William Harvey (1628) and the morbid anatomy of Morgagni (1761). Similarly, human gene mapping constitutes an approach to the study of abnormal gene function in all diseases; the gene mapping approach has been adopted by researchers in almost all branches of medicine in the study of their most puzzling disorders. Through mapping, they have sought the basic defect in these disorders, and their clinical colleagues have used mapping information for diagnosis and carrier detection. The ultimate anatomic basis for medical genetics, the DNA sequence, is provided by the HGP.

In this brief history of medical genetics, I trace the foundations of the field that were laid between 1865, when Mendel published his work, and 1956, when the correct chromosome number was reported. I then discuss the events of the past 50 years that have seen the main evolution of the discipline. Finally, I attempt some projections for the future.

1.3 Foundations of Medical Genetics Before 1956

Medical genetics in many developed countries is now a recognized specialty. In the United States, for example, the American Board of Medical Genetics certifies practitioners in the field, including PhD medical geneticists; in 1991, the American Board of Medical Genetics became the 24th organization to join the family of certifying American specialty boards. Medical genetics is a rather unusual branch of clinical medicine; indeed, it may be nearly unique in that it originated out of a basic science. Most specialties started as crafts (or out of a technological advance such as radiography) and only subsequently acquired basic science foundations.

The basic science that developed before 1956 and served as the foundation for the developments of the past 50 years included Mendelism, cytogenetics, biochemical genetics, immunogenetics, and statistical, formal, and population genetics.

1.3.1 Mendelism

The demonstration of the particulate nature of inheritance was the contribution of Gregor Mendel (1822–1884), a monk and later Abbot in an Augustinian monastery (Figure 1-1) in Brünn (now Brno), Moravia (now the Czech Republic). The terms dominant and recessive were his. The delay in recognition of his work has been attributed to various factors, but the most likely is poor timing; in 1865, when Mendel reported his findings and conclusions, the chromosomes had not yet been discovered. Because its physical basis, meiosis, had not yet been described, Mendelism had no plausible basis to qualify it over other possible mechanisms of inheritance such as blending inheritance, which was favored by Francis Galton (1822–1911) another of Mendel’s contemporaries (151).

FIGURE 1-1 (a) Mendel’s monastery as it appeared in 1971. (b) Participants in the 2005 International Workshop on Genetics, Medicine and History, held of Mendel’s Abbey, Brno.

R. A. Fisher (1890–1962) (2) raised a question whether Mendel’s results were “too good”; that is, the data agreed too closely with the conclusions (see the discussion of this matter by Novitski (3)). (Mendel’s “round” [R] versus “wrinkled” [r] trait in the garden pea has been shown to be due to a transposon insertion in the R gene for a starch-branching enzyme. The wrinkled state is due to lack of an osmotic effect present when the normally functioning enzyme is present. The first demonstration of mutation in the human due to insertion of a transposon was provided by the Kazazian group (4): a movable element from chromosome 22 was inserted into the factor VIII gene causing hemophilia A.)

Human chromosomes, visualized in tumor cells in mitosis, were pictured in a paper by Walther Flemming (Figure 1-2A), professor of anatomy in Kiel, in 1882 (Figure 1-2B). The term chromosome was introduced by Waldeyer in 1888. Mitosis and meiosis were described in the last quarter of the nineteenth century. (The term meiosis was introduced in 1905 by Farmer and Moore; the process had been previously referred to as the reduction divisions. The word meiosis, usually taken to mean “reduction in size of the pupil,” is from the same root. It is fortunate that the words are spelled differently in the two usages. In fact, Farmer and Moore spelled it “maiosis.” They wrote as follows: “We propose to apply the terms Maiosis or Maiotic phase to cover the whole series of nuclear changes included in the two divisions that were designated as Heterotype and Homotype by Flemming.”)

FIGURE 1-2 A, Walther Flemming (1843–1905), discoverer of chromosomes (152). B, First illustration of human chromosomes, by Flemming (1882) (courtesy of the Genetics and Medicine Historical Network).

During the 1880s, Roux, deVries, and Weismann developed the theory that the chromosomes carry determinants of heredity and development. The state of cytogenetics before the discovery of Mendel’s work was reviewed by E. B. Wilson (Figure 1-3) in his classic text (5). In a discussion of the Roux–deVries–Weismann theory (pp. 182–185), Wilson (5) wrote that “the chromatin is a congeries or colony of invisible self-propagating vital units …, each of which has the power of determining the development of a particular quality. Weismann conceives these units … [to be] associated in linear groups to form the … chromosomes.”

FIGURE 1-3 E. B. Wilson...

Produkt-Details

• Erscheint lt. Verlag: 20.3.2013
• Sprache: englisch
• Themenwelt: Studium ► 2. Studienabschnitt (Klinik) ► Humangenetik
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Technik
• ISBN-10: 0-12-383835-5 / 0123838355
• ISBN-13: 978-0-12-383835-3 / 9780123838353