DOCSLIB.ORG

Mendel and Modern Genetics: the Legacy for Today

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mendel and Modern Genetics: the Legacy for Today Review Endeavour Vol.27 No.2 June 2003 63 Mendel and modern genetics: the legacy for today Garland E. Allen Department of Biology, Washington University, St Louis, MO 63130, USA The legacy of Mendel’s pioneering studies of hybridiz- offered for his breeding data seemed reminiscent of so ation in the pea continues to influence the way we many of the speculative, particulate theories of heredity understand modern genetics. But what sort of picture that had abounded in the post-Darwinian era, including did Mendel himself have of his work and its ultimate Darwin’s own ‘provisional hypothesis of pangenesis’, uses, and how does that picture compare with the col- August Weismannn’s elaborate theory of ‘ids, idants and lection of ideas and methodologies that was put for- biophors’, Ernst Haeckel’s imaginary ‘plastidules’, and ward in his name and later became known as Hugo de Vries’ postulated ‘pangenes’. Consequently, to ‘Mendelism’? With genetics standing at the center of some, at least, Mendel’s work seemed like just one more of our present biomedical and biotechnological research, the sort of abstract proposals they had encountered all too an examination of the history of our concepts in the frequently. In point of fact the paper probably seemed field can help us better understand what we should and extraordinarily dense, with no illustrations but numerous should not expect from current genetic claims. For that binomial expansions, which were likely to have been a put- enterprise there is no better starting place than Mendel off for many biologists who at the time were notoriously himself. math-shy. For whatever reason, for the first decade of its re-emergence into the scientific world, Mendel’s contri- As we celebrate 50 years of the Watson–Crick model of bution remained controversial at best, dismissed by DNA, it is worth stepping back to take a longer look at the significant sections of the biological community at worst. work that started it all: the pioneering hybridization What ultimately served to establish Mendelism on more studies of the pea (Pisum sativum) and bean (Phaesolus) firm ground between 1900 and 1915 was: (1) its extension by Gregor Johann Mendel (1822–1884) (Fig. 1). Although to an increasingly wide variety of organisms; and (2) its Mendel’s work was first presented at a meeting of the unification with the cytological work on chromosomes Bru¨ nn Natural History Society in 1865, and published in carried out principally through the work of Thomas Hunt its Proceedings in 1866, it received only a modicum of Morgan (1866–1945) and his young, enthusiastic team of attention until 1900, when it was more or less simul- investigators at Columbia University between 1911 and taneously rediscovered by three different investigators: 1925. The work of the Morgan school demonstrated that Carl Correns (1864–1933) in Germany, Hugo De Vries the abstract elements or ‘factors’ discussed by early 20th- (1848–1935) in the Netherlands, and Erich von Tscher- century Mendelians could be regarded as discrete, mak-Szeneygg (1871–1962) in Austria. Whilst all three material units arranged linearly along the chromosomes, found Mendel’s work suggestive, it is not clear that any of them really saw the significance of what he had done, and none of the ‘rediscoverers’ became a major promoter of the new genetics [1]. The first major publicist for Mendel’s work was William Bateson (1865–1926) in England. Through the Royal Horticultural Society, Bateson had Mendel’s paper trans- lated into English for the first time, and wrote a general exposition that laid out the basic principles of what soon came to be known as ‘Mendelism’ [2]. Bateson’s work brought Mendel to the attention of numerous workers in England, Scandinavia and the United States, in particular to many of those involved in practical animal and plant breeding [3]. Although there was reluctance in some quarters to embrace Mendel’s work immediately – Fig. 1. Gregor Johann Mendel (standing, second from right) with members of the especially among academic biologists – by the end of the Augustinian monastery of StThomas in Brno in about 1862. Mendel can be seen first decade of the 20th century, the theory had gained a observing a plant specimen. Others in the photograph of particular importance in Mendel’s life are the Abbot Cyrill Napp (seated, second from right) and Matous considerable following. However, the explanation Mendel Kla´ cel (seated, first from right), who was also interested in natural science and philosophy, and with whom Mendel had frequent lively discussions. Reproduced, Corresponding author: Garland E. Allen ([email protected]). with permission, from [5], p. 212. http://ende.trends.com 0160-9327/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0160-9327(03)00065-6 64 Review Endeavour Vol.27 No.2 June 2003 the sort of picture Mendel himself envisaged. Second, as an Box 1. The common picture of Mendelian theory introduction to the study of genetics, it has led to † Mendel observed the inheritance patterns of traits or character- unfortunate and now long-entrenched misunderstandings istics in pea plants, such as height, pod color and or seed shape, of how genes really function, and the relationship between each of which showed alternate forms: tall/short, yellow/green genes and the development of adult traits that has carried and smooth/wrinkled, respectively. over into molecular genetics. † Mendel referred to these alternate conditions as dominant and recessive. † Mendel hypothesized that each trait was represented in the germ Mendel’s background cells of adult plants by two determinants (referred to in his paper Mendel was born on 22 July 1822, in the small rural village as ‘Anlagen’ or ‘elements’), one received from each parent; these of Hyncice, in Moravian Silesia, then part of the Austro– determinants were symbolized by Mendel with a capital letter for Hungarian Empire. As the only son of a peasant farmer, he the dominant form (e.g. A) and a lower-case letter for the recessive was expected to follow in his father’s footsteps and take up form (e.g. a). † The determinants could be combined in one of three ways: two farming. But early on, his interest in natural history and dominants (AA), two recessives (aa) or a dominant and a his studious ways brought him to the attention of the recessive, or hybrid (Aa). priest, Friar Schreiber and the local schoolteacher. In spite † Although he knew nothing about the cytology of chromosomes, of financial hardship for his family, young Johann was sent Mendel hypothesized that in the formation of the pollen or egg cell, the two factors for each trait would separate and go into to a larger school in a nearby village and eventually different gametes; thus a parent that was pure dominant would qualified for Gymnasium in Opava (Troppau). It was a produce gametes all of which contained the dominant factor (A), period of extreme privation, but Mendel managed to and a parent that was pure recessive would produce gametes all of graduate in 1840 with considerable academic success. One which contained the recessive factor (a); hybrid parents, however, of the chief influences on him at the time were Schreiber’s would produce two kinds of gametes: 50% would contain the dominant factor (A) and 50% the recessive factor (a). Enlightenment ideals, particularly his emphasis on † At fertilization, the double-determinant condition would be science as a way of dispelling superstition and ignorance. restored. Schreiber was keenly interested in applying scientific † If both parents were hybrids, any of the three possible combi- principles to improve humanity, and was heavily involved nations could occur and would be distributed randomly, accord- with local agricultural groups and the Pomological ing to the laws of probability: 1 AA:2Aa: 1 aa; because organisms that are Aa and AA look alike, the ratio based on appearance of the Society [5]. traits (what later came to be called ‘phenotype’) would be 3:1. Financial problems continued to plague Mendel as he † When two or more characteristics (e.g. Aa, Tt) are followed in a tried to continue his studies at the Philosophy Institute in dihybrid cross, the two sets of determinants segregate randomly, Olomuc (Olmu¨ tz). After several periods of illness, brought so that any combination of A, a, T and t is possible, what came to be on it is thought by his poverty and overwork, Mendel known as the principle of random assortment. † Factors somehow determine traits, so that after the term ‘gene’ managed to finish his studies at the Institute and entered was introduced in 1909, it was common to speak of a ‘gene for Olomuc University. Here, according to records, he took a tallness’ or a ‘gene for wrinkled seed’. During the early years of the course of lectures in physics, mathematics and logic. Mendelian theory, this was referred to as the ‘unit–character’ However, unable to complete his degree owing to financial hypothesis. † Factors are not modified by being combined with their alternate constraints, he applied for, and was accepted into, the form; thus, the factor, t, for shortness is not affected in any way by Augustinian monastery of St Thomas at Brno (then being combined with the dominant factor, T, for tallness in the Bru¨ nn), Moravia in 1843 (Fig. 2). Although he did not hybrid, a concept that became known as the concept of the ‘purity feel a particularly fervent spiritual calling, Mendel of the gametes’. realized shortly after joining the monastery that at last he was free from constant financial worries and could pursue his intellectual interests in exchange for attending and that observed variations in the patterns of inheritance to pastoral duties.
Load more

Recommended publications
  • The Early History of Medical Genetics in Canada William Leeming OCAD University [email protected]
    OCAD University Open Research Repository Faculty of Liberal Arts & Sciences and School of Interdisciplinary Studies 2004 The Early History of Medical Genetics in Canada William Leeming OCAD University [email protected] © Oxford University Press. This is the author's version of the work. It is posted here for your personal use. Not for redistribution. Original source at DOI: 10.1093/shm/17.3.481. Recommended citation: Leeming, W. “The Early History of Medical Genetics in Canada.” Social History of Medicine 17.3 (2004): 481–500. Web. Leeming, W. (2004). The early history of medical genetics in Canada. Social History of Medicine, 17(3), 481-500. Pre-Publication Draft The Early History of Medical Genetics in Canada Abstract: This article shows that the intellectual and specialist movements that supported the growth of medical genetics in Canada between 1947 and 1990 were emergent phenomena, created, split, and reattached to different groups of actors, and reconfigured numerous times over the course of four decades. In each instance, new kinds of working relationships appeared; sets of diverse actors in local university- hospital settings coalesced into a new collectivity; and, as a collectivity, actors defined and/or redefined occupational roles and work rules. In its beginnings, medical genetics appears to be the object of a serious institutional manoeuver: a movement in support of the creation of examining and teaching positions in human genetics in North American medical schools. With time, the institutionalization of ‘medical genetics’ took hold, spurred on by changes in the rate and direction of service delivery associated with genetic consultation and laboratory services in clinical settings.
    [Show full text]
  • Part I April 1952
    HEREDITY VOLUME 6 PART I APRIL 1952 STATISTICALMETHODS IN GENETICS R. A. FISHER Being the Bateson Lecture delivered at the John lnnes Horticultural Institution on Friday, 6th July 1951 * THEtitle chosen for this lecture is "StatisticalMethods in Genetics," but after hearing what I have written you may think that it is not so much an account of the contributions which the study of Statistics has made to the advance of Genetics, as an examination of the nature of genetical Science from the point of view of a statistician,. My reason for taking this point of view is that for many active years of my life I was fully engaged in doing what I could to further the progress of statistical methods, and that though for 25 years or so I have enjoyed the excitements of genetic experimentation, Genetics has only gradually come to be, for me, a whole time study, in place of a very fascinating hobby. Since that experience is in itself exceptional, it may be that the refiexions gathered on the way are worthy of record, and of interest to my genetical colleagues. Genetics and Statistics have in common that they are both characteristic products of the twentieth century. As we should recognise them now, neither of them existed before the year 1900. Of course I do not ignore the fact that earlier workers of many nations, Naudin and Godron, for example, Knight, Gaertner and Kohlreuter broached the practical problems of experimentation in heredity, or that on the theoretical side Galton and Weismann put forward speculations sometimes to an interesting extent near the truth.
    [Show full text]
  • Elements of Genetics
    GENETICS AND PLANT BREEDING Elements of Genetics Dr. B. M. Prasanna National Fellow Division of Genetics Indian Agricultural Research Institute New Delhi-110012 (12-06- 2007) CONTENTS Introduction History Cell Cell Division Special Chromosomes Dominance Relationships Gene Interactions Multiple Alleles Sex Determination Sex Linkage Linkage and Crossing Over Genetic Mapping Structural Changes in Chromosomes Numerical Changes in Chromosomes Nature of the Genetic Material Gene Regulation Operon Concept Gene Concept Mutation Polygenic and Quantitative Inheritance Extrachromosomal Inheritance Plant Tissue Culture Keywords Mitosis, Meiosis 1 Introduction In biology, heredity is the passing on of characteristics from one generation to the next. It is the reason why offspring look like their parents. It also explains why cats always give birth to kittens and never puppies. The process of heredity occurs among all living organisms, including animals, plants, bacteria, protists and fungi. Genetic variation refers to the variation in a population or species. Genetics is the study of heredity and variation in living organisms. Two research approaches were historically important in helping investigators understand the biological basis of heredity. The first of these approaches, ‘transmission genetics’, involved crossing organisms and studying the offsprings' traits to develop hypotheses about the mechanisms of inheritance. The second approach involved using cytological techniques to study the machinery and processes of cellular reproduction. This approach laid a solid foundation for the more conceptual understanding of inheritance that developed as a result of transmission genetics. Ever since 1970s, with the advent of molecular tools and techniques, geneticists are able to intensively analyze genetic basis of trait variation in various organisms, including plants, animals and humans.
    [Show full text]
  • A Brief History of Genetics
    A Brief History of Genetics A Brief History of Genetics By Chris Rider A Brief History of Genetics By Chris Rider This book first published 2020 Cambridge Scholars Publishing Lady Stephenson Library, Newcastle upon Tyne, NE6 2PA, UK British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Copyright © 2020 by Chris Rider All rights for this book reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owner. ISBN (10): 1-5275-5885-1 ISBN (13): 978-1-5275-5885-4 Cover A cartoon of the double-stranded helix structure of DNA overlies the sequence of the gene encoding the A protein chain of human haemoglobin. Top left is a portrait of Gregor Mendel, the founding father of genetics, and bottom right is a portrait of Thomas Hunt Morgan, the first winner of a Nobel Prize for genetics. To my wife for her many years of love, support, patience and sound advice TABLE OF CONTENTS List of Figures.......................................................................................... viii List of Text Boxes and Tables .................................................................... x Foreword .................................................................................................. xi Acknowledgements ................................................................................. xiii Chapter 1 ...................................................................................................
    [Show full text]
  • The Third Base
    Appendix The Third Base Donald Forsdyke If I thought that by learning more and more I should ever arrive at the knowledge of absolute truth, I would leave off studying. But I believe I am pretty safe. Samuel Butler, Notebooks Darwin’s mentor, the geologist Charles Lyell, and Darwin himself, both con- sidered the relationship between the evolution of biological species and the evolution of languages [1]. But neither took the subject to the deep informa- tional level of Butler and Hering. In the twentieth century the emergence of a new science – Evolutionary Bioinformatics (EB) – was heralded by two dis- coveries. First, that DNA – a linear polymer of four base units – was the chromosomal component conveying hereditary information. Second, that much of this information was “a phenomenon of arrangement” – determined by the sequence of the four bases. We conclude with a brief sketch of the new work as it relates to William Bateson’s evolutionary ideas. However, imbued with true Batesonian caution (“I will believe when I must”), it is relegated to an Appendix to indicate its provisional nature. Modern languages have similarities that indicate branching evolution from common ancestral languages [2]. We recognize early variations within a language as dialects or accents. When accents are incompatible, communi- cation is impaired. As accents get more disparate, mutual comprehension de- creases and at some point, when comprehension is largely lost, we declare that there are two languages where there was initially one. The origin of lan- guage begins with differences in accent. If we understand how differences in accent arise, then we may come to understand something fundamental about the origin of language (and hence of a text written in that language).
    [Show full text]
  • Statement About Pnas Paper “The New Mutation Theory of Phenotypic Evolution”
    July 30, 2007 (revised) Brief Historical Perspectives of the Paper “THE NEW MUTATION THEORY OF PHENOTYPIC EVOLUTION” Proceedings of the National Academy of Sciences, USA, 104:12235-12242, Published July 17, 2007 online. Masatoshi Nei The following is the author’s account of the history of development of the mutation theory of phenotypic evolution and related matters. Darwinism (1) Charles Darwin proposed that evolution occurs by natural selection in the presence of fluctuating variation. (2) At his time, the mechanism of generation of new variation was not known, and he assumed that new variation is generated by climatic changes, inheritance of acquired characters, spontaneous variations, etc. However, he believed that new variation occurs in random direction and evolutionary change is caused by natural selection. (3) He assumed that enormous phenotypic diversity among different phyla and classes is the result of accumulation of gradual evolution by natural selection. Saltationism Several biologists such as Thomas Huxley, William Bateson, and Hugo de Vries argued that the extent of variation between species is much greater than that within 1 species and therefore saltational or macromutational change is necessary to form new species rather than gradual evolution as proposed by Darwin. In this view a new species can be produced by a single macromutation, and therefore natural selection is unimportant. This view was strengthened when de Vries discovered several new forms of evening primroses which were very different from the parental species (Oenothera lamarckiana) and appeared to be new species. This discovery suggested that new species can arise by a single step of macromutation. However, it was later shown that O.
    [Show full text]
  • Chromosomes in the Clinic: the Visual Localization and Analysis of Genetic Disease in the Human Genome
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2013 Chromosomes in the Clinic: The Visual Localization and Analysis of Genetic Disease in the Human Genome Andrew Joseph Hogan University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the History of Science, Technology, and Medicine Commons Recommended Citation Hogan, Andrew Joseph, "Chromosomes in the Clinic: The Visual Localization and Analysis of Genetic Disease in the Human Genome" (2013). Publicly Accessible Penn Dissertations. 873. https://repository.upenn.edu/edissertations/873 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/873 For more information, please contact [email protected]. Chromosomes in the Clinic: The Visual Localization and Analysis of Genetic Disease in the Human Genome Abstract This dissertation examines the visual cultures of postwar biomedicine, with a particular focus on how various techniques, conventions, and professional norms have shaped the `look', classification, diagnosis, and understanding of genetic diseases. Many scholars have previously highlighted the `informational' approaches of postwar genetics, which treat the human genome as an expansive data set comprised of three billion DNA nucleotides. Since the 1950s however, clinicians and genetics researchers have largely interacted with the human genome at the microscopically visible level of chromosomes. Mindful of this, my dissertation examines
    [Show full text]
  • INTRODUCTION to GENETICS Table of Contents Heredity, Historical
    INTRODUCTION TO GENETICS Table of Contents Heredity, historical perspectives | The Monk and his peas | Principle of segregation Dihybrid Crosses | Mutations | Genetic Terms | Links Heredity, Historical Perspective | Back to Top For much of human history people were unaware of the scientific details of how babies were conceived and how heredity worked. Clearly they were conceived, and clearly there was some hereditary connection between parents and children, but the mechanisms were not readily apparent. The Greek philosophers had a variety of ideas: Theophrastus proposed that male flowers caused female flowers to ripen; Hippocrates speculated that "seeds" were produced by various body parts and transmitted to offspring at the time of conception, and Aristotle thought that male and female semen mixed at conception. Aeschylus, in 458 BC, proposed the male as the parent, with the female as a "nurse for the young life sown within her". During the 1700s, Dutch microscopist Anton van Leeuwenhoek (1632-1723) discovered "animalcules" in the sperm of humans and other animals. Some scientists speculated they saw a "little man" (homunculus) inside each sperm. These scientists formed a school of thought known as the "spermists". They contended the only contributions of the female to the next generation were the womb in which the homunculus grew, and prenatal influences of the womb. An opposing school of thought, the ovists, believed that the future human was in the egg, and that sperm merely stimulated the growth of the egg. Ovists thought women carried eggs containing boy and girl children, and that the gender of the offspring was determined well before conception.
    [Show full text]
  • Doctorates Awarded in America in Botany and Zoology More Than Doubled
    DIVISION OF THE HUMANITIES AND SOCIAL SCIENCES CALIFORNIA INSTITUTE OF TECHNOLOGY PASADENA, CALIFORNIA 91125 GENETICS IN THE UNITED STATES AND GREAT BRITAIN 1890 to 1930: QUERIES AND SPECULATIONS Daniel J. Kev1es HUMANITIES WORKING PAPER 15 December 1978 According to recent scholarship in the early history of genetics, by the l890s many younger biologists were growing restless with phylogenetic morphology and embryology, the traditional descriptive approaches to the much-debated problems of evolutionary theory. Eager to break away from these approaches, a number of these biologists -- and some older ones such as Alfred R. Wallace called for programs of experimental research in evolution addressed in particular to the problems of heredity and variation. "No problems in the whole range of biology," Charles O. Whitman of Woods Hole typically said, were of 1 "higher scientific interest or deeper practical import to humanity." In England Francis Galton inspired one of the more important experimental research programs -- W. F. R. Weldon's statistical analyses, developed in collaboration with Karl Pearson, of variations in large populations. Another important departure was the program of hybridization experiments exemplified in the research of William Bateson. Pearson and Weldon helped establish the field of heredity studies known as biometry. The research of Bateson and others paved the way for the rediscovery in 2 1900 and then vigorous advocacy of the Mendelian paradigm. Mendel's ideas did not gain rapid acceptance in all biological quarters in either the United States or Great Britain, In England, the biometricians Weldon and Pearson hotly disputed the validity of Mendel's results, the merits of his conceptual scheme, and even the integrity of his British advocates, especially Bateson.
    [Show full text]
  • William Bateson: Scientific Correspondence and Papers (MS Add.8634)
    Cambridge University Library, Department of Archives and Modern Manuscripts Finding Aid - William Bateson: Scientific Correspondence and Papers (MS Add.8634) Generated by Access to Memory (AtoM) 2.4.0 Printed: February 27, 2019 Language of description: English Cambridge University Library, Department of Archives and Modern Manuscripts https://archive.lib.cam.ac.uk/index.php/william-bateson-scientific-correspondence-and-papers William Bateson: Scientific Correspondence and Papers Table of contents Summary information .................................................................................................................................... 20 Administrative history / Biographical sketch ................................................................................................ 20 Scope and content ......................................................................................................................................... 20 Notes .............................................................................................................................................................. 21 Access points ................................................................................................................................................. 21 Collection holdings ........................................................................................................................................ 22 MS Add.8634/A.1-A.84, Biographical papers (c.1859-1935 & 1972) .....................................................
    [Show full text]
  • Mendel's Opposition to Evolution and to Darwin
    Mendel's Opposition to Evolution and to Darwin B. E. Bishop Although the past decade or so has seen a resurgence of interest in Mendel's role in the origin of genetic theory, only one writer, L. A. Callender (1988), has concluded that Mendel was opposed to evolution. Yet careful scrutiny of Mendel's Pisum pa- per, published in 1866, and of the time and circumstances in which it appeared suggests not only that It Is antievolutlonary In content, but also that it was specif- ically written in contradiction of Darwin's book The Origin of Species, published in 1859, and that Mendel's and Darwin's theories, the two theories which were united in the 1940s to form the modern synthesis, are completely antithetical. Mendel does not mention Darwin in his Pi- [Mendel] in so far as they bore on his anal- sum paper (although he does in his letters ysis of the evolutionary role of hybrids." to Nlgeli, the famous Swiss botanist with Olby's (1979) article, entitled "Mendel whom he initiated a correspondence, and No Mendelian?," led to a number of revi- in his Hieracium paper, published In 1870), sionist views of Mendel's work and his in- but he states unambiguously in his intro- tentions, although no agreement has been duction that his objective is to contribute reached. For instance, some writers, un- to the evolution controversy raging at the like de Beer, Olby, and Callender, overlook time: "It requires a good deal of courage or minimize the evolutionary significance indeed to undertake such a far-reaching of Mendel's paper, while others maintain task; however, this seems to be the one that Mendel had little or no interest in he- correct way of finally reaching the solu- redity, an interpretation that has been op- tion to a question whose significance for posed by Hartl and Orel (1992): "We con- the evolutionary history of organic forms clude that Mendel understood very clearly must not be underestimated" (Mendel what his experiments meant for heredity." 1866).
    [Show full text]
  • Microdissection and Molecular Cloning of Extra Small Ring Chromosomes Of
    'r¡o "to. Q8 MICRODISSECTION AND MOLECULAR CLONING oFEXTRASMALLRINGCHROMOSOMESoF HUMAN by Yu-Yan Fang (MBBS) Thesis submitted for the degree of Doctor of PhilosoPhY I)epartment of Paediatrics School of Medicine The University of Adelaide Australia January, 1998 t: i.t Errata for Thesis of Yu-Yan Fang Pnge 6,line 5-6 delete "ancl they are chromosome." Pngc 79, Parngrnph 2 replace " 0.65-7.5ol,ro wit\ " 0.065-0.75%" replace " 0 .'1, -0 .7 2ol,¡o with " 0.07 -0.07 2yo " replace " 6"/rro with 0.6%" Pnge 55, Pnrngrøph 2,line 6 replace "since they also mapped to CY720" with the phrase "sir-ì.ce they mapped to C{770 but not CY120" Pnge 55, Pnragrnph 2, line 10 replace "The other three clones (y42,Y73 and Y87) were negative for CY120 ..." with "The other three clones were positive for CY120 and CYI70 (Fig. Z-4). .." Pnge 56,line 6-7 replace "cosmid 776F7" with "cosmid177C6" Pnge 56,line 10 repiace "cosmid 177C6" with "cosmid176F1" Pnge 57,Tnble 3-3 In this table replace the cosmids labelled 177C6 and176F1with176F1 and 177C6 lespectively. Fig.3-6 At pter, replace "177C6" witln"176F1" At 4q12, replace "\76F1." with"177C6" Pnge 65,Iine 2 replace "FIis" with "F{er" Fig.4-10 replace "devision" with "division" Pnge 73, line 7 replace "since FISH study showed ..." with "since FISH study with the probe in the region of LScen-+qllclearly showed defined euchromatic region between the two FISH signals, and on the basis of the abnormal phenotype in this patient it is also suggested that the PWS/AS region was involved in this marker." u TABLE OF CONTEI\TS Chapter 1 Intrõduction and literature review.
    [Show full text]