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CONTRIBUTORS TO THIS VOLUME
Matteo AdinolfiDivision ofMedical &Molecular GeneticsUnited Medical and Dental SchoolsGuy's and St. Thomas's HospitalsLondon Bridge, London, England
John CrollaWessex Regional Genetics LaboratorySalisbury District HospitalSalisbury, Wiltshire, England
Harry C. DietzDepanments ofPediatrics, Medicine,and Molecular Biology and GeneticsJohns Hopkins School ofMedicineBaltimore, Maryland
Regen DrouinResearch Unit inHuman andMolecular GeneticsSaint Francis ofAssisi HospitalResearch CenterLaval University, Montreal, Quebec, Canada
Vincent J.Hearing, Jr.Laboratory ofCell BiologyNational Cancer InstituteNational Institutes ofHealthBethesda, Maryland
Gerald P. HolmquistDivision ofBiologyBeckman Research Institute of the City ofHopeDuane, California
James R. LupskiDepanments ofMolecular and HumanGenetics,Pediatrics and Human Genome CenterBaylor College of MedicineHouston, Texas, and Texas Children's HospitalHouston, Texas
Francesco RamirezBrookdale Center for Molecular BiologyMount Sinai School ofMedicineNew York, New York
Claude-Lise RicherDepanmentofAnatomyUniversity ofMontreal,Montreal, Quebec, Canada, andDepartment ofPathology and PediatricResearch CenterSaint Justine Hospital, Montreal, Quebec,Canada
Benjamin B. RcaDepartment ofMolecular and Human GeneticsBaylor College ofMedicineHouston, Texas
Lynn S. SakaiShriners Hospital forCrippled Childrenand Department ofBiochemistryand Molecular BiologyOregon Health Sciences UniversityPortland, Oregon
Richard A. SpritzDepartments ofMedical Genetics andPediatricsUniversity ofWisconsinMadison, Wisconsin
A Continuation Order Plan is available for this series . A continuation order will bring delivery ofeach new volume immediately upon publication. Volumes are billed only upon actual shipment.For further information please contact the publisher.
ADVANCES INHUMAN GENETICS
Edited by
Harry HarrisFormer Harnwel/ Professor ofHuman GeneticsLate of University ofPennsylvania, Philadelphia
and
Kurt HirschhornHerbert H. Lehman Professor and Chairman ofPediatricsMount Sinai School of Medicine of The City Univers ity of New York
22
Springer Science+Business Media, LLC
The Library of Congress catalogued the first volume of this title as follows:
Advances in human genetics. 1New York, PLenum Press, 1970
(1) v. iIIus. 24-cm.Editors: V. 1- H. Harris and K. Hirschhorn.
1. Human genetics-Collected works. I. Harris, Harry, ed. II. Hirschhorn, Kurt,1926- joint ed.
QH431 .A1A32 573.2'1 77-84583
ISBN 978-1-4757-9064-1 ISBN 978-1-4757-9062-7 (eBook)
DOI 10.1007/978-1-4757-9062-7
©1994 Springer Science+Business Media New YorkOriginally published by Plenum Press, New York in 1994.Softcover reprint of the hardcover Ist edition 1994
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted inany form or by any means, electronic, mechanical, photocopying, microfilming,recording, or otherwise, without written permission from the Publisher
HARRY HARRIS, M.D.
September 1919-July 1994
It is with great sadness that I note the passing of my dear friend and co-editor,Harry Harris, M.D. He, more than anyone in the field, was the ultimate symbolof Human Biochemical Genetics. His numerous contributions over the yearsdeveloped and clarified the concept of biochemical polymorphism to demonstrategenetic individuality and uniqueness of all human beings. His careful study of
biochemical variation included, as well , the clarification of a number of inbornerrors of metabolism. In that, he was the natural heir of Garrod , who was one of
his heroes.
I first met Harry when I was a Fellow in Human Genetics and visited him at theLondon Hospital where he had begun his work on electrophoresis andchromatography to demonstrate individual variation in enzymes. I spent twomagnificent Sabbaticals with him, the first at Kings College Medical School andthe second at the Galton Laboratory. These experiences allowed me to appreciate
Harry as one of the truly great minds in the field of Human Genetics .
This series, Advances in Human Genetics, was founded during a discussion withthe late Alan Liss, at that time the Vice President of Plenum Press, during aninformal conversation on a beach in Cape Cod. While Harry, always a skeptic,expressed doubts that we could fill even a single volume, the response of all in thefield led to the 110 contributions in the 22 volumes so far published. This current
volume is dedicated to his memory. It is in his memory that I will continue to workon additional volumes of the series, and I am most gratified that Robert J. Desnick,Ph.D., M.D., Chairman of the Department of Human Genetics at Mount SinaiSchool of Medicine, will join me as the new co-editor in this effort.
-KH
ARTICLES PLANNED FOR FUTURE VOLUMES
Biochemic al Defects in Immunodeficiency • Rochelle HirschhornAdvances in Prenatal Genetic Diagnosis. John C. Hobbins and Maurice J. MahoneyMalformation Syndromes Caused by Single Gene Defects • Judith G. HallGenetic Screening Using the Tay Sachs Model. Michael M. KabackGenetics of Hormone Receptors and Their Abnormalities • Jesse Roth and Simeon I. TaylorTheory and Practice of Gene Mapping, Including Multipoint Linkage Analysis «Eric S. LanderOrganization and Genet ics of Satellite DNA Families in the Human Genome.
Huntington F. WillardPrimary Sex Determination and Its Aberrations in Man • MalcolmA. Ferguson-SmithThe Molecular Genet ics of Polycystic Kidney Disease • Stephen T. ReedersTriplet Amplification • C. Thomas Caskey and Huda Zoghbi
CONTENTS OF EARLIER VOLUMES
VOLUME 1 (1970)Analysis of Pedigree Data • J. H. EdwardsAutoradiography in Human Cytogenetics • Orlando J. MillerGenetics of Immunoglobulins • H. Hugh Fudenberg and Noel E. Wam erHuman Genetics of Membrane Transport with Emphasis on Amino Acids •
Charles R. Scriver and Peter HechtmanGenetics of Disorders of Intestinal Digestion and Absorption • Jean Frezal and Jean Rey
VOLUME 2 (1971)Glucose-6-Phosophate Dehydrogenase • Henry N. KirkmanAlbinism • Carl J. Witkop. Jr.Acatalasemia • Hugo Aebi and Hedi SuterChromosomes and Abortion • D. H. CarrA Biochemical Genet ic View of Human Cell Culture • William J. Mellman
VOLUME 3 (1972)Prenatal Detection of Genetic Disorders • Henry I. NadlerGanglioside Storage Diseases. John S. 0 ' BrienInduced Chromosomal Aberrat ions in Man • Arthur D. BloomLinkage Analys is Using Somatic Cell Hybrids • Frank H. RuddleThe Structure and Function of Chromatin • David E. Comings
VOLUME 4 (1973)Genetic Screen ing • Harvey L LevyHuman Population Structure • Chris Cannings and L. Cavalli -SforzaStatus and Prospects of Research in Hereditary Deafness • Walter E. Nance and
Freeman E. McConnellCongenital Adrenal Hyperplasia • Maria I. New and Lenore S. LevineCytogenet ic Aspects of Human Male Meiosis • Maj Hulten and J. Lindsten
vii
viii Contents of Earlier Volumes
VOLUME 5 (1975)The Chondrodystrophies • David L RimoinNew Techniques in the Study of Human Chromosomes: Methods and Applicat ions •
Bernard Dutrillaux and Jerome LejeuneThe Thalassem ias: Models for Analysis of Quantitative Gene Control • David Kabat and
Robert D. KolerSpontaneous Mutation in Man • FriedrichVogeland RudigerRathenbergGenet ic Screening Legislation • Philip Reilly
VOLUME 6 (1976)Vitamin-Responsive Inherited Metabolic Disorders. Leon E. RosenbergInherited Deficiency of Hypoxanthine-Guanine Phosphoribosyltransferase in X-Linked Uric
Aciduria • J. Edwin SeegmillerHered itary Hemolytic Anemia Due to Enzyme Defects of Glycolysis • Sergio Piomelli and
Laurence CorashPopulation Structure of the Aland Islands, Finland • James H. Mielke, Peter L Workman.
Johan Fellman, and Aldur W. ErikssonPopulation Genetics amd Health Care Delivery : The Quebec Experience • Claude Laberge
VOLUME 7 (1976)Biochemical Genetics of Carbonic Anhydrase • RichardE. Tashian and Nicholas D. CarterHuman Behavior Genetics • Barton Childs, Joan M. Finucci, MalcolmS. Preston, and
Ann E. PulverMammalian X-Chromosome Inactivation • Stanley M. Gartlerand Robert J. AndinoGenetics of the Complement System • ChesterA. Alper and FredS. RosenSelective Systems in Somatic Cell Genetics • Ernest H. Y. Chu and SandraS. Powell
VOLUME 8 (1977)Genetics and Etiology of Human Cancer. Alfred G. Knudson, Jr.Population Genetics Theory in Relation to the Neutralist-Selectionist Controversy.
Warren J. EwensThe Human a-Amylases • A. Donald Merrit and Robert C. KamThe Genetic Aspects of Facial Abnormalities • Robert J. Gorlin and WilliamS. BoggsSome Facts and Fancies Relating to Chromosome Structure in Man • H. J. Evans
VOLUME 9 (1979)Chromosome and Neoplasia • David G. Harndenand A. M. R. TaylorTerminological, Diagnostic Nosological , and Anatomical-Developmental Aspects of
Developmental Defects in Man • John M. Opitz. JiirgenHerrmann, James C. Pettersen.Edward T. Bersu, and Sharon C. Colacino
Human Alphafetoprotein 1956-1978 • Matteo AdinolfiGenetic Mechanisms Contributing to the Expression of the Human Hemoglobin Loci •
William P. Winter. Samir M. Hanash, and Donald L RucknagelGenetic Aspects of Folate Metabolism • Richard W. Erbe
Contents of Earlier Volumes
VOLUME 10 (1980)Biochemi stry and Genetics of the ABO, Lewis, and P Blood Group Systems •
Winifred M. WatkinsHLA- A Central Immunological Agency of Man • D. Bernard Amos and D. D. KostyuLinkage Analysis in Man • P. Michael Conneally and Marian L RivasSister Chromatid Exchanges • Samuel A. Latt, Rhona R. Schreck. Kenneth S. Loveday,
Charlotte P. Dougherty, and Charles F. ShulerGenetic Disorders of Male Sexual Differentiation. Kaye R. Fichman, Barbara R. Mige on,
and Claude J. Migeon
VOLUME 11 (1981)The Pi Polymorphism: Genetic, Biochemical , and Clinical Aspects of Human a -Antitrypsin
• Magne K. Fagerhol and Diane Wilson CoxSegregation Analysis • R. C. ElstonGenetic, Metabolic, and Biochemical Aspects of the Prophyrias • Shigeru Sassa and
Attallah KappasThe Molecular Genetics of Thalassemia • Stuart H. Orkin and David G. NathanAdvances in the Treatment of Inherited Metabolic Diseases • Robert J. Desni ck and
Gregory A. Gravowski
VOLUME 12 ( 1982)Genetic Disorders of Collagen Metaboli sm • David W. Hollister, Peter H. Beyers. and
Karen A. HolbrookAdvances in Genetics in Dermatolog y • Howard P. Baden and Philip A. HookerHaptoglobin: The Evolut ionary Product of Duplication, Unequal Crossing over, and Point
Mutation • Barbara H. Bowman and Alexander KuroskyModels of Human Genetic Disease in Domestic Animals • D. F. Patterson, M. E. Haskins.
and P. F. JezykMapping the Human Genome, Cloned Genes, DNA Polymorphisms, and Inherited Disea.e •
Thomas B. Shows, Alan Y. Sakaguchi. and Susan L Naylor
ix
VOLUME 13 (1983)The Genetics of Blood Coagulation • John B. Graham, Emily S. Barrow. Howard M. Reisner.
and Cora -Jean S. EdgellMarker (Xj-Linked Mental Retardation • Gillian Turner and Patr icia JacobsHuman Antibody Genes: Evolutionary and Molecular Genetic Perspectives •
Jay W. Ellison and Leroy E. HoodMutations Affecting Trace Elements in Humans and Animals : A Genetic Approach to an
Understanding of Trace Elements. D. M. Danks and J. CamakarisPhenylketonuria and Its Variants • Seymour Kaufman
VOLUME 14 (1985)Cytogenetics of Pregnancy Wastage • Andre Boue, Alfred Gropp. and Joelle BoueMuMutation in Human Populations • James F. Crow and Carter DennistonGenetic Mutations Affecting Human Lipoprotein Metabolism • Vassili s I. Zanni s and
Jan L BreslowGlucose -6-Phosphate Dehydrogenase • L Luzzato and G. Banistut zi
x Contents of Earlier Volumes
Steroid Sulfatase Deficiency and the Genetics of the Short Arm of theHuman X Chromosome• Larry J. Shapiro
VOLUME 15 (1986)Chromosomal Abnormalities in Leukemia and Lymphoma: Clinical and Biological
Significance • Michelle M. Le BeauandJanet D. RowleyAn Algorithm for Comparing Two-Dimensional Electrophoretic Gels, with Particular
Reference to the Study of Mutation • MichaelM. SkolnickandJames V. NeelThe Human Argininosuccinate Synthetase Locus and Citrullinemia • Arthur L Beaudet.
William E. O'Brian. Hans-Georg O. Bock,Svend O. Freytag. andTsung-Sheng SuMolecular Genetics of the Human Histocompatibility Complex. CharlesAuffrayand
Jack L StromingerGenetics of Human Alcohol and Aldehyde Dehydrogenases • MoyraSmith
VOLUME 16 (1987)Genetics of Lactose Digest ion in Humans • GebhardFlat;Perspectives in the Teaching of Human Genetics • RonaldG. Davidsonand BartonChildsInvestigation of Genet ic Linkage in Human Families • Ray Whiteand Jean-MarkLalouelChronic Granulomatous Disease • John T. CurnutteandBernardM. BabiorGenetics of Steroid Receptors and Their Disorders • LeonardPinkskyand Morris Kaufman
VOLUME 17 (1988)Chorionic Villus Sampling • James D. Goldbergand MitchellS. GlobusThe Molecular Genetics of Hemophilia A and B in Man: Factor VIII and Factor IX Deficiency
• Stylianos E. AntonarakisCloning of the DuchennelBecker Muscular Dystrophy Locus • AnthonyP. Monaco and
Louis M. KunkelTrisomy 21: Molecular and Cytogenetic Studies of Nondisjunct ion • GordonD. Stewart,
Terry J. Hassold, and David M. KurnitMolecular Gentics of Human Salivary Proteins and Their Polymorph isms • EdwinA. Azen
and Nobuyo Maeda
VOLUME 18 (1989)The Molecular Basis of HLA-Disease Association • J. I. Bell. J. A. Todd. and H. O. McDevittChromosome Instability Syndromes • MaimonM. Cohenand HowardP. LevyLacticademia: Biochemical, Clinical and Genetic Considerations • BrianH. RobinsonA Comprehensive and Critical Assessment of Overgrowth and Overgrowth Syndromes •
M. Michael Cohen. Jr.Genetics of Growth Hormone and Its Disorders • John A. PhillipsIII and
CindyL Ynencak-Iones
VOLUME 19 (1990)The Lethal Osteochondrodysplasias • JurgenSprangerand PierreMaroteauxMutations in Type I Procollagen Genes that Cause Osteogenesis Imperfecta •
Darwin J. Prockop, ClintonT. Baldwin, and Constantinos D. ConstantinouStructural Defects in Inherited and Giant Platelet Disorders • James G. WhiteGenetic Aspects of Immunoglobulin A Deficiency • Charlotte Cunningham-RundlesOxidative Phosphorylation Diseases : Disorders of Two Genomes • JohnM. ShoffnerIV and
Douglas C. Wallace
Contents of Earlier Volumes
VOLUME 20 (1991)Clinical and Molecular Genetics of Congenital Adrenal Hyperplasia Due to 2 I-Hydroxylase
Deficiency • YvesMorel and WalterL. MillerGenetic Aspects of Amyloidosis • DanielR. Jacobsonand Joel N. BuxbaumHuntington's Disease. James F. GusellaBiochemical and Molecular Genetics of Cystic Fibrosis • Lap-CheeTsui and
Manuel BuchwaldMolecular Genetics of von ReckJinghausen Neurofibromatosis • MargaretR. Wallace and
Francis S. Collins
VOLUME 21 (1993)Peroxisomal Diseases • Hugo W. MoserX-Linked Immunodeficiencies • JenniferM. PuckGenetic Mutations Affecting Human Lipoprote ins, The ir Receptors, and Their Enzymes •
Vassilis I. Zannis, Dimitris Kardassis, and Eleni Economou ZanniGenet ic Aspects of Cancer • Audrey D. Goddardand EllenSolomonGaucher Disease : Enzymology, Genetics, and Treatment • GregoryA. Grabowski
xi
Preface to Volume 1
During the last few years the science of human genetics has been expanding almost
explosively. Original papers dealing with different aspects of the subject are
appearing at an increasingly rapid rate in a very wide range of journals, and it
becomes more and more difficult for the geneticist and virtually impossible for thenongeneticist to keep track of the developments. Furthermore , new observationsand discoveries relevant to an overall understanding of the subject result frominvestigations using very diverse techniques and methodologies and originatingin a variety of different disciplines. Thus, investigations in such various fields asenzymology, immunology, protein chemistry, cytology, pediatrics, neurology,
internal medicine, anthropology, and mathematical and statistical genetics, toname but a few, have each contributed results and ideas of general significanceto the study of human genetics. Not surprisingly it is often difficult for workersin one branch of the subject to assess and assimilate findings made in another. Thiscan be a serious limiting factor on the rate of progress.
Thus , there appears to be a real need for critical review which summarizes thepositions reached in different areas, and it is hoped that Advances in HumanGenetics will help to meet this requirement.
Each of the contributors has been asked to write an account of the positionthat has been reached in the investigations of a specific topic in one of the branchesof human genetics. The reviews are intended to be critical and to deal with thetopic in depth from the writer's own point of view. It is hoped that the articles willprovide workers in other branches of the subject, and in related disciplines, with adetailed account of the results so far obtained in the particular area , and helpthem to assess the relevance of these discoveries to aspects of their own work, as
well as to the science as a whole . The reviews are also intended to give the readersome idea of the nature of the technical and methodological problems involved,and to indicate new directions stemming from recent advances.
The contributors have not been restricted in the arrangement or organi zation
xiii
xlv Prefaceto Volume 1
of their material or in the manner of its presentation, so that the reader should beable to appreciate something of the individuality of approach which goes to makeup the subject of human genetics, and which, indeed, gives it much of itsfascination.
HARRY HARRIS
The Galton LaboratoryUniversity College London
KURT HIRSCHHORN
Division of Medical GeneticsDepartment of Pediatrics
Mount Sinai School of Medicine
Preface to Volume 10
This is the tenth volume of Advances in Human Genetics and some fifty different
reviews covering a very wide range of topics have now appeared. Many of theearlier articles still stand as valuable sources of reference . But the subjectcontinues to move forward at an increasing speed and its vitality is indicated by itsremarkable recruitment of young investigators. New areas of research which could
hardly have been envisaged only a few years ago have emerged, and quiteunexpectedly discoveries have been made in part s of the subject which onlyrecently had come to be thought as fully explored. So there continues to be a needfor authoritative and critical reviews intended to keep workers in the various
branches of this seemingly ever-expanding subject fully informed about theprogress that is being made and also , of course , to provide a ready and access ibleaccount of new developments in human geneti cs for those whose primary interestsare in other fields of biological and medical research .
We see no reason to alter the general policy which was outlined in the prefaceto the first volume . We believe that it has served our readers well. The subjec tseems to us to be just as exciting and intellectually stimulating and rewarding asit did when this series was first started. We expect the next decade of research inhuman genetics to be as innovative and productive as the last and our aim is to
record its progress in Advances in Human Genetics .
H ARRY H ARRIS
University of Pennsylvania, Philadelphia
K URT HIRSCHHORN
Mount Sinai School of Medicine of the CityUniversity of New York
xv
Contents
Chapter J
Genetic Disorders of Pigmentation
Richard A . Spritz and Vincent J. Hearing , Jr.
Introduction IThe Mammalian Pigmentary System 2
Disorders of Melanocyte Function 8Albinism 8Type I (Tyrosinase-Deficient) OCA (MIM #203100) 8
Type II (Tyrosinase-Positive) OCA (MIM #203200) 15Type IV (Brown) OCA (MIM #203290) . . . . . . . . . . . . . . . . . . . . . . . . 19X-linked Recessive Ocular Albinism , Nettleship-Falls Type (OA I ;
MIM #300500) 20Disorders of Melanocyte Development: Piebaldism and Waardenburg
Syndrome 21Piebaldi sm (MIM # 172800) 21Waardenburg Syndrome (MIM # 193500) 26
Other Cloned Gene s Affecting Pigmentation in the Mouse 29
Mottled . . . . . . . . . .. .. . . . . . . . .. . . .. . . . . . . . . . . . . . . . . . . . . . . . .. 30Pallid 30Pearl 31Microphthalmia 31Dilute 32Exten sion 32Agouti 32Slaty 33
xvii
xviii Contents
Silver 34References 34
Chapter 2
High-Resolution Replication Bands Compared with MorphologicG- and R-Bands
Regen Drouin, Gerald P. Holmquist, and Claude-Lise Richer
Introduct ion 47Arrest of DNA Replication by DNA Synthesis Inhibitors . . . . . . . . . . . . . 51BrdUrd Incorporation and S-Phase 53BrdUrd Detection 58
Fluorochrome-Photolysis-Giemsa Staining Technique . . . . . . . . . . . . . . 59BrdUrd Antibody-Binding (BAB) Technique . . . . . . . . . . . . . . . . . . . . . 68
Comparative Band Pattern Analysis 70Replication Band Patterns 70Replication Band Patterns versus Morphologic Band Patterns 73Juxtacentromeric Area . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85C-band Area 85Telomeric Area 86Inactive X-Chromosome 87Homolog Discordance 88Lateral Asymmetry 90
RIG Transition and 3C Pause 92Quantification of R-, G- and C-band Chromatin . . . . . . . . . . . . . . . . . . . . 93Condensation and Replication: Two Interrelated Phenomena 95Features of R- and G-bands 99Conclusion 100Acknowledgments 101References 10I
Chapter 3
Molecular Genetics of Charcot-Marie-Tooth Neuropathy
Benjamin B. Roa and James R. Lupski
Introduction 117
Contents xix
Pathological Features I 18Charcot-Marie-Tooth Disease 118Inherited Primary Peripheral Neuropathies Related to CMT I 19
Genetic Heterogeneity of Charcot-Marie-Tooth Disease . . . . . . . . . . . . . . 120Gene Dosage as a Novel Mechanism for CMT Type IA 121
DNA Duplication as the Major Cause of CMTl A 121The Region Duplicated in CMTlA is Flanked by Large Regions of
Homology 122Evidence Supporting the Gene Dosage Model for CMTlA 124
The PMP22 Gene in Charcot-Marie-Tooth Disease and InheritedPrimary Peripheral Neuropathy 128
PMP22 and Charcot-Marie-Tooth Disease Type IA 128PMP22 and the Dejerine-Sottas Syndrome 129PMP22 and Hereditary Neuropathy with Liability to Pressure Palsies 129
Genes Associated with Other Forms of CMT 132The Myelin Protein Zero (MPZ) Gene and CMTl B . . . . . . . . . . . . . . . 132MPZ and Dejerine-Sottas Syndrome 133The Cx32 Gene and X-linked CMT . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
Implications of CMT Studies on Peripheral Nerve Biology 133Genetic Diagnosis for CMT and Associated Neuropathies 135
Detection of the CMTl A Duplication 135Mutation Analysis of Genes Associated with CMT 138
Molecular Insights Related to the CMT IA Duplication 139CMTlA Duplication and HNPP Deletion at the 17pl1.2pl2 Region 139Homologous Recombination in Model Systems 140DNA Rearrangements Associated with Disease Phenotypes 141
Conclusions 143Acknowledgments 145References 145
Chapter 4
Marfan's Syndrome and Other Microfibrillar Diseases
Harry C. Dietz, Francesco Ramirez , and Lynn Y. Sakai
Introduction 153Elastic Fibers and Microfibrils 154
Organization and Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
xx Contents
Composition 157Fibrillins 161
Protein Structure 161Gene Structure 166Microfibrillar Assembly 166
Marfan's Syndrome 168Clinical Features 168Clinical Management 172Fibrillin Mutations 173Intrafamilial Variability 178
Marfan-Like Conditions 180Conclusions and Future Prospectives 181Acknowledgments 182References 182
Chapter 5
Nonisotopic in Situ HybridizationClinical Cytogenetics and Gene Mapping Applications
Matteo Adinolfi and John Crolla
Introduction 187The Probes 190Detection by NISH of Chromosomal Disorders in Metaphase Spreads . . 194
Translocations and Isochromosomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195Marker Chromosomes 198Deletions and Duplications 204
Detection by NISH of Chromosomal Abnormalities in Cells inInterphase 215
Prenatal Tests on Cells in Interphase by NISH 215Detection of Mosaicism 221Radiation Induced Chromosomal Damage . . . . . . . . . . . . . . . . . . . . . . . 222Somatic Pairing 223
NISH and the Mapping of the Human Genome 223Metaphase Mapping 224Interphase Mapping 227
Cancer and NISH Analysis of Chromosomal Defects . . . . . . . . . . . . . . . . 228Evolution 232