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Basics ofHUMAN GENETICS
Second Edition
Basics ofHUMAN GENETICS
Second Edition
Versha Katira MBBS, MS (Anatomy), FIAMS (Genetics)
FormerProfessor and Head, Harsaran Dass Dental College, Ghaziabad
Vice-Principal, Professor and Head, Department of AnatomySantosh Medical College, Ghaziabad
Professor, Department of AnatomyChristian Medical College, Ludhiana, Punjab
Associate Professor and Head, Department of AnatomyLLRM Medical College, Meerut, Uttar Pradesh
CBS Publishers & Distributors Pvt Ltd
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Science and technology are constantly changingfields. New research and experience broaden thescope of information and knowledge. The author hastried her best in giving information available to herwhile preparing the material for this book. Althoughall efforts have been made to ensure optimumaccuracy of the material, yet it is quite possible someerrors might have been left uncorrected. Thepublisher, the printer and the author will not be heldresponsible for any inadvertent errors or inaccuracies.
ISBN: 978-93-86310-68-2
Copyright © Author and Publisher
Second Edition: 2017
First Edition: 2014
All rights reserved. No part of this book may be reproduced or transmitted in anyform or by any means, electronic or mechanical, including photocopying, recording,or any information storage and retrieval system without permission, in writing, from
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Preface to the Second Edition
I would like to thank my colleagues and students, whoseconstant endeavor inspired me to write this secondcomprehensive edition. Based on appropriate suggestions, thisedition includes detailed explanation of the basics of geneticswith illustrations, flowchart, etc. A new chapter on commongenetic disorders is supplemented with profound illustrations.Descriptive and objective questions have been given at the endof each chapter to improvise learning.
As the science of genetics is metamorphosed into interestingfacts, and becomes an integral part of medical education, I havetried to explain the basic underlying facts in detail. The bookcorrelates the basics of genetics with clinical aspects of commongenetic disorders in a lucid and easy-to-understand manner.Various branches of cytogenetics, biochemical and moleculargenetics are explained extensively for better understanding. Theclinical aspects have been outlined in tabular form, wherevernecessary. Hopefully, this assertive effort will surely helpundergraduate and postgraduate medical, dental andparamedical students in imbibing the elements of humangenetics.
Versha Katira
Preface to the First Edition
I have been encouraged by aspiring students and colleagues tomake an attempt diligently to unfold this interesting andfascinating branch of medical sciences. Recently, genetics hasbecome an essential and integral part of medical education,both at undergraduate as well as postgraduate levels. It is stillundergoing metamorphosis and gaining momentum rapidlyfor its expansion.
Thus, a suitable, comprehensive and compact textbook ofhuman genetics is unavoidable. Most of the students find thesubject too difficult to grasp and are not able to correlate theunderlying principles for most of the genetic disorders. Thus, Ihave tried to correlate the basics of genetics with clinical aspectsof some common genetic disorders in a simplified andunderstandable language and thus making the subjectinteresting.
Various branches of the subject, e.g. cytogenetics,biochemical genetics, molecular genetics, etc. have been dealtextensively for better understanding while the clinical aspectshave been briefly outlined in tabulated forms, whereverrequired.
I sincerely hope and wish that the first attempt will serve auseful and meaningful purpose in the field of medicine.
Versha Katira
Acknowledgements
I am extremely grateful to all the colleagues throughout mycareer in different colleges for giving the full support andcriticism on the first edition. Special thanks to Dr Molly Paul,Christian Medical College, Ludhiana, where I completed thefirst edition of this book. I owe my special thanks toDr (Mrs) Krishna Garg for her inspiration in writing the secondedition to this book.
I am extremely thankful to the editorial team at CBSPublishers & Distributors, New Delhi, and specially, Mr Y NArjuna, Sr Vice President, Publishing, Editorial and Publicity, for hisconstant encouragement.
I will gratefully acknowledge every comment andsuggestions from teachers and students leading toimprovements in the text as well as the illustrations.
Versha Katira
Contents
Preface to the Second Edition v
Preface to the First Edition vii
1. Historical Aspects 1–11• Introduction 1• Mendelian First Law of Segregation and Principle of
Unit Inheritance 3• Mendelian Second Law of Independent Assortment
and Principle of Dominance 4• History of Genetics 7• Selected Books on Historical Figures/Events in
Genetics 10
2. Introduction 12–15• Human Genetics 12• Branches of Genetics 13
3. Cytogenetics 16–42• Normal Chromosomes 16• Structure (Gross) 17• Classification (Gross)—General 19• Classification—Specific 20• Methods of Studying the Chromosomes 23• Behaviour of Chromosome During Cell Division 30• The Cell Cycle 31• Mitosis 34• Meiosis 36
– Significance of Meiosis 40
4. Molecular Genetics 43–62• DNA Organization of Chromosomes 43• Molecular Structure of Nucleic Acids (DNA and RNA) 45• DNA (Deoxyribonucleic Acid) 50• Chromosomal DNA 52
– Classification of DNA 52
xii Human GeneticsBasics of Human Geneticsxii
• RNA 53– Classification of RNA 53
• Gene and Genetic Code 54• Genetic Code 56
– Genetic Control on Protein Biosynthesis 58– Detailed Gene Structure 60
5. Mutation 63–66• Saltations, Sports, Discontinuous Variations or Point Mutations 63• Gene Mutation 63• Chromosomal Mutation 64• Genomatic Mutation (Heteroploidy) 65
6. Abnormal Chromosome 67–82• Numerical Abnormality 67
– Non-dysjunction 67• Structural Abnormality 69
– Robertsonian Translocation 75• Philadelphia Chromosome 77• Sister Chromatid Exchange (SCE) 78
7. Modes of Inheritance 83–101• Inheritance of Normal Morphological Traits 83
– Physiological Variations 84– Factors Leading to Variation in Expression of Genes 85
• Modes of Inheritance of Abnormal Traits 85– A Single Gene Defect 86– Chromosomal Defects 94– Multifactorial Defects 94
◊ Genetic Heterogeneity 95◊ Sex Limited and Sex Influenced Genes 95◊ Multiple Alleles 96◊ Polygenic Inheritance 97
• Gene Localization of Individual Chromosomes 98
8. Biochemical Genetics 102–135• Introduction 102• Inborn Errors of Metabolism 103• Blood Groups 113
Contents xiii
– ABO System 113– Bombay Phenotypes 116– Rh Blood Group System 116– Rh Null Blood Group and D/D Genotype 117– Prophylaxis against Rh Immunisation 118– MNS Blood Group System 118– Blood Group Chimeras 119– Role of Blood Groups in Human Genetics 119– Marker Genes and Disease Risks 122– Classification of Genetic Markers 123
◊ DNA Markers 123◊ Blood Group Markers 123◊ Genetic Markers in Serum 124◊ Human Lymphocyte Antigen System (HLA system) 124◊ Immunoglobulins as Markers 124◊ Chromosomes as Markers 124◊ Hepatoglobulins as Markers 124
• Haemoglobinopathies 125– Types of Haemoglobin Seen Normally in Human Beings 125
• Immunogenetics 128• Pharmacogenetics 133
9. Clinical Genetics 136–164• Population Genetics 136
– Hardy-Weinberg Principle 137• Multiple Births and Their Uses in Genetics 139• Dermatoglyphics 140
– Terminology Used in Dermatoglyphic 140– Methods Used for Obtaining the Dermatoglyphic Patterns 142– Uses and Limitations of Dermatoglyphic Analysis 143– Abnormal Dermatoglyphics 144
• Assessment and Evaluation of Genetic Disorders forGenetic Counselling 144– Karyotyping 151– Evaluation 151
• Genetic Counselling 156• Experimental Genetics and Eugenetics 157• Gene Therapy 159• Genetics of Cancer in Human 162
xiv Human GeneticsBasics of Human Geneticsxiv
10. Common Genetic Disorders 165–190• Down Syndrome 165
– Translocation Down Syndrome 167– Trisomy Involving Other Chromosomes 169– Adrenogenital Syndrome (Congenital Adrenal
Hyperplasia) 170– Cri-Du-Chat Syndrome 172– Turner’s Syndrome 173– Klinefelter or XXY Syndrome 175– Fragile X Syndrome 176– Congenital Hypothyroidism (Cretinism) 177– Craniosynostosis 178– Achondroplasia 180– Cleft Lip and Palate 181– Hydrocephalus 183– Phenylketonuria 184– Cornelia de Lange Syndrome 185– Congenital Pigmented Nevi 185– Sacrococcygeal Teratoma 187– Anorectal Malformations 187– Cystic Hygroma (Lymphangioma) 189
Glossary 191–202
Index 203–209
