FOR

Medical Laboratory Technology Students

Mohammed Awole Adem

Upgraded Lecture Note Series

Jimma University

MOLECULAR BIOLOGY AND APPLIED GENETICS

MOLECULAR BIOLOGY AND APPLIED GENETICS

For

Medical Laboratory Technician Students

Lecture Note Series

Mohammed Awole Adem

Upgraded - 2006

In collaboration with

The Carter Center (EPHTI) and The Federal Democratic Republic of Ethiopia Ministry of

Education and Ministry of Health

Jimma University

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PREFACE

The problem faced today in the learning and teaching of

Applied Genetics and Molecular Biology for laboratory

technologists in universities, colleges andhealth

institutions primarily from the unavailability of textbooks

that focus on the needs of Ethiopian students.

This lecture note has been prepared with the primary

aim of alleviating the problems encountered in the

teaching of Medical Applied Genetics and Molecular

Biology course and in minimizing discrepancies

prevailing among the different teaching and training

health institutions. It can also be used in teaching any

introductory course on medical Applied Genetics and

Molecular Biology and as a reference material.

This lecture note is specifically designed for medical

laboratory technologists, and includes only those areas

of molecular cell biology and Applied Genetics relevant

to degree-level understanding of modern laboratory

technology. Since genetics is prerequisite course to

molecular biology, the lecture note starts with Genetics

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followed by Molecular Biology. It provides students with

molecular background to enable them to understand

and critically analyze recent advances in laboratory

sciences.

Finally, it contains a glossary, which summarizes

important terminologies used in the text. Each chapter

begins by specific learning objectives and at the end of

each chapter review questions are also included.

We welcoming the reviewers and users input regarding

this edition so that future editions will be better.

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ACKNOWLEDGEMENTS

I would like to acknowledge The Carter Center for its

initiative, financial, material and logistic supports for the

preparation of this teaching material. We are indebted to

The Jimma University that support directly or indirectly

for the visibility of this lecture note preparation.

I extend our appreciation to the reviewers of the

manuscript during intra-workshop, Namely, Ato

Tsehayneh Kelemu , Biochemistry Department, School

of Medicine, and Ato Yared Alemu, School of Medical

Laboratory Technology, Jimma University.We greatly

appreciate them for their attitude, concern and

dedication.

I also acknowledge all reviewers of the manuscript

during inter-institutional workshop and those who

participated as national reviewers.

Last but not least I would like to acknowledge tyhose

who helped me directly or indirectly.

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TABLE OF CONTENTS

Preface ............................................................................ i

Acknowledgement.............................................................. iii

Table of Contents............................................................... iv

List of Figures ................................................................... xi

General objectives ............................................................. xiv CHAPTER ONE: THE CELL

1.0. Eukaryotic and Prokaryotic Cell .......................... 1 1.1. Function of the cell .............................................. 5 1.2. The chemical components of Cell membranes ... 8 1.3. Membrane structure............................................. 10

CHAPTER TWO: THE CELL CYCLE

2.0. Introduction .......................................................... 13 2.1. Control of the Cell Cycle ...................................... 15 2.2. Steps in the cycle................................................. 16 2.3. Meiosis and the Cell Cycle................................... 18 2.4. Quality Control of the Cell Cycle .......................... 18 2.5. Regulation of the Cell Cycle................................. 19

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2.6. Mitosis.................................................................. 23 2.7. Meiosis................................................................. 30 2.8. Comparison of Meiosis and Mitosis ..................... 33 2.9. Meiotic errors ....................................................... 33 2.10. Mitosis, Meiosis, and Ploidy............................... 34 2.11. Meiosis and Genetic Recombination.................. 35 2.12. Meiosis and Sexual Reproduction...................... 38

CHAPTER THREE: MACROMOLECULES

3.0. Introduction .......................................................... 40 3.1. Carbohydrate ....................................................... 41 3.2. Nucleic acids ....................................................... 43 3.3. Protein ................................................................. 46 3.4. Helix ..................................................................... 49 3.5. Tertiary structure.................................................. 58 3.6. Macromolecular Interactions................................ 63 3.7. Denaturation ........................................................ 64 3.8. Renaturation ........................................................ 69

CHAPTER FOUR: GENETICS

4.1. Mendelian genetics .............................................. 73 4.2. Mendel's first law: principle of segregation .......... 79 4.3. Mendel's second law: principle of independent assortment.. 80 4.4. Mendel's third law: principle of Dominance.......... 81

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4.5. Exception to Mendelian Genetics ........................ 82 CHAPTER FIVE: CHROMOSOME STRUCTURE AND FUNCTION

5.1. Chromosome Morphology.................................... 96 5.2. Normal Chromosome........................................... 97 5.3. Chromosome Abnormalities................................. 100 5.4. Types of Chromatin ............................................. 105 5.5. Codominant alleles .............................................. 106 5.6. Incomplete dominance......................................... 107 5.7. Multiple alleles ..................................................... 108 5.8. Epistasis............................................................... 108 5.9. Environment and Gene Expression .................... 109 5.10. Polygenic Inheritance ........................................ 110 5.11. Pleiotropy .......................................................... 112 5.12. Human Chromosome Abnormalities ................. 113 5.13. Cytogenetics ...................................................... 119

CHAPTER SIX: LINKAGE

6.0. Introduction .......................................................... 125 6.1. Mapping ............................................................... 128 6.2. Double Crossovers .............................................. 132 6.3. Interference.......................................................... 132 6.4. Deriving Linkage Distance and Gene Order from

Three-Point Crosses ........................................... 134

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CHAPTER SEVEN: PEDIGREE ANALYSIS

7.1. Symbols Used to Draw Pedigrees ....................... 145 7.2. Modes of inheritance............................................ 147 7.3. Autosomal dominant ............................................ 150 7.4. Autosomal recessive............................................ 151 7.5. Mitochondrial inheritance ..................................... 157 7.6. Uniparental disomy .............................................. 158

CHAPTER EIGHT: NUCLEIC ACID STRUCTURE AND FUNCTION

8.0. Introduction .......................................................... 161 8.1. Deoxyribonucleic acid .......................................... 162 8.2. Ribonucleic acid................................................... 167 8.3. Chemical differences between DNA & RNA ........ 170 8.4. DNA Replication................................................... 173 8.5. Control of Replication........................................... 191 8.6. DNA Ligation........................................................ 193

CHAPTER NINE:DNA DAMAGE AND REPAIR

9.0. Introduction .......................................................... 200 9.1. Agents that Damage DNA ................................... 201 9.2. Types of DNA damage......................................... 202 9.3. Repairing Damaged Bases .................................. 203 9.4. Repairing Strand Breaks...................................... 209

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9.5. Mutation ............................................................... 210 9.6. Insertions and Deletions ...................................... 214 9. 7. Duplications ........................................................ 216 9.8. Translocations...................................................... 219 9.9. Frequency of Mutations ...................................... 220 9.10.Measuring Mutation Rate.................................... 223

CHAPTER TEN: GENE TRANSFER IN BACTERIA

10.0. Introduction ........................................................ 226 10.1. Conjugation........................................................ 227 10.2. Transduction .....................................