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Molecular Biology and Applied Genetics MOLECULAR BIOLOGY AND APPLIED GENETICS FOR Medical Laboratory Technology Students Upgraded Lecture Note Series Mohammed Awole Adem Jimma University 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 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 i 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. ii 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. iii 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 iv 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 v 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 vi 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 vii 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 ...................................................... 232 10.3. Transformation................................................... 238 10.4. Transposition ..................................................... 241 10.5. Recombination................................................... 242 10.6. Plasmid .............................................................. 243 CHAPTER ELEVEN: TRANSCRIPTION AND TRANSLATION 11.0. Introduction ......................................................
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