.................................................................................................................................. iii DECLARATION ............................................................................................................................ v ACKNOWLEDGEMENTS ........................................................................................................... vi TABLE OF CONTENTS .............................................................................................................. vii LIST OF FIGURES ..................................................................................................................... viii LIST OF TABLES ......................................................................................................................... ix LIST OF ABBREVIATIONS ......................................................................................................... x CHAPTER ONE: LITERATURE REVIEW AND THESIS RATIONALE .................................. 1 CHAPTER TWO: METHODS ..................................................................................................... 27 CHAPTER THREE: RESULTS AND ANALYSIS..................................................................... 36 CHAPTER FOUR: DISCUSSION AND CONCLUSION........................................................... 56 REFERENCES ............................................................................................................................. 65 APPENDICES .............................................................................................................................. 77 APPENDIX I: Outline of PHRED and PHRAP ........................................................... 77 APPENDIX II: List of Perl scripts................................................................................. 79