Human Genetics and Genomics

Bahar Taneri is a Professor of Molecular Biology and Genetics at Eastern Mediterranean University (EMU), Famagusta, Cyprus. After obtaining her Ph.D. degree in Biomedical Sciences, from The Rockefeller University, New York, USA in 2005, she has taught several Genetics and Genomics modules at EMU, where she has founded the Molecular Biology and Genetics undergraduate program. At EMU, she has served as the editor-in-chief of the University Research Newsletter for two years. She has also been chairing the Department of Biological Sciences since 2013. She is an affiliated Researcher of Institute for Public Health Genomics, Department of Genetics and Cell Biology, Faculty of Health, Medicine & Life Sciences at Maastricht University, Netherlands since 2011. She authored several publications in the field of genome biology and personalized medicine; and received several awards including a Fulbright Scholarship. Currently, her main research interests include human genomics, epigenomics and efficient translation of personalized genome-based findings into healthcare and medicine for prediction and prevention of common complex diseases. She is a founding member of the Medical Biotechnology Master's program at EMU, where she teaches modules including Genome Editing. Esra Asilmaz is currently a Locum Consultant in Gastroenterology and General Internal Medicine at Homerton University Hospital in London, UK. She obtained her Ph.D. degree in Molecular Genetics from The Rockefeller University, NYC, USA in 2004. She subsequently obtained her Bachelor of Medicine, Bachelor of Surgery degree in 2009 from St. George's University of London, UK. Between 2009-2011, she completed an Academic Foundation Programme at St. Thomas' and Guy's Hospital, London, UK. During this time, she worked at Professor Trembath's Laboratory of Human Genetics and was involved in the identification of Notch2 mutations in Hadju-Cheney Syndrome, a rare genetic condition. She was an Academic Clinical Fellow at University College Hospital, London, UK between 2011-2014 and was a member of Dr. Oben's laboratory at The Institute of Liver and Digestive Health. She obtained her MRCP (UK) Diploma in 2014 and Specialist Examination in Gastroenterology in 2016. She obtained her CCT in Gastroenterology and General Internal Medicine in September 2019. Turem Delikurt is a registered genetic counsellor. She graduated with a BSc in Biology from the University of South Dakota, USA in 2003. She completed her MSc in Genetic Counselling with a merit from the University of Manchester, UK in 2006. She has been working as a genetic counsellor in Cyprus since 2006. In 2015, she was registered by the European Board of Medical Genetics. Her main research interest is the exploration of genetic counselling in the context of culture. She is currently pursuing her Ph.D. degree, which is sponsored through the University of Plymouth, UK titled "Genetic Counselling in the Turkish Cypriot community". She is dedicated to increasing awareness about genetic conditions and genetic counselling, within her community. She penned a weekly column titled "Genetics Today" at one of the main newspapers in North Cyprus from 20004 until 2017. Over the years, she has been continuosly involved in various civil society activities aimed at increasing the quality of care and life of patients and families at risk of or affected by genetic conditions in Cyprus. Pembe Savas obtained her undergraduate degree in Medical Biochemistry from University of Leicester, UK in 2011 and further received an MSc degree in Reproductive Science and Women?s Health at University College London, UK in 2012. She has completed her project on pre-implantation genetic diagnosis of beta-thalassaemia at Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus, in 2012, where she gained hands-on laboratory experience. Since 2013, Pembe Savas is working as a senior instructor at the Department of Biological Sciences, Eastern Mediterranean University, Famagusta, Cyprus, where she is responsible for teaching numerous modules for the Molecular Biology and Genetics program; including Human Genetics. Her research interests include genetic testing in common complex diseases. Furthermore, since 2017 she has been actively involved in the Cyprus Women's Health Research Initiative. Seniye Targen obtained her undergraduate degree in Human Genetics from Newcastle University, UK, in 2009 and further specialized in the field of Human Molecular Genetics at Imperial College London, United Kingdom, in 2010, where she completed a project on X-linked cataract and Nance-Horan Syndrome. Upon completing her graduate degree, she has gained experience in private medical diagnostic laboratories. She had been employed as a laboratory instructor in the Department of Biological Sciences at the Eastern Mediterranean University, Famagusta, Cyprus, from 2013 to 2015. Currently, she is working towards a Ph.D. degree in molecular biology and genetics department with a particular focus on breast cancer biology at Bilkent University, Ankara, Turkey. Yagmur Esemen is currently working as a Foundation Year Two Doctor at Charing Cross Hospital, London, UK. In 2013, she completed her undergraduate degree in Neuroscience and Biology with honors at Lawrence University, WI, USA. As an undergraduate, she has been involved in various research projects in the fields of neuroscience, molecular biology and genetics. In 2011, she spent a summer at Mayo Clinics, Rochester, MN, USA studying the effects of Bro1 family members on Vps4 activity. Her senior thesis, completed in 2013, was on investigating the neural targets of DAF-19 in C. elegans, which was awarded Summa Cum Laude honours. She has received several awards including the Howard and Helen Russell Award for Excellence in Biological Sciences. Between 2013-2014, she worked as a laboratory instructor at the Department of Biological Sciences, Eastern Mediterranean University, Famagusta, Cyprus. She obtained her Bachelor of Medicine, Bachelor of Surgery degree with distinction from St. George's University of London, UK in 2018. Since then, she has been working as a foundation doctor in the North West Thames Foundation School in UK.

• About the Authors xiIntroduction xv1 Exploring Online Genetics Sources 1Background 1Human Genome Project 2National Center for Biotechnology Information (NCBI) 2UCSC Genome Browser 3The Encyclopedia of DNA Elements (ENCODE) 3Roadmap Epigenomic Project 5References 5Exercise Questions 6Additional Exercise Questions 112 Observation of Human Inheritance 13Background 13Mendelian Genetics 13The Transmission of Hereditary Characteristics 16Mendelian Disorders 19References 20Exercise Questions 21Additional Exercise Questions 223 Reading, Understanding, and Constructing Human Pedigrees 25Background 25Basic Pedigree Nomenclature 26Modes of Inheritance 26Autosomal Recessive Inheritance 28Pedigrees Representing Autosomal Recessive Inheritance 28Autosomal Dominant Inheritance 29Pedigrees Representing Autosomal Dominant Inheritance 30X-Linked Recessive Inheritance 30Pedigrees Representing X-Linked Recessive Inheritance 31X-Linked Dominant Inheritance 32Pedigrees Representing X-Linked Dominant Inheritance 32Y-Linked Inheritance 34Pedigrees Representing Y-Linked Inheritance 34Non-Mendelian Patterns of Inheritance 35Confounding Factors in Pedigree Generation and Interpretation 36References 36Exercise Questions 38Additional Exercise Questions 394 Cytogenetics 43Background 43Generation of Karyograms/Chromosome Banding 45FISH, Fluorescent In Situ Hybridization 47Comparative Genomic Hybridization (CGH) and Array-Based CGH Technology 48Chromosomal Abnormalities 48Numerical Chromosomal Abnormalities 49Structural Chromosomal Abnormalities 50References 51Exercise Questions 52Additional Exercise Questions 545 Exploring DNA, RNA, and Protein Sequence Databases and Genome Browsers 55Background 55General Biological Databases 57RNA-Specific Databases 59Protein-Specific Databases 61Regulatory DNA Database 62Genome Browsers 65References 67Exercise Questions 67Additional Exercise Questions 686 Exploring Online Bioinformatics Tools 71Background 71BLAST 71ExPASy 72Clustal Omega 74Reactome 76References 77Exercise Questions 77Additional Exercise Questions 797 Multifactorial Inheritance and Common Complex Diseases 81Background 81Polygenic Complex Diseases 82Investigating Complex Traits 82Obesity as a Complex Disease 83Diabetes Mellitus Type 2 as a Complex Disease 84Coronary Artery Diseases as Complex Diseases 85References 86Exercise Questions 88Additional Exercise Questions 888 Neurogenetics and Behavioral Genetics 91Background 91Genetic Regulation of Neural Development 91Structure and Function of the Nervous System 92Understanding the Genetics of Neurological Disease 94Examples of Neurogenetic Disorders 94Huntington’s Disease 94Parkinson’s Disease 95Rett Syndrome 95Behavioral Genetics 96Genetics of Depression 97Genetics of Drug Addiction 97Genetics of Schizophrenia 98References 99Exercise Questions 100Additional Exercise Questions 1019 Cancer Genetics 103Background 103Cell Cycle and Its Regulation 104Oncogenes and Tumor Suppressor Genes 105Carcinogens/Environmental Factors in Cancer 107Breast Cancer 108Role of Molecular Medicine in Breast Cancer Treatment 110Recent Advances in Cancer Diagnosis and Treatment 111References 112Exercise Questions 113Additional Exercise Questions 11410 Genetic Counseling 115Background 115References 117Exercise Questions 117Additional Exercise Questions 11911 Evolving Tools in Genome Editing: CRISPR-Cas 121Background 121Mechanism of CRISPR-Cas9 System 123Applications of CRISPR-Cas9 System 123Generation of Animal Models and Engineering Cells 123Somatic Genome Editing 124Repair of Genetic Disorders 124Functional Genomic Screening 124Treatment of Infectious Diseases 125Other Applications of CRISPR-Cas9 System 125References 126Acknowledgment 127Exercise Questions 127Additional Exercise Questions 128Glossary 129Index 139