A Primer of Human Genetics

Greg Gibson is Professor and Director of the Center for Integrative Genomics at the Georgia Institute of Technology, and holds an adjunct appointment at Emory University School of Medicine. He earned a Bachelor's Degree in Biology at the University of Sydney and a Ph.D. in Cell Biology at the University of Basel (with Walter J. Gehring). He worked for 15 years with the fruitfly Drosophila melanogaster, mostly while at North Carolina State University, during which time he wrote A Primer of Genome Science with Spencer Muse. Dr. Gibson serves on the editorial boards of several leading journals, and is a Fellow of the American Association for the Advancement of Science. His current research is in quantitative genetics and genomics, focusing on environmental and genetic sources of human variability, the regulation of gene expression in immunogenomics, and predictive health.

PART I. FOUNDATIONS 1. Conceptual Foundations.- BOX. Some Fundamental Principles of Quantitative Genetics.- Heritability.- Mendelian Genetics.- Rare Alleles of Major Effect.- Common Disease-Common Variant.- The Infinitesimal Model.- Conclusions and Synthesis.- 2. The Human Genome.- Chromosome Content.- Gene Content.- Gene Structure.- Gene Regulation.- RNA Genes.- Repetitive Elements.- Sequence Variation.- 3. Human Evolution.- Homo sapiens.- Human Dispersal: Out of Africa.- Human Population Structure.- Recombination and Linkage Disequilibrium.- Demographic Processes.- Purifying Selection.- Adaptation.- Why Do We Get Sick?.- 4. Normal Variation.- Pigmentation.- Height.- Weight.- Intelligence and Temperament.- Specific Behaviors.- Miscellaneous Traits.- 5. Personalized Genomics.- Concerns over Personal Genome Projects.- BOX. Consent and Responsible Conduct of Research.- Existing PGP Studies.- Prenatal Diagnostics.- Postnatal Diagnosis.- Genome Sequence-Enabled Unbiased Mutation Identification.- Genetic Counseling.- Pharmacogenetics.- Integrated Health.- PART II. TOOLS 6. Genome-Wide Association Studies.- First GWAS.- Basic Methodology.- BOX. Summary of an Association Study.- Population Structure.- Fine Mapping.- Causal Inference.- Interaction Effects.- Polygenic Risk and SNP-Based Heritability.- Genotyping Technologies.- 7. Whole-Genome and Whole-Exome Sequencing.- Sequencing Technology and Strategy.- Whole-Exome Sequencing.- BOX. Pedigree Mapping.- Copy Number and De Novo Variation.- Whole-Genome Sequencing.- Inference of Deleteriousness.- Candidate Gene Mapping.- Emerging Technologies.- 8. Gene Expression Profiling.- Microarray Analysis.- RNA Sequencing.- Basic Statistical Issues in Transcriptome Analysis.- Gene Ontology and Downstream Analysis.- Atlases of Gene Expression.- Biomarkers and Disease Progression.- Genome-Environment Interactions.- Genetics of Gene Expression Variation.- 9. The Epigenome.- The ENCODE Project.- Chromatin Profiling with DNase Hypersensitive Sites.- Chromatin Conformation Capture.- Methylation Profiling.- BOX. Methylation Analysis in Biology.- The Histone Code.- Chromatin Immunoprecipitation.- 10. Integrative Genomics.- Proteomics.- Metabolomics.- Metagenomics.- Integrative Genomics: Case Studies.- PART III. DISEASES 11. Immune-Related Disease.- Review of the Immune System.- Variable Responses to Pathogens.- Inflammatory Bowel Disease.- Type 1 Diabetes.- Other Autoimmune Diseases.- Primary Immune Deficiency.- 12. Metabolic Disease.- Primary Dyslipidemia and Hypercholesterolemia.- Quantitative Regulation of Lipid Traits.- Genetics of Blood Glucose and Insulin Levels.- Genetics of Type 2 Diabetes.- Evolution of Diabetes Risk.- The T2D Microbiome.- Nutrigenetics.- 13. Cardiovascular Disease.- Hypertension.- Platelet and Erythrocyte Function.- Arteriosclerosis.- Myocardial Infarction.- Mendelian Randomization.- Arrhythmia.- Cardiomyopathy.- Congenital Heart Defects.- 14. Cancer Genetics.- BOX. Familial Cancer Syndromes.- Conceptual Foundation.- Breast Cancer.- Prostate Cancer.- Lung Cancer.- Colorectal Cancer.- Leukemia.- Melanoma.- Glioblastoma.- Pan-Cancer Analysis.- 15. Neurological and Psychiatric Disorders.- Autism.- Schizophrenia.- Intellectual Disability.- Major and Bipolar Depression.- Epilepsy.- Evolving Mental Health.- [7 figures].- 16. Genetics of Aging.- Alzheimer's Disease.- Parkinson's Disease.- Age-Related Organ Failure.- Degenerative Bone Disease.- Biochemical Pathways of Aging.- Genomics of Human Longevity.- Concluding Remarks.- Glossary.- Index.