Human Hemoglobin Genetics

1. Introduction.- A. The Hemoglobins in Human Biology and Genetics - An Overview.- B. Historical Foundations of Human Hemoglobin Genetics.- 2. The Human Hemoglobins.- A. Hemoglobin Structure and Function.- B. The Normal Human Hemoglobins and Their Globin Subunits.- 3. The Human Globin Genes.- A. DNA Structure and Function.- B. Recent Methodologie Advances in the Study of Genes and Their Structure.- C. Globin Gene Localization and Organization.- D. The Structure of the Globin Genes.- E. The Evolution of the Globin Genes.- 4. Hemoglobin Synthesis and Globin Gene Expression.- A. Hemoglobin Synthesis and Its Regulation.- B. Regulation of the Expression of the Normal Globin Genes.- 5. The Globin Gene Mutations - A. Mechanisms and Classification.- A. Mechanisms of Globin Gene Mutation.- B. Classification of the Globin Gene Mutations.- 6. The Globin Gene Mutations - B. Their Phenotypes and Clinical Expression.- A. Sickle Cell Disease.- B. Intracellular Hemoglobin Crystallization: Hb C.- C. Erythrocytosis: Abnormal Hemoglobins with Increased Oxygen Affinity.- D. Congenital Cyanosis.- E. Hemolytic Anemia ("Congenital Heinz-Body Anemia"): The Unstable Hemoglobins.- F. The Thalassemias.- G. The Syndromes of Hereditary Persistence of Fetal Hemoglobin.- H. Precocious Synthesis of Adult Hemoglobin.- 7. The Genetics of the Human Globin Gene Loci: Formal Genetics and Gene Linkage.- A. The Formal Genetics of the Human Hemoglobin System.- B. New Globin-Gene Mutations.- C. Aequired (Non-genetic) Thalassemias.- D. Linkage Relationships Involving Polymorphic Sites in the Regions of the Globin Genes.- 8. The Geographic Distribution of Globin Gene Variation.- A. Distribution of the Hemoglobin Variants and Thalassemias.- B. The Malaria Hypothesis.- C. Molecular Approaches to theStudy of Genetic Diversity of the Globin Gene Alleles.- 9. Laboratory Identification, Screening, Education, and Counseling for Abnormal Hemoglobins and Thalassemias.- A. The Laboratory Identifieation of Abnormal Hemoglobins and Thalassemias.- B. Screening for Abnormal Hemoglobins and Thalassemias.- C. Antenatal Diagnosis.- 10. Approaches to the Treatment of the Hemoglobin Disorders.- A. Current Forms of Treatment for Patients with Hemoglobin Disorders.- B. New Directions in Therapy.- Table A-1. The ?-Globin Gene Mutations.- Table A-2. The ?-Globin Gene Mutations.- Table A-3. The ?-Globin Gene Mutations.- Table A-6. The Fusion Gene Mutations.- References.