Advances in Human Genetics 11 [Paperback]

1 The Pi Polymorphism: Genetic, Biochemical, and Clinical Aspects of Human ?1-Antitrypsin.- Historical Review.- Pi Variants.- Nomenclature of Genetic Variants.- Techniques for Identification.- Characterization of Pi Variants.- Population Studies of the Pi Alleles.- Linkage and Mapping for the Pi Locus.- Selective Mechanisms.- Biochemical Aspects.- Microheterogeneity.- Antigenicity.- Inhibition of Proteases.- ?1-Antitrypsin and the Clotting System.- ?1-Antitrypsin and the Immune Response.- Biochemical Characterization of Genetic Variants of ?1-Antitrypsin.- Metabolism of ?1-Antitrypsin.- Synthesis and Distribution.- Concentration of ?1-Antitrypsin in Plasma.- Association between Pi Types and Disease.- Pulmonary Disease.- Liver Disease.- Primary Liver Carcinoma.- Other Malignancies.- Kidney Disease.- Rheumatoid Arthritis.- Miscellaneous Diseases.- Chromosome Aberrations.- Protease Inhibitor Systems and Disease Mechanisms.- Interrelated Systems.- Leukocyte Proteases and ?1AT.- Unresolved Problems.- References.- 2 Segregation Analysis.- Mathematical Formulation of Genetic Models.- Joint Genotypic Distribution of Mating Individuals.- Relationship between Phenotype and Genotype.- Mode of Inheritance.- Sampling Scheme.- The Likelihood Method.- Likelihood of Randomly Sampled Data.- Likelihood When Sampling via Selected Probands.- Parameter Estimation and Testing Hypotheses.- Examples of Segregation Analysis.- Segregation of Dopamine-?-hydroxylase (DBH) Activity in Selected Families.- Segregation of Hypercholesterolemia in a Large Pedigree.- Segregation of Phenylthiocarbamide (PTC) Taste Sensitivity.- Segregation of Immunoglobulin E (IgE) Levels.- Conclusion.- Appendix: Notes on Computational Methods.- References.- 3 Genetic, Metabolic, and Biochemical Aspects of the Porphyrias.- Tetrapyrroles.- Structure of Porphyrins.- Physicochemical Properties of Porphyrins.- Enzymes and Intermediates of the Heme Biosynthetic Pathway.- Formation of ?-Aminolevulinic Acid (ALA).- FormationlS¶