Human Genetics: The Molecular Revolution
This text is a survey of the current status of human genetics with an emphasis on the impact of molecular information. It focuses not only on fundamental knowledge about genome organization, function, and variation, but also on understanding, diagnosis, and treatment of genetic disease.Introduction -- Some historical highlights -- Molecular era -- Organization the human genome -- General features of human chromosomes -- Families of reiterated sequences account for about one-third of the human genome -- Many structural genes occur in small families of closely related sequences -- Most protein-coding genes have a complex internal organization -- Psuedogenes are common -- Structure and variation of specific genes -- Total number of human genes is unknown -- Gene mapping I: physical maps -- Gene mapping by somatic cell hybridization -- Gene mapping by in situ hybridization -- Isolation of individual chromosomes -- Top-down approach to molecular mapping -- Restriction maps and contig -- Construction: the bottom-up approach -- DNA sequencing -- Gene mapping, II: linkage analysis and genetic maps -- Restriction fragment length polymorphisms and linkage analysis in humans -- Linkage analysis with autosomal dominant diseases -- Linkage analysis with autosomal recessive diseases -- Linkage analysis can provide evidence of genetic heterogeneity -- Linkage equilibrium and disequilibrium(cont) Identifying the genetic basis of disease -- Typical positional analysis experimental strategy -- Positional analysis and specific diseases -- Mutation: quantitative aspects -- Mutation rates in germ cells -- Impact of mutation on disease -- Somatic mutation in humans -- Mutation: qualitative aspects -- Mutations involving one or a few nucleotides -- Deletions and insertions -- Chromosomal mutations -- Dominance and recessiveness, penetrance and imprinting: some molecular explanations -- Molecular explanations of dominance and recessiveness -- Molecular explanations of incomplete penetrance and variable expressivity -- Genomic imprinting -- Genetic screening and prenatal diagnosis -- Genetic screening -- Prenatal diagnosis -- Treatment of genetic disease -- Gene therapy -- Traditional treatment modalities -- Genetic basis of cancer -- Oncogenes: growth promoters -- Tumor suppressor genes -- Functions of proto-oncogenes and oncogenes -- Role of oncogenes in tumor formation -- Genetics of the immune system -- B cells and the antibody response -- T cell response: cell-mediated immunity(cont) Major histocompatibility complex -- Tolerance and autoimmunity -- Deficiency disorders of the immune system -- X and Y chromosomes -- Molecular biology of the X chromosome -- Molecular biology of the Y chromosome -- Patterns of inheritance -- Examples of X-linked diseases -- Mitochondrial genome and its pathology -- Mitochondrial structure and function -- Mitochondrial genetic diseases -- Human genome project -- Initial concerns -- Organization of the human genome project -- International scene
