(临床遗传课件)Chapter4 Genetic Variation in Individuals Mutation and Polymorphism讲解材料.pptVIP

Genetic Variation in Individuals and populations: Mutation and Polymorphism;Outline;MUTATION (突变); 1. Genome Mutations（基因组突变）: mutations that affect the number of chromosomes in the cell 2. Chromosome Mutations（染色体突变）: mutations that alter the structure of individual chromosomes 3. Gene Mutations（基因突变）: mutations that alter individual genes;47, XY, +21; DNA replication errors;Examples of Gene Mutations;Categories of Mutation and Their Estimated Frequencies Class of Mutation Mechanism Frequency Examples Genome mutation chromosome 10-2/cell division Aneuploidy missegregation Chromosome chromosome 6?10-4/cell division Translocation mutation rearrangment Gene mutation base-pair mutation 10-10/base pair/cell division Point mutation 10-5-10-6/locus/generation;Types of mutations;MUTATION;;MUTATION;A hereozygous C to T mutation converts arginine codon (CGA) to terminate codon (TGA) ;MUTATION;RNA splicing;MUTATION;MUTATION;Wild type;Dynamic mutations (动态突变): Mutations in some disorders involve amplification of trinucleotide repeat sequences during gametogenesis. Become mutated through a two-step process. The first mutation, called the premutation, doesnt cause any clinical symptoms. A second mutation was required to convert the premutation into a full mutation capable of causing the clinical symptoms ;Nature Reviews Genetics 2010 Vol 11 786-99;? The position of a mutation is designated as being in genomic (i.e., nuclear) DNA, cDNA sequence, mitochondrial DNA, or protein by the prefix g., c., m., or p., respectively. In cDNA, the A of the translational start ATG is designated +1. The next base upstream is -1; there is no 0. The amino-terminal methionine is numbered +1 in the protein. ?;1. A nuc