基因的结构和功能 Gene Structure and Function.ppt

Exons and introns can be changed Gene clusters Human hemoglobins Transcription factors (TFs) Response elements: regulated in response to certain TFs Each TF has a specific binding sequence TFs have primary responsibility for recognizing promoter, binding to the RNA pol and positioning it correctly at the startpoint cis-acting elements in promoter Formation of pre-initiation complex The regulatory region of human metallothionein gene Splicing Occurs in the nucleus, together with other modifications (5’Cap, 3’Poly A) Three major mechanisms to remove introns Spliceosome Catalytic RNA Enzymatic removal (yeast tRNA) Gene Structure and Expression Human Gene Intron Structure 15 nt 7 nt 6 nt Mutations may or may not result in an expressed phenotype. - Mutations can alter RNA expression, processing and/or stability. Mutations that have no phenotype are called neutral mutations. A mutation is a structural change in genomic DNA sequence due to errors in DNA replication or repair. - Mutations can also affect protein expression, processing, stability. Mutations can be inherited (genetic/germline mutations) not inherited (somatic mutations) Mutations 1. Point mutations: change in one base pair of DNA. (1) silent mutations: changes in DNA which do not affect protein expression or function. (2) missense mutations: changes in DNA which lead to a change in an amino acid. (3) nonsense mutations: changes in DNA which generate a termination codon and thus stop translation. (4) Regulatory mutations: one which involves the promoter or another regulatory sequence such as an enhancer, silencer, or locus control region. (5) RNA processing mutations: These affect the processing of the primary RNA transcript to form mRNA, either by altering normal RNA splicing or by preventing either normal 5’-capping or 3’-polyadenylation. Structural classification of mutations Silent mutation Missense mutation Non-sense mutation Frameshift mutation Types of Mutation