1 Gene – Expression – Mutation - polymorphism

2 How are genes expressed ? Nucleus Cytoplasm DNA Transcription Poly(A ) Cap Pre-mRNA Splicing Cap Poly(A) mRNA Lariat intron Degradation mRNA transport Ribosome Translation PROTEIN

3 MUTATION Mutation is a change in the nucleotide sequence of genome, caused by a replication error or by a mutagen. Mutagen  a chemical or physical agent that can cause a mutation in a DNA molecule

4 The cause of mutations 1.Spontaneous error in replication that evade proofreading function of the DNA polymerases that synthesize new polynucleotides  mismatches

5 1. Error in replication

6 2. Effect of mutagen

7 Mutation : 1.Point mutation 2.Deletion 3.Insertion 4.Duplication In-frame mutation  maintain reading frame (codon is intact) Out of frame/frameshift mutation  disrupt reading frame

8 Point mutation  common (single site mutation) : replace one nucleotide with another Divided into two catagories: 1.Transitions : are purine-to purine or pyrimidine-to- pyrimidine changes : A  G, G  A, C  T, or T  C. 2.Transversions : are purine-to-pyrimidine or pyrimidine-to-purine changes: A  C, A  T, G  C, G  T, C  A, C  G, T  A or T  G

9 Point mutation: Single nucleotide change  - deletion - insertion - missense - nonsense (create a stop codon) - silent (no amino acid alteration)

10 Point mutation : Silent Missense

11 Polymorphism:  Different nucleotide sequence that occurs in the population as a whole Deletion Insertion Duplication Missense Silent Patient (+) Control (-) Patient (+) Control (+) Mutation Polymorphism Most polymorphism occurs in intronic sequence