Gene – Expression – Mutation - polymorphism

Telomere 1p32.2 Short arm (p) Centromere Long arm (q) Telomere

Human Chromosome: 22 pair autosomal 1 pair sex

Basic genetic principles 22 pasang autosomal kromosom 1 pasang sex kromosome Laki-laki XY, wanita XX Total: 46 kromosom

X-linked inheritance: XY XX Female carrier Male patient XX XY XX XY XY XX XX XY XX XY XY XX XY XY

Factors which can influence the phenotype

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

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

Consepts Mutation is the key processes responsible for genome evolution Mutation has various effects on genome function Some cells can modify their repair processes to induce hypermutation and bacteria may be able to carry out programmed mutations

Consepts …… Most mutations can be corrected by DNA repair processes which include excision procedures by removing damaged nucleotides and mismatch repair systems for correcting replication errors.

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

1. Error in replication

The cause of mutations 2. A mutagen that has reacted with the parent DNA, causing a structural change that affects the base-pairing capability of the altered nucleotide.

2. Effect of mutagen

Mutation : In-frame mutation  maintain reading frame (codon is intact) Out of frame/frameshift mutation  disrupt reading frame Point mutation Deletion Insertion Duplication

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

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

Point mutation : Missense Missense Silent

Deletion mutation: In-frame Out of frame

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