What is a missense mutation.
- Substitution or deletion of base pairs in DNA leading to misreading of the DNA code and replacement of an aa with other.
- If it does not alter fxn: conservative misense mutation or if alters fxn then nonconservative missensse mut
- It can also change an aa codon to a stop codon (UAG) - results in a truncated protein --- nonsense mutation
What are the consequences of mutations within introns (non-coding sequences)?
Introns contain promoter and enhancer regions, deletions interfere with binding of transcription factors --- leading to reduced or absent transcription
What is a frameshift mutation?
- If deletions or insertions are not in multiples of 3, it can shift the entire reading frame for transcription and have a major effect on the end protein - ex. Tay-Sachs dz - 4 base pair insertion - see figure
- But if the deletion or insertion is in a multiple of 3 then one aa may be missing but you do not get the frame shift.
List and describe the transmission patterns of single gene disorders.
- 1) Autosomal dominant - see in heterozygous state, can variable penetrance (only % with mutation will express trait) and expressivity (expressed differently in each indiv), enzymes usually NOT affected, delayed age of onset
- 2) Autosomal recessive - early onset, uniform defect, full penetrance usually
- 3) X-linked - het females express dz partially
List the 4 mechanisms involed in single-gene disorders.
- 1) Enzyme defect
- 2) Receptor and transport system defect - ex. LDL receptor defect ---- hyperchol d/t no LDL uptake
- 3) Alteration of nonenzyme proteins - sickle cell anemia, thalassemia, collagen, spectrin (hered. sphero)
- 4) Genetic adverse drug rxn - G6PD def
Describe the pathogenesis of familial hypercholesterolemia.