Section IIB Flashcards
What are the three kind of base substitutions and what are their consequences?
- Silent substitutions: no consequence
- Missense mutations: change in **amino acid **
- nonsense mutations: Stop codon
What are the donor and acceptor sequences in splice sites? How can a mutation here cause an issue?
- GT…AG rule
- A mutation in the exon can move the splice site to within the intron or to take out part of the exon.
- sometimes a second GT donor site is created withen the exon resuling in abnormally and normally spliced mRNA products.
- Can activate cryptic sites
What is the major consequence of a 3bp insertion or deletion mutation?
-Adds or deletes one amino acid but does nt affect the reading frame
What is the major consequence of an inserition or deletion that is not a multiple of 3?
-it causes a frameshift that changes all downstream amino acids and will generally terminate the polypeptide early.
What are the properties of a gain-of-function muataion?
- typically domnant disorders
- result in overexpression of the product
Are loss-of-function mutations more often recessive or dominant?
- recessive unless 50% of protein product is not enough to maintain normal function, then it is dominant
- termed hypoinsufficiency
How many alpha and beta chains of Hb gene does a normal human have?
two beta
four alpha
which chain is defficient in alpha-thalassemia? what happens to the chain that is in excess?
- alpha chain is defficient, so the beta chain is in excess
- the Beta chains form homotetramers which have reduced O2 capacity leading to hypoxia
What happens to the excess alpha chains in Beta-thalassemia?
-alpha-chains form homotetramers that precipitate and damage the erythrocyte and lead to premature RBC destrction and anemia
What tyoe of mutation is induced by UV light?
base pair substitution
-pyrimidine dimers
What is the best known mutation hot spot?
- dinucleotide GC regions which are mostly 5-mythylcytosine
- cytosine is easily demethylated to thymine and a mutation occurs.
What DNA repair mechanism is responsible for repairing pyrimidine dimers?
-Nucleotide excision repair system
What does a defect in NER lead to?
Xeroderma pigmntosum
What is the cause of Cockayne Syndrome?
-defeective repair of UV-induced damage in transcriptionally acitve DNA
–very similar to XP
What is the cause and symptoms of Fanconi anemia?
-Cause unknown
–Anemia, leukemia susceptibility
