Genetic Variation Flashcards
What are the 5 types of single-gene mutations?
- Base-pair substitutions
- Insertions and deletions
- Duplications
- Control and structural types
- Unusual types
Describe base-pair substitution mutations. What are the three basic types?
This type of mutation is a change in one base pair.
- Silent mutation - occurs in the third (wobble) position resulting in no change in amino acids
- Missense mutation - changes in codon from one amino acid to another
- Nonsense - changes in codon results in a stop codon and premaure truncation of the protein
Describe insertion or deletion as a single-gene mutation.
How can the effect of this change based on the size of the sequence?
What is a frameshift mutation? What is likely a result of this?
This results in bases added to or removed from the sequence.
Large - can disrupt more than one gene
Small - can change the sequence.
When a number of bases is added or deleted, that is not a multiple of three, this results in a frameshift mutation. This changes the “reading frame” which results in a completely different amino acid sequence. Premature truncation is likely.
When non-coding DNA has mutations what could be effected that would change mRNA expression?
What could be effected that would change mRNA processing and protein sequence?
mRNA expression could be effected by changes to promoters, enhancers, and silencers.
mRNA processing and sequence could be effected by changes to splice sites.
What do most splice sites start and end with?
What could result from splice site mutations?
Introns typically start with GT and end with AG
Cryptic sites could become functional
Exon skipping could occur
Describe duplication mutations.
Large regions of DNA, sometimes whole genes duplicated.
Can effect gene function and gene dosage
Describe transposon mutation.
Transposons are mobile genetic elements that can insert in or near a gene which alters expression
Describe expanded repeats as mutations
Expanded repeats consist of trinucleotides, a run of one amino acid.
When this number increases to a certain threshold this can disrupt function.
What are the different ways that mutations effect function of genes?
- Loss of function - protein has no activity
- Gain of function - protein has new or greater activity
What is a polymorphism?
Give an example.
A gene with mutliple forms with frequency >1% and no deleterious effects.
Blood groups are a good example. ABO system and Rh system
What are the different types of hemoglobin mutations and examples?
- Structural mutations - change in proteins
ex: Sickle cell anemia (glutamate 6->valine) - Control of expression
ex: thalassemias, or persistence of fetal hemoglobin
What mutation causes Thalassemias? Which cell does it attack? What are clinical presentations?
Thalassemias are a hemoglobin mutation effecting control of expression.
Defect of either alpha- or beta-globin. With excess of one type of globin tetramers form of the other subunit.
Precipitation causes damage to RBCs which then have shorter lifespans.
This causes anemia and often splenomegaly.
What are three types of mutagens that can cause mutation?
What are the corresponding molecular mutations?
- Ionizing radiation - creating reactive radicals
this reacts with bases causing double-stranded breaks
- Nonionizing radiation - shift of electrons causing reactions
Ex: pyrimidine dimers formed by UV
- Chemicals - base analogs insert, react, change
Deamination reactions convert C to U
What are three factors that influence the rate of mutation of a gene?
- Size (larger size, larger target)
- Age at reproduction (longer time, more mutation)
- “hot spots” (CpG dimers)
Explain CpG dimer “hot spots”
An area of human DNA that is especially prone to mutation.
This is because CpG dimers are typically methylated. If a methylated C is deaminated this becomes a T. Then through mismatched repair the opposite strand is converted to an A to match.
This results in CG to TG mutation (per handout, this makes no sense to me)
