Genetic Interactions Flashcards
What % of human protein-coding genes have introns?
90%
What are the 3 main mutagenic mechanisms?
- Spontaneous mutation
- Mutagens
- Transposons
What are transposons?
Autonomously mobile DNA sequences that can excise from one region of the genome and insert themselves somewhere else
How many codons encode amino acids?
61
How can silent mutations reduce a phenotype?
The may swap a commonly used codon for a less commonly used codon - this may alter the rate of protein synthesis (most commonly slowing it down).
What are the two types of point mutations?
- Transitions
2. Transversions
What is a transition?
A point mutation that exchanges a purine for a purine or a pyrimidine for a pyrimidine.
What is a transversion?
A point mutation that exchanges a purine for a pyrimidine or a pyrimidine for a purine.
Which type of point mutation occurs easiest?
Transition
What is a nonsense mutation?
A point mutation that exchanges a codon for an amino acid into a stop codon.
What is a missense mutation?
A point mutation that exchanges a codon for an amino acid for a codon for a different amino acid.
What is a silent mutation?
A point mutation that exchanges a codon for an amino acid into a different codon for the same amino acid.
Aside from point mutations, what other changes are possible?
Insertion and deletions - INDELS.
Rearrangements - e.g. inversion, translocations.
Scrambling complex mutations
Duplications
What is a scrambling complex mutation?
Scrambling complex mutations are the name given to changes where the sequence is obviously different to the reference sequence but there has been nothing specific, no inversion, no duplication but it is clearly different.
What is the composition of a bipartite nuclear localisation signal?
2 basic amino acids, any 10 amino acids, 3/5 basic amino acids.
What are some uses of mutation?
- Natural - mutation gives genetic variation giving the capacity for adaptive evolution to deal with new environmental challenges.
- To the biologist - generating mutant alleles allows functions of an encoded protein to be determined.
Multiple alleles affecting differennt sites in the protein can give information about functional domains. - Combining several mutations allows us to look at the ordering of gene actions in genetic pathways and allows the determination of genetic interactions.
What is a dominant allele?
A dominant allele expresses its phenotypic effects whe heterozygous, most WT alleles are dominant.
What is a recessive allele?
The phenotype of a recessive allele is masked by the presence of a WT allele, most mutant alleles are recessive.
What are the 3 different types of dominant mutant allele?
- Hypermorph
- Neomorph
- Antimorph
What is a hypermorphic allele?
A mutant allele which produces a exaggerated version of the wild type allele, the phenotype is one of enhanced activity.
The phenotype of a hypermorph is worsed by increasing the WT gene dosage and is reduced by lowering the WT gene dosage.
What is a neomorphic allele?
A neomorph gives a new phenotype.
This is a mutation that causes a dominant gain of gene function different to the normal function e.g. ectopic gene expression or new protein activity.
Changing the WT gene dose has no effect on the phenotype of a neomorph.
How does changing the WT gene dosage affect the phenotype of a hypermorphic allele?
The phenotype of a hypermorph is worsened by increasing the WT gene dosage and reduced by lowering the WT gene dosage.
How does changing the WT gene dosage affect the phenotype of a neomorphic allele?
Changing the WT gene dosage has no effect on the phenotype of a neomorph.
What is an antimorphic allele?
Dominant mutations that act in opposition to the normal gene activity, AKA dominant negative mutations or anti-complementing mutations.
Increasing WT gene function reduces the phenotypic severity of an antimorph.
How does changing the WT gene dosage affect the phenotype of an antimorphic allele?
Increasing the WT gene dosage reduces the phenotypic severity of an antimorphic allele.
What are the 2 types of recessive mutant alleles?
- Hypomorph
2. Amorph/Null
What is a hypomorphic allele?
Partial loss of function, e.g. reduced gene expression or reduced protein activity. The phenotype of a hypomorphic allele is worsened when in trans to null allele compared to another hypomorphic allele (being homozygous). *Temperature sensitive recessive alleles are a specific class of hypomorph.
What kind of mutant allele is a temperature sensitive allele?
Hypomorph
What is a null allele?
Total loss of function, could be a deletion of the gene, could be an early STOP codon, either way gene expression is abolished and protein activity is eliminated.
What is the signature of a hypomorphic allele?
Gets worse when in trans to a deletion.
What are the phenotypic consequences (what alleles can be generated) as a result of a nonsense/frameshift mutation?
Null
Hypomorph
Dominant negative
How can a nonsense/frameshift mutation generate a null allele?
Introduction of a premature stop codon, the truncated protein is non-functional and likely eliminated by nonsense mediated mRNA decay.
How can a nonsense/frameshift mutation generate a hypomorphic allele?
Generation of a truncated protein that retains some function.
How can a nonsense/frameshift mutation generate a dominant negative allele?
Generation of a truncated protein that antagonises the normal function of a protein.
What are the phenotypic consequences (what alleles can be generated) as a result of a missense mutation or a small INDEL (of a mutiple of 3)?
Null
Hypomorph
Hypermorph
Dominant negative
How can a missense mutation or a small INDEL generate a null allele?
Mutation of a residue essential for protein function.
