Cell Physiology - Mutation Lecture Flashcards
What is a mutation?
A randomly produced, permant heritable change in the genes of an organism
Mostly arise in DNA synthesis
Name the different types of mutatuions
Point mutations (affect a single nucleotide) - Base-pair substitutions and frameshift mutations
Macrolesions (alterations in chromosome # or structure)
Deletion, Insertion, inversion, rearrangement/translocation (chromosomal), , substitution
Base-Pair Substitutions
One base pair is substituted out for another base pair
Could cause no change if the same amino acid is coded for
Could cause little change if an amino acid of similar prperties is coded for (i.e. hydrophobic nature)
Could cause a lot of change depending where the mutation occurs (at the active site of an enzyme)
Could also cause a lot of change if a sense codon is changed into a nonsense (stop) codon = production of protein is ended prematurely)
2 types:
Transition (substitution of a purine for a purine and a pyrimidine for a pyrimidine = less effect)
Transversion (substituion of a purine for a pyrimidine and vice versa) = more severe effect
Frameshift Mutation
Addition or deletion of 1, 2, or 4 nucleotide pairs
Changes the reading frame of the RNA = dramatic change
Could cause a protein coding to end prematurely (b/c it is likely a stop codon would be reached before it should = truncated protein)
NOT framshift if there is an addition or deletion of 3 nucleotide pairs = does not change the reading frame; cna cause mild or severe effects depending on where the mutation occurs in the protein
Macrolesions
Severe altrations such as translocations, inversions, deletions, insertions causing a change in the chromosome structure (deletion or insertion of >4 bases)
Aneuploid and euploid variations causing change in the chromosome #
Deletion of a whole chromosome = typically negative
Addition of a whole chromosome = usually causes genetic toxicity syndrome (ex - Trisomy 21)
Insertion Mutation
Addition of one or more nucleotide pairs into a DNA sequence (often due to slipping of DNA Polymerase)
Can also occur as the addition of a larger sequence into a chromosome (caused by unequal crossover in meiosis)
Addition of a whole chromosome can cause genetic toxicity syndrome
Effect is location-dependent:
Insertion at an intron = very little effect
Insertion at an exon = bigger effect
If insert b4 promotor = no effect b/c not within the reading frame of the gene
If insert after the promotor = bigger effect b/c within the gene
Effect is also dependent on the number of base-pairs:
framsehift vs non-frameshift mutations
Deletion Mutation
Loss of genetic material
Deletion of one or more nucleotide pairs into a DNA sequence
Can also occur as the deletion of a larger sequence into a chromosome (caused by unequal crossover in meiosis)
Deletion of a whole chromosome can also occur
Effect is location-dependent:
Deletion at an intron = very little effect
Deletion at an exon = bigger effect
If delete b4 promotor = no effect b/c not within the reading frame of the gene
If delete after the promotor = bigger effect b/c within the gene
If delete enhancer = decrease in RNA and protein
If delete promotor = No RNA or protein
Effect is also dependent on the number of base-pairs:
framsehift vs non-frameshift mutations
Inversion Mutation
A DNA sequence in reverse order
Location dependent:
If inverted at exon = little effect b/c the reading frame is unaffected
If inverted at the enhancer = no effect
If inverted at the promotor = no RNA or protein
Creation of a premature stop codon from inversion can also occur
Chromosomal Rearrangement
Translocation = a chromosomal segment is attached to a new location in the chromosome
Caused by rearrangmwents of parts between nonhomologous chromosomes
Causes disease
Substitution Mutation
Replacement of one nucleotide in a DNA sequence by another nucleotide OR replacement of one amino acid in a protein by another
3 Types:
Synonomous Substitution - Silent
Nonsynonomous Substitutions - Missense and Nonsense
1 base-substituion in either the enhancer or promotor = little effect
Silent Substituions
No change in phenotypic expression
Caused by:
Change within a noncoding region (intron)
Change with in an exon that causes no replacement of the amino acid in question (i.e. one amino acid is coded for by numerous codons) = Synonomous Substitution
Missense Substitutions
A nonsynonomous substitution
A substituion codes for a different amino acid
Conservative - Change to an amino acid of similar properties
Nonconservative - Change to an amino acid of different porperties = can render to protein nonfunctional or different = causes disease
Nonsense Substitution
A nonsynonomous substituion
A substitution that causes the appearance of a premature stop codon (UAA, UAG, UGA) = truncated protein
If a promotor is relocated = ?
Could cause cancer b/c it could allow for the coding of cancerous genes
The DNA code is degenerate = ?
One amino acid can be coded for by more than one codon
