gene mutations Flashcards
what are somatic mutations
occur in any cell of the body apart from germ cells (egg and sperm). cannot be inherited by offspring
what are germ-line mutations
occur in gametes (egg/sperm). is inherited by offspring
3 types of base-pair substitution mutation:
1. silent mutation
changes codon for an amino acid to another codon for that amino acid
no change in amino acid
3 types of base-pair substitution mutation:
2. missense mutation
changes codon for an amino acid to codon for another amino acid
change in amino acid
effect of missense mutations differ in severity -
neutral mutation - conservative amino acid substitution substitutes similar amino acid - less likely to alter function
eg. alanine for glycine
nonconservative amino acid substitution substitutes different amino acid - more likely to alter function
eg. glycine for glutamate
3 types of base-pair substitution mutation:
3. nonsense mutation
change codon for amino acid into stop codon (translation termination)
-premature termination of translation
mutation in 1st/2nd/3rd letter of codon is more likely to produce change in amino acid
1st
frameshift mutation -
addition or deletion of 1/more bases changes the reading frame and changes all amino acids downstream of the mutation
regulatory mutations alter
amount of protein produced by gene/amino acid sequence?
amount of protein product by gene NOT amino acid sequence
regulatory mutations affect regions (2)
- promoters and other regulatory protein binding sites
- intron boundaries - affects intron splicing in eukaryotes
what are promoter mutations
mutations that change consensus sequence nucleotides
-interfere with transcription initiation
-can reduce, enhance, or inhibit transcription
how is pre-mRNA processed
splicing to remove introns
what are splicing mutations
mutations that change nucleotides required for efficient splicing at intron-exon junctions
-can result in splicing errors and production of mutant proteins because introns are still there in mature mRNA
what are cryptic splice sites
some base-pair substitution mutations produce new splice sites that replace original splice spite during mRNA processing
-leads to new possible forms of protein product
origin of mutation - what is:
1. induced mutation
action of mutagen - environmental agent that changes nucleotide sequence
-mutagenesis - process of inducing mutations by mutagens
origin of mutation - what is:
2. spontaneous mutation
when there’s no known mutagen
-can be caused by errors in DNA replication
-important for evolution
types of spontaneous mutation
-DNA replication errors:
DNA pol can insert the wrong nucleotide
corrected by proof reading 3’ to 5’ exonuclease activity of DNA pol
trinucleotide repeat disorders - caused by
DNA pol slipping during DNA replication, increasing no. of trinucleotide repeats causes longer stretches of the same amino acid in the protein
-EXAMPLE - huntington’s disease
DNA nucleotide bases can spontaneously change to different structures called …. with slight differences in bonding and placement of hydrogen
tautomers
-amino (for adenine and cytosin) –> imino
-keto (for thymine and guanine) –> enol
what are transposable elements
found in genomes of all prokaryotes and eukaryotes
-can modify genomes and cause mutations on insertion into genes (rare in eukaryotes)
2 types of transposable elements
- DNA transposons - in both eukaryote and prokaryote genomes
- retrotransposons - in eukaryotes
both cause mutations by inserting into a gene and causing insertion mutation - BUT IS RARE IN EUKARYOTES
insertion sequences in E.coli
has a transposase gene bracketed by short repeat sequences
-transposase - moves IS element from 1 DNA location to another
-if IS element moves into a gene - big insertion mutation and mutant allele created which produces no active protein product
induced mutations are produced by
interactions between DNA and physical, chemical, or biological agents that generate mutations
DNA repair mechanisms - using correct base on the damaged DNA strand
-photoreactivation repair:
DNA damage repaired by photoreactivation enzyme (PRE) which cleaves the thymine dimer bond
in E. coli - photolyase enzyme
DNA repair mechanisms - using correct base on the damaged DNA strand
-base excision repair:
base specific DNA glycosylase
-uracil recognised as a noncomplementary base pair and replaced with complementary base (C)
DNA repair mechanisms - using correct base on the damaged DNA strand
-nucleotide excision repair:
repairs lesions which distort DNA eg. thymine dimers
human diseases can be caused by mutations in genes that encode proteins involved in …… …… mechanisms
DNA repair
-can cause hereditary cancer
a base-pair change that results in premature termination of translation is called a
nonsense mutation
what would result in a frameshift mutation
insertion of 2 bases
trinucleotide repeat disorders can result from slippage of DNA polymerase during DNA replication that results in increased trinucleotide sequence length. How many CAG repeats are needed for disease symptoms of Huntington’s disease?
> 36
