Mechanisms and effects of mutations Flashcards
(23 cards)
Where can variation occur in the genome
In coding DNA
Single nucleotide polymorphisms
small insertions or deletions
Different number of repeats
micro-satellites (smaller)
minin-satellite (larger)
larger deletions and insertions
changes in the number or structure of chromosomes
What does variation lead to
normal human variation eye colour hair colour
differences in responses to medication (liver first pass metabolism)
influence the likelihood of getting diseases e.g Type II diabetes
Directly results in a genetic condition
What is a mutation
Permanent alteration or change in the genetic material that is harmful and occurs due to exposure to mutagenic agents or spontaneously through errors in DNA replication and repair.
What are examples of where you find non- harmful polymorphisms
sequence variation non functional DNA
sequence variation is within gene but does not change amino acid Silent
sequence variation changes amino acid but does not alter the protein function Missense
usually SNP’s
What is depurination? Endogenous or Exogenous
Endo cause of mutation
spontaneous fission of link between purine base and sugar resulting i loss of adenine or guanine from helix
loss of base incorrect nucleotides in new strand
What is deamination? Endogenous or exogenous?
Endo cause of mutation
cytosine deaminated to uracil
substitution of A instead of G in new strand
Reactive oxygen species
Endo or exogenous attack
endogenous attack
attacks purine and pyrimidine rings causing cleavage of DNA
Methylation of cytosines? Endo or Exogneous attack
Endo
occurs at GpG junction in the DNA
spontaneous conversion of 5methylcytosine to thymine
C substituted for T leads commonly to nonsense mutation (STOP codons)
accounts for 30-40% of point mutations
UV light? How does it mutate the DNA?
High exposure can cause cross likening of adjacent thymines to form thymine dimers.
Disrupts 3d Structure of DNA strands and therefore replication machinery
eventually excised strands resynthesised
Chemicals role in mutations
Interpolate DNA causing breaks and damage
ionising radition
causes breaks in DNA
What are germ line mutations
Mutations that occur in cells that produce the gametes mutations are passed into gametes and potential offspring
What are somatic mutations
mutations that occur in non germ-line tissues
passed onto all daughter cells
usually results in cancers
What naturally prevents mutations
Cell cycle checkpoints p53 at the G1/S checkpoint
DNA replication machinery
(proof reading ability can excise incorrect bases)
DNA mismatch repair mechanism
mispaired nucleotides may be left form replication and not picked up by DNA polymerase
mismatch protein complex recognises errors excises newly synthesised strand then resynthesises the strand using original template
How can damage by ionising radiation and chemicals be repaired?
Use maternal copy as a template strand to repair damaged chromosome
also be fixed by cutting and then rejoining ends via ligation leads to lots of changes
Last resort mechanisms
What are silent mutations
Affect coding DNA
single base substitution occur alters the genetic code but not the amino acid produced
no alteration in ppc produced
most frequent type of mutation and SNPs
What are Missense mutations
single base substitution mutation
results in coding of a different amino acid
if chemically similar biological activity and folding of protein may not be altered
If chemically dissimilar folding and therefore function of protein altered
What are nonsense mutations?
Substitution mutation
creation of a termination (stop) codon UAG, UAA, UGA
premature termination of translation non functional truncated protein
mRNA may be degraded before translation via nonsense mediated decay system
What is a splice site ?
introninc region of RNA that normally has the GU donor and AG acceptor sites that allow the binding of the splicosome and thus splicing of RNA to mRNA
What are splice site mutations?
Base changes in the intronic splice sites
prevents correct splicing leading to exon skipping and excision as splice site uses other donor acceptor site in adjacent region
altered protein
What are frameshift mutations?
Insertions and deletions
leads to frameshift all subsequent amino acid after point of insertion deletion effected
usually leads to premature formation of STOP codon
shortened non function ppc produced or mRNA may be degraded by a nonsense mediated decay system
What are copy number variant mutations
arrays of triplet repeats that are prone to expansion this can lead to disrupted gene function.
can mispair and cause deletions and insertions or expand and alter gene expression
e.g. Huntington’s CAG repeated well over the normal 11-34 times
Large scale deletions and insertions cause and effect?
unequal crossing over between repeat sequences
may effect one gene or a whole chromosome
effects dependant upon genes involved
