Mechanisms and effects of mutations

Question 1

Where can variation occur in the genome

Answer 1

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

Question 2

What does variation lead to

Answer 2

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

Question 3

What is a mutation

Answer 3

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.

Question 4

What are examples of where you find non- harmful polymorphisms

Answer 4

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

Question 5

What is depurination? Endogenous or Exogenous

Answer 5

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

Question 6

What is deamination? Endogenous or exogenous?

Answer 6

Endo cause of mutation

cytosine deaminated to uracil
substitution of A instead of G in new strand

Question 7

Reactive oxygen species

Endo or exogenous attack

Answer 7

endogenous attack

attacks purine and pyrimidine rings causing cleavage of DNA

Question 8

Methylation of cytosines? Endo or Exogneous attack

Answer 8

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

Question 9

UV light? How does it mutate the DNA?

Answer 9

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

Question 10

Chemicals role in mutations

Answer 10

Interpolate DNA causing breaks and damage

Question 11

ionising radition

Answer 11

causes breaks in DNA

Question 12

What are germ line mutations

Answer 12

Mutations that occur in cells that produce the gametes mutations are passed into gametes and potential offspring

Question 13

What are somatic mutations

Answer 13

mutations that occur in non germ-line tissues
passed onto all daughter cells
usually results in cancers

Question 14

What naturally prevents mutations

Answer 14

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

Question 15

How can damage by ionising radiation and chemicals be repaired?

Answer 15

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

Question 16

What are silent mutations

Answer 16

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

Question 17

What are Missense mutations

Answer 17

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

Question 18

What are nonsense mutations?

Answer 18

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

Question 19

What is a splice site ?

Answer 19

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

Question 20

What are splice site mutations?

Answer 20

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

Question 21

What are frameshift mutations?

Answer 21

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

Question 22

What are copy number variant mutations

Answer 22

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

Question 23

Large scale deletions and insertions cause and effect?

Answer 23

unequal crossing over between repeat sequences
may effect one gene or a whole chromosome
effects dependant upon genes involved