Polymorphisms and Mutations Flashcards
(67 cards)
1
Q
What is a mutation?
A
- change in genetic sequences
- can be a big change or a ingle base pair change
2
Q
There are different mutation types and different causes- What can these mutations lead to?
A
- dramatic impacts to phenotypes
- subtle changes
- or no change
- can be positive such as resistance or negative
3
Q
How frequent do mutations occur?
A
- trillions of cells in mammals body to changes is high
4
Q
Cells are exposed to mutagenic forces every hour - these can cause endogenous and exogenous changes.
What are examples of these mutants?
A
- UV damage = break DNA
- oxidative damage
- chemical mutagens
- Infections = retroviruses
- spontaneous DNA decay
- errors during DNA replication e.g. cancer in cells that have to replicate quickly
5
Q
DNA replication in mammal is very good at not making mistakes - what is the occurrence rate?
A
- only occurs on average 1 in 10 billion
6
Q
How many base pairs are in the cow genome?
A
- 3 billion base pairs
7
Q
In RNA viruses, the replication error of the RNA genome is far more common - what is the occurrence rate?
A
- 1 in 10,000
8
Q
What is advantageous about errors in RNA virus replication of RNA?
A
- this can be an advantage if they change antigens and invade adaptive immune response as they may not be as easily recognised or have antibodies against them
9
Q
There are two key aspects in reduction of mutations during DNA replication in eukaryotes - What are these?
A
- proof-reading DNA polymerases
- mismatch repair mechanism in DNA replication
10
Q
DNA polymerases are not just one protein - what is their structure?
A
- Quaternary structure with sub-units
11
Q
In mammal DNA how may DNA polymerases are there and what roles do they play?
A
- there are multiple DNA polymerases
- Play different roles in DNA replication
12
Q
What are the different roles of DNA polymerases?
A
- Some play a greater role in initiation of replication (Pol alpha)
- some more important in leading strand (pol epsilon) replication
- some lagging strand replication (pol beta)
13
Q
What is Polymerase gamma important in?
A
- important in mitochondrial DNA replication
14
Q
What does exonuclease activity allow for?
A
- the ability to identify a mistake and cut this out
- DNA polymerase has an exonuclease subunit that gives proof reading ability and allows it to cut out mistakes
15
Q
Even with proof reading exonuclease activity, DNA polymerases make an error - what is the occurrence of this?
A
- every 1 in 100,000 bases
- in a cow genome that is 30,000 mistakes per cell replication
16
Q
How can DNA polymerase errors be partly resolved?
A
- by mis-match repair mechanisms
17
Q
How do mis-match repair mechanisms work?
A
- need to identify mis-matched pairs
- insertion or deletion loops
- needs to fix these mistakes
18
Q
What are insertion or deletion loops?
A
- extra base e.g., addition of an extra A
- or deletion in a newly synthesised strand
19
Q
What molecules identify mis-match?
A
- range of enzymes named Mut
- MutL
- MutS
20
Q
What do endonucleases do in the mismatch repair mechanism?
A
- cut out wrong base
21
Q
What does polymerase beta do in the mis-match repair mechanism?
A
- heal over gap where exonucleases have cut
22
Q
What does DNA ligase do in the mis-match repair mechanism?
A
- sticks DNA back together
23
Q
Even with proof reading enzymes and mis-match repair mechanisms, what will still occur?
A
- mutations
24
Q
What are mutations the basis of?
A
- they are the basis of evolution
- therefore breeds, species, genetic diseases
25
What do all polymorphisms begin with?
- All polymorphisms began with a mutation
- a change in the base, specific allele
26
What is the general rule for polymorphism occurrence?
- polymorphisms are present in >1% of the population
27
Mutations can be changes where and to what?
- can be changes within the coding region of the gene (exons)
- or changes in introns, promotor, regulatory regions
28
What is one key reason for Texel sheep musculature?
- point mutation in 3' UTR (untranslated - pass stop codon in gene) of myostatin = impacts MiRNA post-transcription control
29
Why can mutations be advantageous?
- give a selective advantage and passed in to offspring
30
What do selectively neutral mutations lead to?
- no effect and are kept
- also known as silent mutations
31
What does deleterious do?
- decreases reproductive success either by increasing individuals susceptibility or predisposition to certain disease, disorder or impacting breeding outcomes
32
Mutations do not have a permanent classification - mutations can give advantages in different ..?
- time
- location
- tissue
- disease dependant
= generally an average
33
Mutations can be categories by what?
- small-scale mutations
34
Gives examples of small-scale mutations:
- base substitutions
- insertions
- deletions
35
What are base substitutions?
- single nucleotide polymorphisms (SNP)
- single base pair change
36
INDEL (insertion or deletion) is often in what?
- often in breeding
37
Small-scale mutations are often where?
- can be in coding regions
- promotors
- intronic regions
- regulatory regions
- non-gene related DNA
38
In the coding region (exons) these single nucleotide polymorphisms (point mutations) can be what and what do each impact?
- synonymous/non-synonymous
- missense/non-sense
- conservative or non-conservative
- lead to impacts in the phenotype
39
What is a synonymous mutation?
- not leading to a change in the amino acids
40
What is a non synonymous mutation?
- a change in the amino acid
41
What is missense?
- missense is when the codon changes to another amino acid codon
42
What is non-sense?
- non-sense is when it introduces a premature stop codon
43
What happens due to non-sense mutations leading to a premature stop codon?
- there is a truncated (smaller protein) missing amino acids encoded after the new stop codon
44
What can detect some nonsense mutations and where can it detect this?
- eukaryotic cells can detect this at the site of translation
45
What can eukaryotic cells detecting nonsense mutations lead to?
- can lead to nonsense mediated decay = no product so not protein gets produced
46
How does nonsense mediated decay work?
- proteins with the ribosome detect exon junction complexes (proteins)
- these are present upstream (- 20bp) of exon/exon boundaries
- added during RNA splicing
- if after the stop mRNA will be destroyed
47
For missense mutations, we can define the change depending on the relationship between what?
- the relationship between the original AA encoded and the new AA
48
What are the parameters for missense mutation definition?
- size
- charge
- functional impact
49
What is a conservative mutation?
- an amino acid replacement in a protein that changes a given amino acid to a different amino acid with similar properties
50
What is a non-conservative mutation?
- when the amino acid substitution involves two amino acids with very different chemical properties
51
In coding regions, insertion and deletions in multiples of 1 or 2 bp will lead to what?
- will lead to frame-shift mutations
52
What do frame-shift mutations lead to?
- all codons downstream of the insertion or deletion will not encode correctly
53
What happens if there are insertions of three?
- there are tolerated more often
54
There can be larger insertions and deletions what are examples of this?
- exons or whole genes being moved/duplicated
- gene copy differences between species common
55
What can gene duplication within species lead to?
- can lead to copy number variation
56
What is copy number variation?
- difference between individuals in copy numbers of specific genes
- more common than previously through
57
Mutations can also be large-scale mutations - what are examples of these?
- gene/region duplications
- chromosomal deletions
- chromosomal inversions
- chromosomal insertions
- chromosomal translocations
58
What can large-scale mutations play a big role in?
- speciation
59
What is aneuploidy?
- having missing or extra chromosomes
60
What are the common clinical features of a X monosomy?
- usually normal external genitalia
- abnormal oestrus or no clinical signs of oestrus
- small or hypoplastic ovaries
61
What does an X monosomy mutation cause and in what species?
- causes sterility in horses, cats and dogs, cattle and pigs
62
What are the clinical features of a xxx trisomy?
- normal eternal genitalia
- usually lack of clinical signs
- sone time irregular oestrus
63
What does a mutation in XXX trisomy cause and in what species?
- infertility in dogs and horses
64
What are the clinical signs of a mutation in XXY trisomy?
- small and hypoplastic testes
- abnormal spermatogenesis
- oligospermia or azoospermia
65
What does a XXY mutation cause and in what species?
- sterility in cats and cattle dog and horse and pig
66
What are the clinical signs of a XYY trisomy?
- usually normal phenotype
- small testes
67
What does a XYY trisomy cause and in what species?
- infertility in cattle
