Topic 8A - Mutations and gene expression DVY * Flashcards
mutations cancer interpreting data on cancer stem cells regulation of transcription and translation epigenetic control of gene expression evaluating data on phenotypes
1
Q
what is a mutation?
A
any change to the a(nucleotide) sequence of DNA
2
Q
how can mutations be caused?
A
by errors during DNA replication
3
Q
how can the rate of mutation be increased?
A
mutagenic agents
4
Q
what are the different types of mutations?
A
substitution deletion addition duplication inversion translocation
5
Q
what is a substitution mutation?
A
one or more bases are swapped for another
6
Q
what is a deletion mutation?
A
one or more bases are removed
7
Q
what is an addition mutation?
A
one or more bases are added
8
Q
what is a duplication mutation?
A
one or more bases are repeated
GCCT –> GCCCCT
9
Q
what is an inversion mutation?
A
a sequence of bases is reversed
ATGCCT -> ACCGTT
10
Q
what is a translocation mutation?
A
a sequence of bases is moved from one location in the genome to another.
this could be movement within the same chromosome or movement to a different chromosome
11
Q
what does the order of DNA bases in a gene determine?
A
it determines the sequence of amino acids in a particular polypeptide
12
Q
what could happen if a mutation occurs in a gene?
A
the sequence of amino acids in the polypeptide that it codes for could be changed
genetic disorders
hereditary mutations
new alleles/ phenotypes - could be good or bad - essential for natural selection
13
Q
why is a change in the amino acid sequence of a polypeptide bad?
A
polypeptides make up proteins
a change in the amino acid sequence may change the tertiary structure of the protein, so it doesn’t work properly
e.g. changes enzyme’s active site so ES complexes can’t be formed
14
Q
what are genetic disorders?
A
inherited disorders caused by abnormal genes or chromosomes
some mutations can increase the likelihood of developing certain cancers
15
Q
what are hereditary mutations?
A
if a gamete containing a mutation for a genetic disorder or a type of cancer is fertilised, the mutation will be present in the fetus formed
16
Q
why do not all mutations have an affect?
A
the genetic code is degenerate so some amino acids are coded for by more than 1 DNA triplet.
particularly in substitution mutations, it won’t always result in a change in amino acid sequence
17
Q
which mutations always cause a change in the amino acid sequence?
A
additions, duplications and deletions
they change the number of bases in the DNA code
this causes a frameshift in the base triplets that follow, so triplet code is read differently
affects tertiary structure, non-functional polypeptide
18
Q
what are mutagenic agents?
A
things that can increase the rate of mutations e.g. UV radiation ionising radiation chemicals viruses
19
Q
how can mutagenic agents increase the rate of mutations?
A
acting as a base
altering bases
changing the structure of DNA
20
Q
how can mutagenic agents increase the rate of mutations by acting as a base?
A
chemicals called base analogs can substitute for a base during DNA replication, changing the base sequence in the new DNA
e.g. 5-bromouracil is a base analog that substitutes to thymine and pairs with guanine instead of adenine
21
Q
how can mutagenic agents increase the rate of mutations by altering bases?
A
some chemicals can delete or alter bases
e.g. alkylating agents add alkyl group to guanine, changing ts structure so it pairs with thymine instead of cytosine
22
Q
how can mutagenic agents increase the rate of mutations by changing the structure of DNA?
A
some types of radiation can change the structure of DNA, which causes problems during DNA replication
e.g. UV causes adjacent thymines to pair together
23
Q
what are acquired mutations?
A
mutations that occur in individual cells after fertilisation
24
Q
what happens if acquired mutations occur in genes that control rate of cell division?
A
it can cause uncontrolled cell division
this results in a tumour
25
what is a tumour?
a mass of abnormal cells
26
what are cancers?
tumours that invade and destroy surrounding tissue
27
what are the 2 types of gene that control cell division?
tumour suppressor genes
proto-oncogenes
mutations in these genes can cause cancer
28
what do tumour suppressor genes do?
they slow cell division by producing proteins that stop cells dividing or causes them to self destruct
29
what happens if a mutation occurs in the DNA sequence of tumour suppressor genes?
they can be inactivated
so the protein is not produced
the cells divide uncontrollably (rate of division increases)
resulting in a tumour
30
what do proto-oncogenes do?
they stimulate cell division by producing proteins that make cells divide
31
what happens if a mutation occurs in the DNA sequence of proto-oncogenes?
it becomes an oncogene
the gene can become overactive
this stimulates the cells to divide uncontrollably (rate of division increases)
resulting in a tumour
32
what are the 2 types of tumour?
malignant tumours
| benign tumours
33
what are malignant tumours?
cancers
usually grow rapidly and invade and destroy surrounding tissues
cells can break off the tumours and spread to other parts of the body in the bloodstream or lymphatic system
34
what are benign tumours?
grow slower than malignant, often covered in fibrous tissue that stops cells invading other tissues
often harmless, but can cause blockages and put pressure on organs
some can become malignant
35
how do tumour cells differ from normal cells?
they have an irregular shape
nucleus is larger and darker, sometimes more than one
don't produce all the proteins needed to function correctly
have different antigens
don't respond to growth regulating processes
divide by mitosis more frequently
36
what does methylation mean?
adding a methyl group onto something
37
what is methylation of DNA?
an important method of regulating gene expression - it can control whether or not a gene is transcribed and translated
38
what is hypermethylation?
when methylation happens too much
39
what is hypomethylation?
when methylation happens too little
40
why is hypermethylation bad?
when tumour suppressor genes are hypermethylated, they are not transcribed - so proteins to slow cell division aren't made
this means cells can divide uncontrollably and tumours can develop
41
why is hypomethylation bad?
hypomethylation of proto-oncogenes causes them to act like oncogenes - increasing production of proteins that encourage cell division
this stimulates cells to divide uncontrollably, which causes the formation of tumours
42
what affect can increased exposure to oestrogen have?
increase a woman's risk of developing breast cancer
43
what are the theories for why oestrogen increases the risk of breast cancer?
oestrogen can stimulate certain breast cells to divide and replicate
oestrogen is able to introduce mutations directly into DNA of certain breast cells
44
how does oestrogen stimulating breast cells to divide increase risk of breast cancer?
more cell divisions = increased chance of mutations = increased chance of cancerous cells
if cells become cancerous, rapid replication enhanced by oestrogen
45
what is a cancer risk factor?
something that increases a person's chance of getting cancer
| can be either genetic or environmental
46
what are genetic risk factors?
some cancers are linked with specific inherited alleles
| if you inherit that allele you're more likely to get that type of cancer
47
what are environmental risk factors?
exposure to radiation, lifestyle choices (smoking, alcohol consumption, high fat diet) have been linked to an increased chance of developing some cancers
48
how is knowing a mutation useful for it's prevention?
if a specific cancer-causing mutation is known, it's possible to screen for it in a person's DNA
knowing about increased risk means preventative steps can be taken to reduce it
knowing about specific mutations means that more sensitive tests can be developed, which can lead to earlier and more accurate diagnosis
49
how is knowing a mutation useful for its treatment and cure?
knowing how specific mutations cause cancer is useful for developing drugs to effectively target them
some mutations require more aggressive treatment , so understanding how mutation works can help produce the best treatment plan
gene therapy may be able to treat cancer caused by some mutations
50
what is gene therapy?
where faulty alleles in a person's cells are replaced by working versions of those alleles
51
what are multicellular organisms made up from?
they are made up from many different cell types that are specialised for their function
52
what are stem cells?
unspecialised cells that can develop into other types of cell
they can divide by mitosis to become new cells, which then become specialised
53
where are stem cells found?
in the embryo (become specialised cells to for a fetus) and in some adult tissues (become specialised cells that need to be replaced)
54
what are totipotent cells?
stem cells that can mature into any type of body cell in an organism
55
when are totipotent cells present in mammals?
in the first few cell divisions of an embryo, after this point the embryonic stem cells become pluripotent
56
what are pluripotent stem cells?
stem cells that can specialise into any cell in the body, but have lost the ability to become the cells that make up the placenta
57
what stem cells are present in adult mammals?
multipotent stem cells
| unipotent stem cells
58
what are multipotent stem cells?
they are able to differentiate into a few different types of cell
e.g. red and white blood cells can be formed from multipotent stem cells in bone marrow
59
what are unipotent stem cells?
they can only differentiate into 1 type of cell
| e.g. only divide to produce epidermal skin cells
60
how do stem cells become specialised?
all stem cells have same genes
some genes are expressed and others switched off
mRNA is only transcribed from specific genes which is then translated into proteins
61
how do the proteins that are translated in stem cells specialise them?
proteins modify the cell - determine cell structure and control cell processes
changes to the cell produced by these proteins cause the cell to become specialised. irriversibly
62
what are cardiomyocytes?
heart muscle cells that make up a lot of the tissue in our hearts
in mature mammals, it's thought that they can't divide to replicate themselves
63
how do hearts have regenerative capability?
old or damaged cardiomyocytes can be replaced by new cardiomyocytes derived from a small supply of unipotent stem cells in the heart
64
what are the theories on how quickly cardiomyocytes is being replaced?
- really slow process and some cardiomyocytes are possibly never replaced
- occuring more quickly, so every cardiomyocyte is replaced several times in a lifetime
65
what stem cell therapies already exist?
stem cells from the bone marrow can specialise into red or white blood cells and can be sued to replace abnormal blood cells to treat leukemia, lymphoma and SCID
66
what other treatments using stem cells are being researched?
spinal cord injuries - replace damaged nerve tissue
heart disease and damage caused by heart attacks - damaged heart tissue
bladder conditions - whole bladders grown and implanted
respiratory disease - donated windpipes
organ transplants - organs grow from stem cells
67
how can stem cells be used to treat respiratory diseases?
donated windpipes can be stripped down to their simple collagen structure and then covered with tissue generated by stem cells. this can then be transplanted into patients
68
what are the benefits of using stem cells in medicine?
they could save many lives
| they could improve the quality of life for many people
69
what are the 3 main potential sources of human stem cells?
adult stem cells
embryonic stem cells
induced pluripotent stem cells (iPS cells)
70
how are adult stem cells obtained?
from bone marrow in a relatively simple operation
| very little risk, lots of discomfort
71
what are the disadvantages of adult stem cells?
aren't as flexible as embryonic stem cells - can only specialise into a limited range of cells (multipotent)
72
how are embryonic stem cells obtained?
from embryos at an early stage of development
embryos created in a laboratory using IVF
stem cells removed at 4 - 5 days old and rest of embryo destroyed
73
what is IVF?
in vitro fertilisation - egg cells are fertilised by sperm outside the womb
74
what are the advantages of embryonic stem cells?
they can divide an unlimited number of times and develop into all types of body cells (pluripotent)
75
how are iPS cells created?
created by scientists in a lab by reprogramming specialised adult body cells to become pluripotent
76
how are adult cells reprogrammed to become pluripotent?
adult cells made to express a series of transcription factors that are normally associated with pluripotent stem cells.
this causes them to express genes associated with pluripotency
77
how can transcription factors be introduced to adult stem cells?
by infecting them with a specially-modified virus that has the genes coding for the transcription factors within its DNA
when virus infects adult cell, these genes are passed into the adult cell's DNA, meaning that the cell is able to produce the transcription factors
78
what ethical issues are there for using embryonic stem cells?
individual has right to life at moment of fertilisation
| if its fertilised by sperm it could be a fetus if placed inside a womb (so artificially activated dividing is ok)
79
why are iPS so good?
can be as flexible as embryonic stem cells, but obtained from adult cells so less problematic
could be made from patients own cells, so are genetically identical and could grow new tissue or organ
80
what controls the transcription of genes?
transcription factors
81
what do transcription factors do in eukaryotes?
move from cytoplasm to nucleus
where they bind to specific DNA sites near the start of their target genes
they control expression by controlling the rate of transcription
82
what are activators?
transcription factors that stimulate or increase the rate of transcription
83
what are repressors?
transcription factors that inhibit or decrease the rate of transcription
84
how can oestrogen affect transcription?
can bind to a transcription factor called an oestrogen receptor forming an oestrogen-oestrogen receptor complex
85
what does the oestrogen - oestrogen receptor complex do?
it moves from the cytoplasm into the nucleus where it binds to specific DNA sites near the start of the target gene
complex can act as an activator
86
what is RNA interference?
where small, double-stranded RNA molecules stop mRNA from target genes being translated into proteins. a similar process can occur in prokaryotes
87
what are the molecules involved in RNAi?
siRNA (small interfering RNA)
| miRNA (microRNA)
88
what does siRNA do?
in cytoplasm double-stranded siRNA associates with several proteins and unwinds
a single strand binds to target mRNA
base sequence of siRNA is complementary to base sequence in sections of the target mRNA
89
what do the proteins associated with siRNA do?
proteins associated with siRNA cut the mRNA siRNA is attached to into fragments - so it can no longer be translated
fragments move into a processing body, which contains tools to degrade them
90
what does miRNA do in plants?
the same thing that siRNA does in mammals
91
what does miRNA do in mammals?
it associates with proteins and binds to target mRNA in cytoplasm
miRNA-protein complex blocks the translation of the target mRNA
mRNA is then moved into a processing body, where it can be stored or degraded.
92
how specific is miRNA?
the miRNA isn't usually fully complementary to the target mRNA, so it is less specific than siRNA and so it targets more than 1 mRNA molecule
93
what happens to stored miRNA blocked mRNA
it can be returned and translated another time
94
what does epigenetic control do?
it can determine whether a gene is switched on or off
95
how does epigenetic control work?
through the attachment or removal of chemical groups (epigenetic markers) to or from DNA or histone proteins
96
what do epigenetic markers do?
they don't alter the base sequence of DNA
thye alter how easy it is for enzymes and other proteins needed for transcription to interact with and transcribe the DNA
97
why do epigenetic changes to gene expression occur?
play a role in normal cellular processes
| can occur in response to changes in the environment
98
how can offspring be affected by environmental changes that affected their parents?
most epigenetic marks on DNA are removed between generations, but some escape the removal process and are passed onto offspring
99
how can methylation of DNA be epigenetic control?
a methyl group attaches to the DNA coding for a gene at a CpG site
increased methylation changes DNA structure so that the transcriptional machinery can't interact with the gene - gene not expressed
100
what is a CpG site?
where a cytosine and guanine base are next to each other in the DNA (linked by a phosphodiester bond)
101
how can histones be epigenetically modified?
by the addition or removal of acetyl groups
102
what happens when histones are acetylated?
the chromatin is less condensed, so transcriptional machinery can access DNA, genes can be transcribed
103
what happens when acetyl groups are removed from the histones?
the chromatin becomes highly condensed and genes in the DNA can' be transcribed because the transcriptional machinery can't physically access them
104
what are histone deacetylase enzymes?
HDAC enzymes are responsible for removing the acetyl groups
105
what is fragile X syndrome?
an inherited duplication mutation duplicates CGG in a gene on the X chromosome
many more CpG sites for methylation, so it is switched off
can't produce protein it codes for
106
how can drugs be used to treat diseases caused by epigenetic changes?
epigenetic changes are reversible
increased methylation or decreased acetylation can switch genes off, drugs that stop methylation or inhibit HDAC can sometimes be used to treat diseases caused by these
107
what is the problem with developing drugs to counteract epigenetic changes?
these changes take place normally in a lot of cells, so it's important that the drugs are specific as possible
108
how are twin studies useful for determining what's due to environmental factors or genetic factors?
genetically identical twins - any difference in phenotype is due to environmental factors
if a characteristic is very similar in identical twins, genetics probably plays more of a role
109
what effect does a substitution reaction have on apolypeptide??
formation of stop codon - production stopped early - non-functional protein
forms different codon to code for different amino acid
forms codon that codes for same amino acid
110
how to regenerate new cells for plants?
scrape tissue sample from parent plant
place in agar growth medium containing nutrients and auxins
samples develop into tiny plantlets
plantlets planted into compost can grow into new clone plants
111
what stimulates a transcription factor to bind to DNA?`
a chemical binds to the receptor on the transcription factor
this causes the inhibitor to unbind
transcription factor can now bind to DNA to prevent protein synthesis
112
what is the epigenome?
All of the chemical modifications to all histone proteins and DNA in an organism
113
What is epigenetics?
Heritable changes in gene function
| Without changes to the base sequence of DNA
