MCBG ESA1 Flashcards
1
Q
what is heterochromatin and where is it found?
A
- Tightly packed DNA, in the form of 30nm solenoid.
- The information is not available for trasncription machinery.
- Found in nucleus periphery and telemoeres and centromeres are made of heterochromatin.
2
Q
What is euchromatin and where is it found?
A
Euchromatin is loosely packed DNAin the form of “beads on a string”, thus available for transcription.
It is found centrally in the nucleus.
Constitutes 92% of the genome.
3
Q
What is smooth ER? Functions? In which organs is it abundant?
A
Smooth ER is ER without ribosomes. Tubular in shape.
- responsable for lipid and steroid manufacture
- found in liver, mammary glands, testis, ovaries and adrenal glands.
4
Q
What do free ribosomes synthesise?
A
Proteins destined for cytoplasma, or post-translational insertion into
- mitochondria
- nucleus
- perioxysomes
5
Q
Proteins synthesised by ER-bound ribosomes are destined for…?
A
- secretory pathway (vesicles)
- plasma membrane insertion
- lysosomes
6
Q
Peroxysomal function?
A
Detoxification by oxidation; abundant in the liver.
7
Q
In what are mitochondria of steroidogenic cells different?
A
they are more tubular in shape
8
Q
Actin filaments:
- general function
- size
- where in the cell?
A
Actin filaments are
- helical
- cortical distribution in cells and in microvilli
- 5-9 nm in diameter
- found in microvilli of a brush border (eg. small & large intestines)
9
Q
Intermediate filaments
- size
- general function
- where is the cells?
- associated pathology
A
intermediate filaments
- 10 nm diameter
- often linked to desmosomes so involved in cell adhesions, and also beneath inner nuclear membrane
- desmosomes are on lateral cell surfaces
- abundant in skin
- eg. keratin, vimentin
- keratin associated with Epidermis Bullosa (= ++ blistering)
10
Q
Microtobules
- size
- general structure
- general function
- where in the cell?
A
Microtubules
- 25 nm diameter
- made of tubulin
- microtubules often oragnised in 9 doublets + 2 central singlets, in cilia and flagella
- involved in movement of cilia and flagella, and transports of NTs inside neural cell
- found at/in motile sites and phases: interphase, anaphase, …
11
Q
What indicates the 5’ end of DNA molecule?
A
5’P
12
Q
What indicates 3’ end of DNA?
A
3’OH
13
Q
What indicates 3’ end of RNA molecule?
A
3’OH
14
Q
What differenciates the pentose sugars of RNA & DNA ?
A
RNA has 2’OH
DNA has 2’H
15
Q
How many rings does a purine have, what bases are purines
A
Purines = 2 rings = A & G
16
Q
How many rings do pyrimidines have and which bases are pyrimidines?
A
Pyrimidines = 1 ring = C & T
17
Q
Which bases can make 2 H bonds between them?
A
A and T
18
Q
Which bases can make 3 H bonds between them?
A
C and G
19
Q
What is a nucleotide?
A
Base + pentose sugar + phosphate
20
Q
What is a nucleoside?
A
Base + pentose sugar
21
Q
Conventionally, in which L to R direction is a strand drawn?
A
top strand is 5’ to 3’
22
Q
What is the hierachy of DNA packaging?
A
- Nucleosomes = DNA around histone proteins; the whole structure is called beads on a string (euchromatin’s form)
- 30 nm Solenoid = 6 nucleosomes per level, form a cork-screw (heterochromatin’s form)
- Solenoid loops
- Chromatid
23
Q
What are the phases of mitosis, and what happens during each one?
A
Prophase = Condensing Prometaphase = nuclear enveloppe disappears &chromosomes are attached to the spindle Metaphase = align on plate, alignment is RANDOM Anaphase = pulled apart, each sister chromatid becomes a chromosome Telophase = nuclear envelope reforms
24
Q
What is comprised in the Initiation phase of DNA replication? (Prokaryotes)
A
- Origin of replication recognition (plasmids)
- Recruitment of DNA polymerase and proteins
- Primase (type of RNA polymerase) synthesises a primer so that DNA polymerase has a 3’ end to elongate
25
What is a primase and in what process is it involved?
Primase is an RNA polymerase, synthesises primer in DNA replication.
After elongation, the RNA primer will be removed by a 5' to 3' exonuclease.
26
What occurs during the Elongation phase of DNA replication? (Prokaryotes)
1. Helicase unwinds
| 2. DNA polymerase adds on nucleotides 5' to 3', giving rise to a leading and a lagging strand (Okazaki fragments)
27
What is the Termination phase of DNA replication? (Prokaryotes)
Because the DNA is circular (plasmid) there will come a point when leading and lagging meet. Then DNA ligase joins the fragments.
28
What are the 3 types of DNA replication stress, ie. causes of DNA replication errors?
1. Machinery defects
- slippage: looping of one of the strands, inducing deletion or insertion of bp in the new strand.
- Proofreading defect: nucleotide misincorporation is normally corrected by DNA poymerase proofreading (exonuclease 3' to 5') but if there is a proofreading defect, then error persists.
2. Factors Hinder replication fork progress (DNA lesions, repetitive DNA ribonucleotide incorporation)
- single strand breaks SSBs: they persists if base excision repair BER is faulty
- double strand breaks DSBs: they persist if defects in BRCA
3. Defect in resolution pathways (= inefficient correction of mistakes)
29
What are microsatellites? Why are they clinically relevant?
Microsatellites are di-, tri-, or tetra nucleotide repeats in DNA sequences. Microsatellites have a higher mutation rate thatn other areas of DNA.
Microsatellites are often in non-coding regions, and no not have any specific function, therefore cannot be selected against. this allows them to accumulate mutations unhindered over generations and gives rise to VARIABILITY which can be used for DNA FINGERPRINTING and IDENTIFICATION purposes.
But. microsatellites can also be found in coding regions, and gives rise to diseases such as Huntingtons.
Huntingtons:
- death of brain cells, lack of coordination, unsteady gait, ...
- autosomal dominant
- the number of CAG trinucleotide repeats is highly relevant to the severity of disease.
at each generation, the number of repeats increase and the age of onset becomes earlier.
30
What is the difference between Preprocollagen and Procollagen, and where does the differenciation occur?
Preprocollagen has a SIGNAL SEQUENCE
Procollagen does NOT have a signal sequence anymore.
The signal sequence is cleaved off Preprocollagen in the ER.
31
Under which precursor form is collagen secreted from fibroblasts?
procollagen
32
what is tropocollagen?
unit of collagen
made from procollagen triple helices.
it does not have the non-coiled ends.
33
what is procollagen?
- it is a precursor building block of collagen secreted by fibroblasts.
- it is a triple helix 2 a1chains + 1 a2 chains, with its N-term and C-term ends NOT coiled
- it will then assemble into tropocollagen (non coiled ends cut off by procollagen peptidase)
34
what happens to procollagen before it can assemble into tropocollagen? which enzyme is responsable for this?
The non-coiled ends of procollagen triple helix are cleaved off by procollagen peptidase.
35
How does tropocollagen assemble as collagen? Where does this occur? which enzyme is responsible?
Tropocollagen molecules assemble by cross-linking which occurs outside the fibroblast thanks to enzyme Lysyl oxidase
36
What is the difference between preproinsulin and proinsulin? Where does this differenciation occur?
Preproinsulin has a signal sequence that is cleaved off in ER to give proinsulin.
37
What are the characteristics of insulin's disulphide bonds?
Insulin can be thought of as 3 chains in series A-B-C.
when disulphide bonds form, 2 will occur between chains A & C, and 1 inside the C chain (C-C).
The disulphide bonds between A and C induce curving of the molecule so that A and C are opposite.
In the Golgi, endonucleases will make 2 cuts and excise B chain. This is now insulin! it is packed into zymogen granules and waits for signal to be released.
38
What is the most abundant protein in the body?
Collagen
39
3 major characteristics of collagen are...
- every 3rd aa is Glycine (in each of the 3 chains)
- triple helix: 2a1 + 1a2
- hydroxylated lysine and proline
40
What is osteogenesis imperfecta? Symptoms?
Type I collagen mutation giving rise to a poor quality collagen.
Symptoms can be: Blue sclerae, fracture follow only light trauma, other family members affected (autosomal dominant)
41
Why do people with collagen defects have blue sclerae?
The sclerae is particularly thin, so choroidal veins are showing through them.
42
What does the banding pattern of collagen look like when treated with SDS-PAGE.
2 bands:
- 1 for the 2 a1 molecules => thicker because 2 molecules
- 1 for the a2 molecule
Indeed, SDS unfolds, and 2-mercaptoethanol breaks disulphide bonds.
But if a mutation inserts an extra Cysteine, then extra disulphide bonds could form, and migration on gel would be affected.
43
What shape binding curve does haemoglobin have?
Sigmoidal. this confers it its diferent binding properties at different ppO2, thus different binding affinities in different tissues.
44
what shape is myoglobin's binding curve?
Hyperbolic
45
How many chains and haems does haemoglobin have?
4 chains, 4 haems.
| HbA, 2 chains are a, 2 chains are b
46
What chains does foetal haemoglobin have?
2a and 2y
47
What two states can Haemoglobin be found in and what are the differences between the two?
1. R state = relaxed, high affinity, low release (lungs!)
| 2. T state = tense, low affinity, high release (tissues!)
48
What haemoglobin state does oxygen binding favor and what is this phenomenon called?
O2 binding favors R state (the high affinity, low release state)
= allosteric cooperativity
49
What haemoglobin state does a low pH favor?
Low pH = tissues, so we want O2 release, so favors T state
50
What happens is carbon monoxyde binds to haemoglobin? Why is this a problem?
CO binds 250x better to Hb than O2 does, and promotes R state. Becasue of it's very high affinity, it will never let go, and so O2 will never be able to be transported by this haem. basically like loosing Hb.
51
Structurally, how is the haem of myoglobin held in place?
held in the middle of the protein by histidine 93 of the 8th a-helix.
52
what percentage of myoglobin is a-helical?
75%
53
What is the general definition of a thalassaemia?
imbalance in the ratio of a:b chains of haemoglobin. (should be 1:1 as each HbA has 2a + 2b
54
a-thalassaemia, what is it, when does is occur, what are the symptoms?
a-thalassaemia is a defects in a-chain synthesis.
It will appear before birth at foetal Hb also has a-chains.
anemia, yellow sclerae, palpable spleen, hypochromic RBCs.
55
what is b-thalassaemia? + symptoms
b-chain of HbA defect. will only appear after birth, as there is no b chain in HbF (foetal).
symptoms:
- yellows sclerae (colour comes from bilirubin, bilirubin is produced by RBC breakdown, and in thalassaemias, RBC breakdown is high)
- palpable spleen: because of misshapen RBCs get stuck, and cause inflammation. also, if haemoglobin levels drop too much and bone marrow can't produce replacement fast enough, then spleen will also produce blood cells = extramedullary erythropoeisis.
- hypochromatic RBCs, variable shape and size, reticulocyte presence & RBCs with inclusion bodies: inclusion bodies are aggregates of chain that there is an excess of. ie. if b chain defects, then a-chains will aggregate = inclusion bodies.
56
what is alkaptonuria? (inheritance mode, symptoms, affected enzyme)
Alkaptonuria is an enzymatic defect of HOMOGENTISIC ACID OXIDASE, Causing accumulation of homogentisic acid.
It's mode of inheritance is autosomal recessive.
main symptom: black urine due to the homogentisic acid.
57
What is phenylketonuria? (affected enzyme, mode of inheritance, consequences)
- Phenylketonuria is a defect in PHENYLALANINE HYDROXYLASE (PAH gene), causing build up of phenylalanine in blood and brain.
- Mode of inheritance is autosomal recessive.
- most common mutation is arginine to tryptophan at position 408
- Consequences: seizures, intellectual disability, etc.
58
What is albinism?
Albinism is an autosomal recessive condition in which patients lack skin pigmentation, ie. no melanin production.
It is an enzymatic defect of TYROSINASE that normally converts hydroxyphenylpyruvic acid into DOPA, then dopa will be converted on to melanin.
59
What do Alkaptonuria, phenylketonuria and albinism have in common?
They are all autosomal recessive conditions in which an enzyme is affected.
60
After what sort of event does mosaicism normally occur?
After non-disjunction.
(But not in 1st post-zygotic division; or cell lines will be normal!)
Only in subsequent divisions will non-disjunction lead to mosaicism, with some lineages having 47 chromosomes and some with 46.
61
What can non disjunction in mitosis cause (not in 1st post zygotic division, but subsequent mitotic events)?
Mosaicism some 46 chr. lineages, some 47 chr. lineages
62
What does non-disjunction in meiosis cause? If in meiosis I, and if in meiosis II?
Aneuploidy!
- if in meiosis I: all gametes are wrong (47,47,45,45)
- if occurs in meiosis II: 2 gametes are wrong (47&45), and 2 are ok.
63
What is the most common cause of polyploidy?
Polyspermy
64
What is the most common cause of aneuploidy?
Meiotic non-disjunction
65
Why is aneuploidy different from anaphase lag?
because in aneuploidy, no chromosomes are actually destroyed, they are just not equitably sent into cells.
In anaphase lag, the chromosome that fail to attach to the spindle and is left behind is not integrated into any cell, it is destroyed!
66
What is a very useful application of cytogenetics (ie. study of genetic cellular contitution through visualisation and analysis of chromosomes)?
Prenatal diagnosis, birth defects, infertility, and acquired abnormalities (leukaemias, solid tumours, etc.)
67
What are 2 common invasive prenatal diagnosis methods?
1. Amniocentesis: amniotic fluid sampling from 15 wks+, 0.8% miscarriage risk
2. Chorionic Villus Sampling: sample of placenta is taken by sucction and then karyotyped. available 11-12 wks+ and has a 1.2% risk of miscarriage.
68
What sort of non-invasive technique can be used prenatally?
Maternal serum screening. Not actually a diagnostic tool, if screening is positive then do invasive.
Maternal serum can be used for Downs screening.
69
What are the units of Vmax in the context of enzymes kinetics?
units of RATE (mmol/sec, etc)
70
What are the units of Km in the context of enzyme kinetics?
units of concentration
71
What is Km?
Km is the concentration of subsate needed to achieve half of Vmax.
72
What is Vmax?
Vmax is the maximum velocity of an enzyme
73
What sort of inhibitor affects Km but not Vmax?
Competitive inhibitor. Its effect can be outcompeted by increasing the concentration of substrate.
74
What sort of inhibitor affects Vmax but not Km?
A non-competitive inhibitor. it will not bind to active site but a different place on the enzyme. This will make the enzyme less effective.
75
What is a lineweaver-burk plot?
It makes hyperbolic curves linear.
It is drawn by using 1/V and 1/[S] as axis'.
The slope is then Km/Vmax
1/Km is found at the intersection of the x-axis
1/Vmax is fiund at the intersection of y-axis
76
What is a missense mutation?
New sequence codes for a different amino acid
77
What is a nonsense mutation?
The new sequence codes for a STOP codon
78
What are the stop codons? (3)
UAG u are gone
UGA u go away
UAA u are away
79
What is a synonymous mutation?
codes for the same aa, even though codon had changed. this can occur because the code is degenerate.
80
What are silent mutations?
A muation is silent if it is synonymous but also if it is in a non-coding & non-functional part of the genome.
81
In the context of mutations, what is a transition?
purine to purine
| pyrimidine to pyrimidine
82
In the context of mutations, what is a transversion?
purine to pyrimidine
| pyrimidine to purine
83
What are trasnposable elements?
They are jumping sequences of DNA, longer than a gene.
They are always contained within other DNA molecules, never free form, but they do not have a specific position in the genome. They move to random site within the genome with the following possible consequences:
- TE jumps to non-coding sequence: no effect
- TE jumps into an exon: gene inactivation
- TE jumps into a promoter: transcription could be activated in a cell where it shouldn't be.
84
Huntingtons: what is this disease, and at which "point" does it declare?
It is a neurodegenerative disease.
Autosomal dominant.
Triplet CAG repeats = microsatellites
- normal if 6 to 39 repeats
- disease 35 to 121
The more repeats there are the more prone people are to accumulate replication mistakes
The more repeats there are, the more prone one is to the disease, and the earlier the age of onset will be.
Through generation, the no of repeats increase, and the age of onset get earlier.
85
What are progeroid syndromes?
They are rate genetic syndromes that mimic ageing.
Eg. Werner Syndorme, autosomal recessive
- mutation in WRN gene, Werner protein is a Helicase.
- Werner defects lead to replication errors & damage
- patients show normal signs of ageing but a lot sooner.
86
"What is cancer?" brief, and mutation orientated...
Cancer is an accumulation of mutations. DNA replication stress is a major source of mutations (repl. machinery defects, factor hindering repl. fork progression, repair mechanism defects)
The first mutaitons normal induce hyperproliferation, eg APC gene mutation.
K ras mutation
DCC mutation
P53 mutation = CARCINOMA. P53 is a. ery improtant gene in cancer. When cells lose p53, they are then majorly prone to cancer.
87
What is P53?
P53 is a very improtant gene involved in cancer.
Indeed it is a TUMOUR SUPPRESSOR.
Often called the "guardian of the genome" for its function in preventing mutation.
88
What is non-homologuous end joining and when is it appropriate?
It is a quick, simple easy method or rejoining a DNA molecule when broken.
It is very active in our cells, but can lead to errors because the break in strands may not be neat inducing basepair loss.
89
3 sorts of homology directed DSB repair
1. Single-stranded annealing - pbl, loss of sequence
2. Synthesis-dependent strand annealing: one strand invades (ideally) sister chrimatid double strand, and copies the missing segment. No information loss. Need exonuclease, DNA polymerase and ligase. Produces NON-crossover products.
3. Double-stranded break repair: BOTH broken strands invade sister chromatid. = DOUBLE TEMPLATING. At end of this process strands are interlinked, and need cleaving for release. the site where in ading and displaced strands cross is called HOLLIDAY JUNCTION. Can produce cross-over or non-crossover products depending on where the cutting takes place.
90
What is the repair mechanism for pyrimidine dimerisation, ie bulky DNA adducts?
Nucleotide excision repair.
1. recognition
2. endonuclease dual incision on single strand
3. DNA polymerase
4. Ligase
91
What is the repair pathway for deamination, abasic sites and single-strand breaks?
Base excision repair.
1. DNA glycosylase: takes away the sugar
2. AP endonuclease (apurinic/apyrimidinic): takes away the backbone segment
3. Deoxyribosephosphodiesterase
4. DNA polymerase
5. Ligase
92
What is the correct repair pathway for mismatches, insertions or deletions?
Mismatch repair MMR
1. Endonuclease 3' to 5' (removes up to 2000 bases single strand
2. DNA polymerase replaces removed bases
3. Ligase
If problem with mismatch repair, then
- Lynch syndrome
- Colorectal cancer
93
What are the correct pathways for double strand break repair?
1. Non-homologuous
- non-homologuous end-joining
2. Homologuous
- SSA Single Strand Annealing: cut back to complementary sequences, then join. Loss of information
- SDSA Synthesis-dependent strand annealing: cut back, invasion of one end into sister chromatids (relevant before mitosis seeing as need the sister!) Produces non-crossover products.
- Double stranded break repair DSBR: cut back, then BOTH strands invade. Need to cut at holliday junctions. depending on cut will produce croos-over products or not.
94
What is the designation for eukaryotic Ribosomes?
80S (40S & 60S)
95
What is the denomination for prokaryotic ribosomes?
70S (30S + 50S)
96
What are the characteristics and an example of rRNA.
- Ribosomal
- 80% of all RNA
- only a few types, but many copies
- Eg. RNA polymerase I
97
What are the characteristics and example of mRNA?
- messenger
- 2% of all RNA
- many different types, but only a few copies of each
- Eg. RNA polymerase II
98
What are the characteristics or tRNA?
- Transfer
- 15% of all RNA
- single stranded molecule that forms clover shape (loops) but H binds forming between complementary and antiparallel sequences contained
- ADAPTOR between RNA and amino-acids, essential for translation
- the 1st tRNA of translation will always be a Methionyl tRNA
- tRNAs are charged with an aa corresponding to their anticodon by AMINOACYL-tRNA synthetase using ATP.
99
What is a wobble base?
It is the 5' base of the anticodon and the 3' base of the codon. It allows 1 same tRNA to recognize more than 1 codon!
Anticodon base I can recognize A/C/U
100
What is a reciproqual translocation?
- 2 break rearrangement
- 2 fragments break-off ans SWAP positions
- usually unique to a family
- can be balanced or unbalanced gametes produced by carriers
a) Balanced: no material is lost, gametes OK
b) Unbalanced: loss of material, gametes not ok. Offspring will have abnormal phenotype.
101
What is a robertsonian translocation?
- 2 accrocentric chromosomes FUSE
- often 13, 14, 15, 21, 22
Chrimosome count often 45. so trivalent is formed at meiosis (= unstable)
102
What is specifically targeted by penicilin?
Penicilin targets the CELL WALL, eukaryotes don't have one so not affected. Bacterial integrity is damaged.
103
What is it and what does tetracyclin specifically target?
Tetracyclin is an antibiotic, is targets subunit 30S, eukayotic ribosomes have 40S and 60S subunits, so not affected. In inhibits the association of aminoacyl-tRNAs with the A site of the bacterial 30S subunit.
104
What are the different functions of ribosomal subunits (eukaryotes)?
The small subunit monitors the complementarity between tRNA anticodon and mRNA, while the large subunit catalyzes peptide bond formation
105
Which are the different functional sites of the ribosome and what occurs in each of them?
```
A = arrival site, closest to 3' end of mRNA, it is the site at which aminoacyl-tRNAs arrive.
P = has a tRNA that will attach its aas to the new aa in A site (old one add on top of the new one)
E = exit site, wheree the tRNA that had transferred its aa leaves.
```
106
What is Aminoacyl-transferase, what does it do?
It is an enzyme implicated in polypeptide chain elongation during translation. It is the enzyme that joins aminoacids with eachother in the P site of the ribosome.
107
what is aminoacyl-transferase?
It is an important enzyme of translation. It charges tRNAs with an amino acid using ATP.
108
2 mathematical definitions of pH?
pH = - log[HCO3]
pH = pKa + log ([A]/[AH])
109
How does 2,3-BPG influence O2 binding to haemoglobin?
2,3-BPG is increased in people living at altitude. It favours O2 release by haemoglobin, ie. encourages low affinity, high release, so T state.
110
What happens to pH when we hyperventilate?
We get rid of more CO2, so pH increases.
111
What is TATA Box
It is part of the promoter indicating where translation should occur from. It is on the coding strand (ie not the template)
112
By which organelle are lyosomes generated?
the golgi
113
What is achondroplasia?
- common cause of dwarfism
| - overactivity of negative regulator on bone growth.
114
What gene is most commonly affected by Cystic fibrosis? What is this mutation? What imct will it have?
dF508 is most commonly mutated and suffers a 3 nucleotide deletion.
This results in loss of phenylalanine in the 508th position on the protein. This protein won't fold properly and is consequently not appropriately inserted into the membrane.
115
What is sickle cell anaemia?
It is an autosomal recessive disease affecting b-globin gene HBB. The mutation is a transversion from A to T in the 7th codon but the 6th amino acid! This results in a Glu to Val. Val is hydrophobic.
116
What is the "end replication problem" and by what is it solved?
The primer for the final Okazaki fragment will have nowhere to settle against. So without a solution, the DNA will get shorter at every replication event = problem
Telomerase solves the problem by synthesizing a repetitive DNA sequence opposite which primase can deposit a primer. telomeres get shorter and shorter with each replication. When they get too short, cells go into senescence (or apoptosis).
117
What is Xeroderma pigmentosa?
It is a rare autosomal recessive disease that affects DNA repair, in particular nucleotide excision repair.
But nucleotide excision repair is essential in resolving pyrimidine dimers that occur from UV exposure.
Consequences: severe sunburn, solar keratoses, ++ freckles, blistering, photosensitivity
118
Which aas are hydrophobic? How can we see this from their molecular structure?
Their side chains are composed solely of Cs and Hs.
| Glycine, proline, alanine, valine, leucine, isoleucine, methionine.
119
Why are some amino acid side chains charged at physiological pH?
It depends in their pKa. At pKa = pH, 50/50 protonated to deprotonated forms.
If pH < pKa, ie more acidic, then there are more H in solution, so aa is more likely to capture some then release more, so, it is majoritarily in its protonated form.
If pH > pKa, ie. less acidic, then there are less H in solution, ao aa is more likely to release H, thus being under deprotonated form.
120
What is the isoelectric point?
It is a pH at which the overall net charge of the PROTEIN is neutral.
121
A protein has an isoelectric point of 5. If it is placed in an electrical field at physiological pH, would it move towards + or - electrode?
it is neutral at pH of 5. So at pH of 7.4, it will release H, thus becoming negatively charged. So it is attracted by + electrode.
122
What is the difference between an oncogene and a proto-oncogene?
Proto-oncogene: is a normal gene that could become an oncogene due to mutations or increased expression.
Oncogene: have the potential to cause cancer. in tumour cells they are often mutated of highly expressed. oncogenes can induce survival and/or proliferation of altered cells that would normally be destined toapoptosis.
123
What is special about the capping of mRNA?
it is a 5' 5' link
124
What are the 2 roles of the mRNA cap?
1. prtection against degradation
| 2. Ribosomal recognition during translation
125
How many genes code for a-globin chain of haemoglobin?
4
126
How many genes code for b-globin chains in one individual?
2: one maternal, one paternal
127
How many genes code for a-globin chain of haemoglobin?
4
128
How many genes code for b-globin chains in one individual?
2: one maternal, one paternal
129
What do we mean by "sickle cell shows codominance"
This means that people can have the sickle cell trait. The disease is autosomal recessive, but the carriers though not affected will still express some sickle RBCs. This is protective against makaria.
130
What is the difference between an oncogene and a protooncogene?
An oncogene had the potential to cause cancer
| A proto-oncogene could have the potential to cause cancer if subject to mutation.
131
is a gain of function mutation more likely to cause a dominant or a recessive trait?
dominant! as a gain of something cannot be compensated, whereas a loss of soemthing can be compensated by the other chromosome having its normal function.
132
If haemoglobin subunits were dissociated what would their binding curve look like?
it wiuld be hyperbolic, there would no longer be the cooperativity effect.
133
What is aCGH.
Array comparative genome hybridisation.
it compares AMOUNTS of DNA. always comparative between normal dna and patient dna.
analysis of the whole genome.
it doesn't pick up balanced translocations because the a,ount of dna is the same.
134
Which clotting cascade factors need Vitamin K for their synthesis?
7,8,9,10
135
What is warfarin? And how does it work?
warfarin is an anticoagulant
- analogue of Vitamin K
- it blocks enzyme epoxide reductase for which Vitamin K is a co-factor
- epoxide reductase normally recycles Vitamin K after it has carboxylates clotting factors for their synthesis.
136
Which organ produces clotting factors?
the liver (also produces most other plsma proteins albumin, etc)
137
What is the intrinsic clotting pathway?
- It is set off by event inside the vessel, ie. chemicals, platelets, collagen.
- It starts with factor 12. (12->11->9->10)
- Only has minor role in activation clot formation
138
What is the extrinsic pathway of coagulation cascade?
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Caused by external trauma causing blood to escape from the vascular system. Thus exposing Tissue Factor (surface protein expressed in subendothelial cells)
Tissue factor (TF) is a transmembrane receptor for Factor VII/VIIa (FVII/VIIa). It is constitutively expressed by cells surrounding blood vessels. The endothelium physically separates this potent “activator” from its circulating ligand FVII/FVIIa and prevents inappropriate activation of the clotting cascade. Breakage of the endothelial barrier leads to exposure of extravascular TF and rapid activation of the clotting cascade. TF is also expressed in certain tissues, such as the heart and brain, and provides additional hemostatic protection to these tissues.
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139
What is the mutation that causes sickle cell disease?
A to T, changing the amino acids from Glutamate to Valine. Glutamate is negatively charged, and valine is neutral and hydrophobic (clumping of haemoglobin because of the hydrophibicity)
140
What is the end product of oogenesis? How many gametes are produced?
The end product of oogenesis is 1 ovum and 3 polar bodies.
| each are aplpid, 1n1c
141
What is the end product of spermatogenesis?
4 haploid sperm cells 1n1c.
142
When does oogenesis start?
In the foetus
143
when does spermatogenesis start?
at puberty
144
What are the 2 stages at which oogenesis is arrested, and what enables the process to resume?
The first arrest is of primary ovocytes in Prophase I.
They are arrested till ovulation, where they resume meiosis I and engage in meiosis II.
The second arrest is of secondary ovocytes in Metaphase II.
They are arrested until fertilisation which enables process to resume and finally gives rise to an ovotid (future ovum)
145
What component is found in artery walls but not in veins?
Internal elastic lamina
| External elastic lamina
146
What are the layers of an artery from the inside out?
Tunica intima:
- endothelium
- subendothelium
Internal Elastic lamina
Tunica Media
External elastic lamina
Tunica Adventitia:
- vasa vasorum
- nerves
- lympathics
