Genetics Semester 2 Flashcards
When a virus is in it’s extracelluar state what is it called?
Viron.
When a virus is in its intracellular state what is it called?
Replicative state.
What do viruses use from the host?
Metabolic and Replicative machinery.
What size can a genome be?
0.5kb-1000kb.
What are all virus genomes to small for?
Independent life.
How many proteins make up the capsid in TMV?
7.
Why is the coat of a virus being able to self assemble a good thing?
It means less genes are required.
What sort of genetic material is found in TMV?
ssRNA.
What shape is TMV?
Rod.
What do capsomers make up?
The capsid.
What is an isoheadron made up of?
20 identical triangular faces.
What symmetry does a isoheadron have?
2,3 and 5 fold symmetry.
What does not have the isoheadron structure?
Flu and phage viruses.
What are the most numerous microorganisms?
Viruses.
What are the 5 steps of a viral infection?
- Attachment
- Penetration
- Synthesis of nucleic acid.
- Maturation
- Release.
Does the virus have all the machinery needed to assemble the coat?
No. It may have some though.
What type of nucleic acids do the bacterial virus T4 phage have?
Double stranded DNA.
How many proteins does the T4 virus encode for?
Around 250.
What is the structure of the T4 genome?
Circularly permuted.
What is added to the end of the genome sequence in the T4 phage to ensure the genome is the correct size to fit the head?
Terminal repeats.
What is the time course between infection and lysis in a T4 phage?
25 minutes.
What do early proteins encode for?
Nucleases, DNA polymerase, sigma factors.
What do late proteins encode for?
T4 lysosomes and structural proteins.
What mechanisms are in place to ensure that the T4 genes are transcribed and not the hosts?
- Sigma factors to confer specificity.
- Phage promoters modify host RNAP
- Anti sigma factors.
What does the T4 pages anti sigma factor bind to?
Sigma 70 preventing host transcription.
What happens to allow the synthesis of middle proteins?
Early phage proteins modify host RNAP alpha subunits so middle promotes are recognised.
Does T4 encode it’s own RNA polymerase?
No.
What guides RNAP to middle promotor sites?
MOTA.
How are late proteins transcribed?
A new sigma factor is encoded for.
<p>What is the prophage form of the virus?</p>
<p>When the viralDNA is integrated into the host.</p>
A trigger brings about what to change the pathway from lysogenic to lytic?
Induction.
Is all the viral DNA integrated into the host DNA during the lysogenic pathway?
No. Some can remain as the plasmid.
What needs to be turned off in order to enter the lytic pathway?
The repressor to switch of viral protein synthesis.
What does a bacteriophage infect?
E.coli.
<p>What type of nucleic acid does the bacteriophage have?</p>
<p>dsDNA (linear).</p>
What is the attachment site that the bacteriophage integrates into?
Att lambda.
What enzyme is needed to allow the bacteriophage to infect ecoli?
Lambda intergrase.
What happens to the bacteriophage DNA once it has been injected?
It becomes circular.
<p>What type of replication is in the lytic pathway of bacteriophage?</p>
<p>Rolling circle replication.</p>
What happens in rolling circle replication?
A strand of the circular genome is nicked. The single stranded concatomer is then used as a template.
The cos site is cut.
How does intergrase get into the host genome?
Productions of specific late proteins.
<p>What does the lambda repressor repress (in ecoli) ?</p>
<p>Synthesis of all other lambda proteins.</p>
What does the cro repressor repress?
Expression of CIII and CI/ CI Synthesis. These commit the cell to lysis.
What is an example of a (+) strand RNA virus?
Polio, rhinovirus, hepatitis A.
These are all very small.
Capping does not occur in the poliovirus. What happens instead?
The RNA folds into stem loops to mimic the cap with VPG.
How many bases does poliovirus have?
7433.
In the polio virus where does replication occur?
The cytoplasm.
How is the host RNA synthesis inhibited with the poliovirus?
The host cap binding protein is destroyed.
What enzyme allows the synthesis of a - strand then a + strand with poliovirus?
RNA replicase. This is encoded for by the poliovirus polyprotein.
If you have ss (+) RNA what can it also act as?
A messenger.
The combination of the messenger property and the VPG cap mean it can be mistakes as host RNA.
What does destruction of the hosts cap binding protein result in?
Host RNA synthesis being switched off.
is ssRNA (-) the same as mRNA?
No. This means it is not recognised by the host.
What are examples of ssRNA (-) viruses?
Rabies, influenza, Ebola.
Do (-) ssRNA have a enveloped or capsid structure?
Enveloped.
The transcription of what is essential in (-) RNA viruses?
A virus encoded RNA replicase or polymerase.
When the rhabdovirus and the influenza virus leave the host what do they take with it?
A piece of the membrane.
How many classes of RNA are transcribed from (-) RNA viruses such as the rhabdovirus?
- This is because + strands need to be encoded so that the virus can be transcribed.
How many ssRNA molecules are in influenza?
8.
Does the influenza virus have it’s own RNA replicase?
Yes.
What is the role of RNA endonuclease in the influenza virus?
It removes the primer from host capped mRNA precursors.
What are Neurominidase and Hemagglutinin?
They are found on the surface of the influenza virus and are recognised by the hosts immune system.
Neuramindase breaks down in the respiratory tract and Heamglutin allows the virus to bind.
What activates the RNA replicase in influenza?
Uncoating.
What is added to the viral RNA in influenza?
A polyA tail. It is already capped.
What causes antigenic drift?
A fragmented genome.
<p>What is antigenic drift?</p>
<p>A change to the proteins surface on the virusbut not the active site.</p>
How does a fragmented genome cause antigenic drift?
It allows more that one infection at a time.
What does antigentic drift cause?
Antigentic shift.
What is the only DNA eukaryote virus not to replicate in the nucleus?
Pox.
<p>What can the polyomavirus: SV40 do?</p>
<p>Induce tumours.</p>
<p>What does SV40 not have?</p>
<p>Any virally encoded proteins.</p>
What is SV40 regularly used as?
a vector.
The dark gene is found in the SV40 genetic map. What does this encode?
Small and large T antigens. These are involved in binding to the origin of replication.
How are the genes arranged in the SV40 genome?
They overlap. This saves space.
How is DNA converted into RNA in the SV40 virus?
Host cellular RNA is used to make the transcript of early genes.
What happens to the RNA made by cellular RNA from the early region?
It is split into 2 capped MRNAs.
Why can’t SV40 encode it’s own RNA polymerase?
The genome is too small.
How is the late MRNA synthesised in SV40?
From the complementary strand used in early synthesis.
Is the SV40 genome bidirectional?
Yes.
Late RNA in the SV40 virus is processed normally to correspond to what?
The VP1 and VP2 coat proteins.
What happens to the MRNA encoding coat proteins VP1 and VP2 in SV40?
It leaves the nucleus to be translated and re enters to be assembled into the coat.
What do non permissive cells allow?
DNA integration and not normal viral replication. This will cause cancer.
What two viruses use reverse transcriptase?
Retrovirus (RNA) hepadnavirus.
What type of RNA strand does the retrovirus have and how many off them?
2 (+) strands.
What is the correct order for the pol gag env genes in the reterovirus?
Gag pol env.
What does the gag gene code for in the reterovirus?
Structural/ coat proteins and proteases.
What does the pol gene code for in the reterovirus?
Reverse transcriptase and intergrase.
What does the env gene encode for in the reterovirus?
Envelope proteins.
<p>Where does reverse transcriptase get its primer from?</p>
<p>It steals it from a previous host.</p>
<p>What type of molecule is the reverse transcriptase primer?</p>
<p>tRNA.</p>
What are the 8 steps of reverse transcriptase?
Entrance, uncoating, reverse transcription, traveling to nucleus and integrated into host DNA, transcription, encapsidation, budding, release.
What does encapsidation consist of?
The viral RNA has two paths, it can either be re used as a messenger or packed by viral proteins to form genomic RNA in a capsid. This second process is encapsidation.
What does activation of promoters in the LTR repeat regions lead to?
Capped and polyadenylated mRNA.
What is the gene organisation in the hepadnavirus virus?
The genes overlap.
What type of nucleic acid is in the hepadnavirus?
Partial dsDNA.
How does the hepadnavirus replicate?
Through an RNA intermediate.
Uses the hosts machinery for DNA to RNA then it’s own reverse transcriptase for RNA to DNA.
What happens to the virus particles in a persistent infection?
They are slowly released.
What checkpoint does the anaphase promoting complex as a ubiquitin ligase on?
Metaphase checkpoint.
If the kinetochores are not attached to the microtubules what can this inhibit?
The anaphase promoting complex.
What must the activated anaphase promoting complex include?
CDC20 protein.
What can the cdc20 protein in the APC bind to?
Mad/bun protein complex.
When will the mad/bub protein complex form?
When kinetochores are not bound to the the microtubules.
When the anaphase protein complex is bound to the mad/bub complex is it active or inactive?
Inactive. Securin is not broken down.
What do cell cycle arrest and apoptosis both depend on?
C53 protein.
What does the presence of transcription factor P53 allow?
The transcription of p21.
What does p21 inhibit?
CDK cyclin activity.
What happens when P53 is phosphorylated?
It is active.
What type of molecule is mdm2? What is it’s role?
It is a ubiquitin ligase which degrades P53.
What prevents the degradation of P53 by mdm2?
The fact that it is phosphorylated.
Why do all organism have to go through a bottleneck?
As at one point they are only one cell.
What does the Antemepeadia mutation in drosophila result in?
Legs where the antenna should be.
What happens when the ‘dorsel lip of the blastopore’ is transplanted into a different place?
A whole new embryo forms.
What did Hans Spearman do?
Found that an organiser induced formation of another embryo.
What is a tetragen?
An agent which causes birth defects eh thalidomide.
What is phocomelia?
Limb shortening.
What type of organism is C. elegans?
A nemotode worm.
How many adult somatic cells are in C. elegans?
954 (it is very small) .
Who got a Nobel prize for their work on C. elegans?
Brenner, Sulston and Howitz.
What organism was early work on apoptosis done on?
C. elegans.
Does Drosphila melangastor have mitotic cell division?
No. There is no G phase so the cycle is greatly accelerated.
How long is D. melangastor a embryonic development?
A day.
What does D. melangastors embryo run from?
Anterior to posterior.
What cells in DM form first and give rise to the germline?
Posterior cells.
Once the first few cells in DM have gained a membrane what sort of structure is formed?
A hollow one.
In DM developed cells move from P to A to P. What is also formed?
Layers of cells called blastomyces.
What is formed at the Anterior end in DM?
Head.
What is the first movement that DM experiences?
The trachea filling with air.
What type of organism is Xenopus laevis?
An African clawed toad.
What is Arabidopis thaliana?
A model organism plant.
What happens in mosaic development?
Organisation is maintained.
What happens in regulative development?
There is no information on organisation.
Laser ablation has an effect on which development form?
Mosaic.
Transplantation has an effect on which development form?
Mosaic.
What sort of development is present in DM and the nemotoad?
Mosaic.
What sort of development is used by humans and sea urchins?
Regulative.
Where does the frog develop?
On top of the yolk.
What are the 5 steps in the frog life cycle?
- Fertilisation
- Cleavage/ Blasulation
- Gastulation
- Organogenesis
- Cell differentiation.
What is the purpose of cleavage/ Blasulation?
Produces a large number of cells.
What is the purpose of gastulation?
Allows rearrangement of cells.
What develops in the ectoderm?
Nervous system and skin.
What cells development in the mesoderm?
Heart, muscles, skeleton, kidney.
What develops in the endoderm?
Lungs, liver, gut.
What do morphogens do?
Create asymmetry and patterns.
When was DMs genome sequenced?
1997.
How long is the life cycle of DM?
12 days. It is only larva for 24 hours allowing quick observations.
What does DM start of as?
A maggot that feeds ok yeast.
What does an oocyte have at fertilisation?
Polarity.
<p>What is the purpose of nuse cells?</p>
<p>To support the oocyte.</p>
Proteins and mRNA are held in the Nurse cells in what state up until fertilisation?
Untranslational.
After the fertilisation only the nuclei divide for the first 9 times. What does this result in?
A syncytium.
Where do nuclei migrate to after fertilisation to form a blastoderm?
The eggs surface.
What does the morphogenetic gradients of bicos and nanos genes help the cell know?
Where it is in the embryo.
What recognises gene products to allow the concentrations to be seen on morphogenetic gradients with a densitrometric scanner?
Antibodies.
What are early segments called?
Parasegments.
What does the modified ring, also know as the halotere allow DM to do?
Balance.
How many segments are in the abdomen?
8.
Where are maternal effect genes active?
Maternal cells.
What do maternal effect genes control?
mRNA tethering to A and P.
Where are zygotic genes active?
In the mother.
What are the two types of zygotic genes?
Segmentation and homeotic selector genes.
What do segmentation genes do?
Divide the embryo up via division of Parasegments.
What do geographical selector genes control?
Control other banks of genes to allow development of specialised structures including legs.
What does the posterior end of the cell contain?
Posterior pole plasm.
Where do the nuclei move to give rise to the germline?
The posterior pole plasm.
Wha determines fertility in DM?
The genotype of the mother.
What are the three classes of segmentation genes?
Gap, pair rule and segment polarity genes.
What is ‘hunchback’ and example of?
A gap gene.
What pattern is the hunchback gene expressed in?
Broad bands in the central. Other gap genes express similar bands in slightly different positions.
What regulates pair rule gene expression?
Combination of gap gene expression.
What are ‘eve’ and ‘runt’ examples of?
Pair rule genes.
What are the bands like expressed by pair rule genes?
Narrower bands. Expressed in alternative parasegments.
What controls the expression of segmentation genes?
The combination of pair rule genes expressed.
What is ‘fushi tarazu’ an example of?
Segmentation gene.
How many parasegments do the segment polarity genes organise?
14.
When are homeotic selector genes activated?
Once segmentation has been established by the segmentation genes.
What do homeotic selector genes do?
Specify the identity of each segment.
How are related genes in DM organised in it’s genome?
They are clustered on one chromosome.
What does the order of genes in DM correspond to in DM?
Spatial organisation.
What can homeotic selector genes signal?
Changes in gene expression.
What are the two clusters of genes called in DM?
The Antennepeadia complex and the Bithoroax complex.
Are mammals segmented during embryonic development?
No.
How big is the homeobox DNA binding domain?
180bp.
What does an abnormality in the HOXD13 gene cause?
The wrong number of toes.
Nb there is also a PAX6 gene that also causes inherited development.
What does a mutation in the hox gene cause?
A lip mutation.
What do segmentation genes in early mammalian development control formation of?
Bone, blood and gentiles.
What does a mutation in the runt gene cause?
Skeletal defects.
What is the definition of epigenetics?
Heritable changes in gene expression associates with unchanged DNA sequence.
What bases pair is methylated in mammals?
CG.
What position does methylation occur?
5 position of cytosine ring.
What enzyme adds the methyl group to the CG base pair?
Methyl transferase.
Are genes expressed when they are methylated?
Generally not
What type of regulation is methylation?
Long term.
How many histones make up the core that DNA can wind round?
8.
How many times does DNA wind around the histone?
Twice.
What happens to hemi methylated DNA?
The other strand is then methylated.
What structure is the histone when in when transcription is occurring?
Open.
When open are nucleosomes acetates or deacylated?
Acylated.
What type of modification is more rigid, methylation or acetylation?
Methylation.
What happens to the chromosomes when they are between acylation states?
The chromatin can be remodelled.
When do nucleosomes need to be briefly disassembled?
When the replication fork reaches the nucleosome.
When the nucleosome is reassembled is it made of new histones, old histones or both?
Both.
What is RNA induced transcriptional silencing?
When the RNA transcript regulates gene activity. It can also influence to structure.
When the RNA transcript regulates gene activity what does it interact with?
The chromatin.
Is X activation rare in mammals?
No it happens in almost all mammals.
In a human roughly how many genes are found on the X chromosome?
1000.
There are regions that are homologous on the sex chromosomes to allow pairing. How big are these regions?
They are small.
What epigenetic mechanisms allow for X inactivation in mammals?
Methylation, acetylation and RNA induced transcriptional silencing.
In mammals does it matter what X is inactivated?
No. It is random.
What type of chromatin is found in the inactivated X chromosome?
heterochomatin.
What can the inactive X chromosome be visualised as?
A Barr body.
Random inactivation of X causes females to be mosaic. What is an example of this?
The calico cat with black and orange patches.
What happens to the mothers gene in maternal imprinting?
The mothers gene becomes inactive.
What happens in parental imprinting?
The X chromosome from the father is inactive.
What type of imprinting is Angleman syndrome?
Paternal. UBE3A is turned off.
What are the symptoms of Angleman syndrome?
Mental impairment.
What type of imprinting occurs in Prader-Willi syndrome?
Maternal, on the SNRPN gene and the NDN gene.
What are the symptoms of Prader-Willi syndrome?
Chronic hunger.
Is imprinting reset in the germline?
Yes.
What is parthenogenesis?
A type of asexual production when an offspring can develop from an unfertilised egg. This does not happen in mammals.
When is there not a conflict of interest in parents?
When there is absolute monogamy.
IGF2 is expressed in the foetus. What type of imprinting does it show?
Maternal.
What type of imprinting does IFG2R allow?
Paternal.
What type of potency is present in the zygote?
Totipotency.
What type of potency is present in the blastocyte?
Pluripotent.
What type of potency is present in an adult cell?
Multipotent.
What does pluripotency mean?
All embryonic cell type and adult cell type are present but you can not grow a whole organism from it.
Can stem cells self renew?
Yes.
What are progenifer cells?
Cells partly committed to differentiation so only have limited self renewal. Derived from stem cells.
What is the structure of a blastocyst?
A hollow ball structure of approximately 120 cells.
What are the cells called in the blastocyst that give rise to extra embryonic structures?
Trophoblasts.
Where is the inner cell mass present in a blastocyst?
One side.
What will the inner cell mass ultimately become?
An embryo.
What are embryonic stem cells derived from?
The inner cell mass.
Why can embryonic stem cells be used in therapeutic cloning?
If it is a persons own ESC they will not reject them.
Why do the ESC need to be reprogrammed before being use in therapeutic cloning?
They can develop into cancer.
What are IPSC’s
Induced pluripotent stem cells.
What can induced pluripotent stem cells possibly be used to treat?
Amyotrophic lateral sclerosis.
Do induced pluripotent stem cells closely reassemble normal stem cells?
It is not known.
Do single gene genetic disorders follow Mendelian inheritance?
Yes.
What sort of penetrance do single gene disorders have?
High.
Are complex disorders more common than simple disorders?
Yes.
Are there reliable predictive tests for simple or complex disorders?
Simple.
Are simple or complex disorders more greatly influenced by the environment?
Complex.
What percentage of contractions will terminate due to chromosomal mutation?
50%.
5% of births require hospitalisation. Of this 5% what percentage have a Mendelian disorder?
2-3%
5% of births require hospitalisation. Of this 5% what percentage have a chromosomal disorder?
2%
5% of births require hospitalisation. Of this 5% what percentage have a multifactorial disorder?
0.5%
How many base pairs are there in the human genome?
3 x 10^9
What do genetic maps only work on?
Polymorphic areas.
What do clone maps use?
A series of overlapping clones.
What publicly funded lab in the UK is known for it’s work on mapping genomes?
Welcome Trust.
What private company tried to map the genome first?
Celera Genomics.
When was the human genome first roughly sequenced?
2000.
When was the human genome first aciratkwy sequenced?
2003-2004.
How many potentially harmful mutations do we all have?
160-190.
What often causes rare genetic disorders?
Cousin marriages.
How is the UK’s 100000 genome project aiming to help cure cancer?
It is aiming to find known molecule causes of cancer to allow personalised treatment, eg herceptin for Her 2 ve+ breast cancer.
Is there genetic variation in tumours?
Yes. This can explain why there is often a relapse after chemotherapy.
Where is it thought that the first human species originated 50000years ago?
Africa.
Where are humans of Denisovan admixture found?
Australasia.
Is any Denisovan mixture found in Asia?
No.
Where is Neanderthal admixture found?
Europe.
Does modern human sequencing show interbreeding between original groups of humans?
Yes.
What was found in the Denisova cave in Siberia?
A finger bone with 1/3 of an hominids sequence.
Where is it thought that there could be a ghost population of humans?
The Philippians.
Where is Tibetan altitude tolerance thought to have come from?
The Deniosovans. It is the EPAS1 locus that controls haemoglobin synthesis.
What percentage of human DNA encodes for proteins?
1.1%
How many genes does a human have? Is this a lot compared to other organisms?
20,500 genes. No considering C.elegans has 20,000 genes.
What percentage of DNA is conserved?
8%
What percentage of DNA is replicative?
50%. Some of this has a structural role such as with telomeres and centromeres.
What percentage of DNA is transcribed?
80%. It is unknown why this number is so high.
What is the whole ecoli genome the same size as?
A human gene.
What percentage of most genes actually encodes for a protein?
2-3%.
How much DNA is in each cell?
3m.
Can mutations in non coding regions effect phenotype?
Yes but less dramatically.
Does changing how the DNA expressed change the phenotype?
Yes.
What does ENCODE stand for?
Encyclopaedia of DNA Elements.
Are autosomal dominant inheritance diseases selected against?
Yes.
Familial hypercholesterolenemia is a autosomal dominant disease. How many people have it?
1/500.
Huntings is an example of an autosomal dominant disease. What proportion of the population suffer from it?
1/6500.
Duchenne MD and Fragile X symptom are examples of what?
Diseases caused by sex linked inheritance.
What does OMIM stand for?
Online Mendelian Inheritance in Man.
For how many Mendelian disorders is the molecular base sequence known?
Roughly 4000.
For how many Mendelian disorders is the gene known but not the defect?
Roughly 1500.
For how many Mendelian disorders is the gene not known?
Roughly 1500.
What can molecular polymorphism be used for?
Genetic markers.
What race is most susceptible to cystic fibrosis?
Caucasians originating from Northern Europe.
Tays- Sachs disease causes nerve degeneration. What race is most susceptible?
Ashkenazi Jews.
How is phenylketonuria, a disease where the sufferer is allergic to phenylanaline is being controlled by what method?
Children are now being screened for the disorder.
Sickle cell and Thalassemias are more abundant in populations prone to get malaria, by what percentage?
1-2%.
What is the mismatch repair system used in?
DNA repair when an imperfect duplex is recognised.
In missense mutations a change in which amino acids in the codon are important?
1 and 2. 3 is often described as a ‘ghost’ amino acid due to the code being degenerate.
What is a nonsense mutation?
A change in a codon that does not code for an amino acid.
What can an insertion or deletion mutation cause?
A frame shift.
What can cause a repeat expansion mutation?
‘Slipage’ in replication or crossing over errors.
Can there be expansion and contraction of repeats between generations?
Yes.
What causes the formation of thymidine dimers?
UV light.
When is a mutation not heredity?
When it is not in the germline.
What causes autosomal recessive genes to become more abundant in certain populations?
The founders effect.
Some genetic alleles work in an _______ context to create a phenotype.
Environmental. For example with lung cancer and smoking.
What can have a major impact on histones and their post translational modification?
Diet.
What do oncee genes do?
Regulate cell cycle and proliferation. Can also be tumour suppressor genes.
What 3 types of chromosomal change need 3 damages sites?
Insertions, deletions and duplications.
What 2 types of chromosomal change need 2 damages sites?
Reciprocal translocations and inversions.
Are chromosomal changes with 2 or 3 damage sites more common?
2.
When chromosomes are structurally changed it always causes a genetic imbalance. True or False?
False. It only causes a genetic imbalance when there is a duplication.
Does a duplication in a chromosome always cause more genes?
Not necessarily, just more DNA.
Why can insertions and reciprocal translations cause sufficient change in gene expression?
Because a promotor may have been inserted where it shouldn’t be (or removed from where it should) however this is rare.
What is the synaptic complex?
3 parallel protein tracks between fully paired chromosomes. At the stage you can not distinguish between chromosomes and chromatids.
What are sister chromatids held together by?
Cohesion.
What are non sister chromatids help together by?
Crossovers.
What forms to allow pairing after an inversion?
An inversion loop.
When does an inversion loop cause a defect?
When there is crossing over in the inversion loop.
What does a acentric fragment not contain and what damage does this cause?
It does not contain a centromere so the kinetochore can not bind and separation can not occur in anaphase.
Half of gametes can be lost.
What type of inversion causes a dicentric bridge?
A paracentric inversion.
When a chromosome does not contain a centromere (meaning it can get lost) what is it called?
A legard.
What happens due to pericentric inversions?
Duplications and deletions.
What chromosomes have different P bands as they code for rDNA?
13,14,15,21,22.
Why does it not matter if you loose the p bands on chromosomes 13,14,15,21,22 ?
Because they contain rDNA which there are lots of copies of meaning it does not matter if some are lost.
What fuses together to form a trivalent?
A loose P and a loose Q arm.
What three things can cause birth defects?
- Environmental factors.
- Mutation at a gene level.
- Chromosomal abnormalities.
Are X chromosomes completely inactive in the process of X inactivation?
No. Some genes are still active.
What type of retardation is commonly derived from a genetic abnormality?
Mental.
What percentage it stillborns and neonatal deaths are caused by chromosome aberrations?
At least 40%
How many live births have a karyotypic abnormalities, even if they are not clinically significant?
1/160.
What percentage of human conceptions lead to spontaneous abortions or miscarriages?
20-40%
What is the definition of nondisjunction?
Nondisjunction is the failure of 2 homologous chromosomes or sister chromatids to separate/ disjoin during mitosis or meiosis.
During mitosis if one pair of sister chromatids do not separate what types of daughter cells do you get?
1 monosomic
1 trisomic
If there is a failure of separase in meiosis meaning that a homologous pair can not separate in meiosis what daughter cells do you get?
2 disomic daughter cells and 2 nullisomic daughter cells (all haploid).
If there is only a loss of sister chromatid cohesion in arms during meiosis 2 there will be nordisjuction. What daughter cells do these result in?
One disomic cell, one nullisomic daughter cell and one haploid cell. All haploid.
What is trisomy 18 also known as?
Edwards syndrome.
What is trisomy 21 also known as?
Down syndrome.
Trisomy 22 will never have live born. True or false?
False. Trisomy 16 never causes live borns.
If someone exhibits multiple dystrophic features of someone with a common genetic disorder do they definitely have a common genetic disorder?
No. There is a possibility that the multiple dysmorphic features could be caused by environmental factors, for example foetal alcohol syndrome.
Name our reasons why genes should be mapped and cloned?
Allows genetic testing, parental diagnostics, disease diagnostics, knowledge of proteins and their function, molecular pathology and better treatment possibilities.
What must the marker gene not do?
Effect the phenotype.
How can three point crosses be used in mapping?
They can be used to look for any linkage between the gene causing the disease and the mapping marker.
How should mapping markers be spread through the genome?
Evenly.
When does someone with Huntington’s disease usually develop it?
When they are older - it is a late onset disease.
Can Huntington’s disease cause personality changes or is it just a movement disorder?
It can causes personality changes. The patient is often psychotic.
Huntington’s disease causes loss of cells from the ________ __________. This causes general brain shortage and neuronal death.
Corpus striatum.
What genetic change causes Huntington’s disease?
Trionucleotide repeat expansion of the ORF.
What sequence is repeated in the ORF of someone with Huntington’s disease?
CAG.
If CAG is repeated >40 times what type of Huntington’s will the patient have?
Adult onset.
If CAG is repeated 70> times what sort of Huntington’s will the patient have?
Early onset.
The repeats found in someone with Huntington’s increase through generations. What type of disease is Huntington’s hence described as ?
Anticipation disease.
What does CAG encode ?
Glutamine.
In Huntington’s disease proteins become insoluble meaning it forms inclusion bodies. What causes this to happen?
Polyglutamine tract.
What is the carrier frequency of CF?
7/22.
What does CF cause the mucus to become?
Thick and Dehydrated.
What does CF cause?
Repeated bacterial infections, chronic inflammation and overproduction of elastases.
Is it only the lungs affected by CF?
No.
What is the main diagnostic of CF?
Salty sweat.
70% of mutations in CF are caused by what gene?
F508.
What age of onset does DMD have?
Between 3 and 5 years.
What sort of mutation normally causes DMD
Newly arised deletions.
What protein is effected in Huntington’s disease?
The Huntingdon protein.
What happens to the Huntington protein in Huntigdon’s disease and why does this cause damage?
The protein is cleaved by proteases which can migrate into the nucleus.
What does CFTR do?
Pumps chloride out of the cell. this causes water to follow and the mucus to become hydrated. Sodium ions are transported into the cell.
What can not diffuse out of the cell in someone with CF?
Chloride ions. this stops osmosis of water out of the cell. Sodium ions can still enter the cell.
What happens to the muscle of someone with DMD?
The muscle stops being repaired and it starts to break down.
Even if a trait shows high heritability someone with the faulty gene may not show the faulty phenotype. Why is this?
Because environmental factors also play a key role, for example with smoking and lung cancer.
What does heritability measure?
The proportion of absorbed variance that is due to genetic variation. It does not measure the extent in which a disorder is genetic.
What is variance measure by?
Concordance.
What is concordance?
The frequency that the second twin also exhibits a trait or suffers from a disorder where the trait is also shown in the first twin.
What does H2 equal?
2 x (concordance of MZT - concordance of DZT)
When will concordance distinguish between environmental and genetic factors?
When the twins have been reared apart.
What do association studies show?
that the allele frequency is higher in affected individuals than in the controlled.
What is a SNiP
Single nucleotide polymorphism.
How many common SNiPs are in the human genome?
Around 15 million meaning they are common ( minor allele frequency >5%).
Although SNiPs do not have a radical effect on the phenotype, what can they contribute too?
Complex diseases.
What is the genome compromised of?
Haplotype blocks.
How can you recognise haplotype boxes?
Tag SNPs/ In a block there is only a limited amount of combinations. There is linkage disequilibrium.
What protein increases the risk of Alzheimer’s?
Apolipoprotein E. It is a common allele which is present in 16% of the gene pool.
Apolipoprotein E increases the risk of Alzheimer’s by a factor of three. What factor is the risk increased by when the person has two copies of the allele?
8.
Residue 57 (asparate) at the HLA locus DQB1 increases the risk of what?
Type one diabetes.
Residue 57 (asparate) at the HLA locus DQB1 increases the risk of type one diabetes by a factor of 6 for a person with one allele. What factor is the risk increased by when a person has two alleles?
18.
What did the Genome Wide Association Study (GWAS) identify?
A panel of around 1 million SNiPs that spans the genome.
Where are SNiPs generally not found?
In obvious genes. They generally only identify a section of the genome that is at risk.
In the GWAS cases of controls and affected individuals where used. How many individuals where in this study?
10,000.
Due to the fact each SNiP represented a separate test the statistical o value would be to high at 10^-8 which could give false negatives. How is this avoided?
The level of significance was increased, but not to a point where it also gave rise to false positives.
The Genome Wide Association study only explained a maximum variance of what?
20%. This is potentially because many alleles have a tiny effect.
The environment has the same effect on each gene. True or False?
False. The significance of the environment has on how the gene is expressed depends on the gene.
Appetite is not controlled by genetics. True or False?
False.
Klinefelter syndrome results in there being three sex chromosomes: XXY. Can the extra X chromosome come from either parent?
Yes.
In an XYY male one of the X chromosomes has to come from the mother meaning the male contributes YY. Can you tell if this was an error in first segregation or the second?
Yes, it has to be second. This is because males can have XY. If it was in the female as they can only have XX then it can be either.
Is the female or male checkpoint system more robust?
Male.
How many genes are inactivated in someone with triple X syndrome?
2.
Where does the extra X normally always come from in someone with triple X syndrome?
The mother.
If a female has variation in her menstrual cycle, fertility problems, is above average height, sometimes described as being antisocial and has a lower IQ than her family what syndrome may she be suffering from?
XXX.
What has it been wrongly suggested about XXY males?
That they have antisocial behaviour.
What is turner syndrome?
XO.
What percentage of XO foetuses are lost naturally and what does this tell us about X inactivation?
97%. This tell us that the few genes not turned of by X inactivation are critical for survival.
How can you end up with an XX XO mosaic, which is apparent in 50% of Turner cases?
An error in mitosis
Cystic swelling in the neck, generalized subcutaneous oedema, infertility due to ovaries failing to develop, immature external genitalia and narrowing of the aorta are all symptoms of what syndrome?
Turners syndrome.
How was it discovered that the faulty allele came from the father in Turners syndrome?
Girls with turners syndrome were being born without colour blindness when their dads were colour blind.
Is the IQ of someone with Turners syndrome usually lower?
No, but they are less skilled.
What percentage of babies with trisomy 21 are lost by spontaneous abortion or early post natal death associated with congenital heart disease?
75%.
In 95% of Down syndrome the extra chromosome is gained from the _____ due to nordisjunction.
Mother.
What does the unbalanced Robertsonian translocation iso(21q) cause?
Down syndrome.
How is Robertsonian translocation iso(21q) caused?
The q arm of chromosome 15 and 21 conjoin. It is then possible for the whole of 21 and the q region from 21 to go into the same cell.
What is the Down syndrome critical region?
21q21.2 to q22.3.
Is fragile X syndrome more severe in males or females?
Males.
How many males suffer with fragile X?
1/2000.
How many people are carries of fragile X syndrome?
1/400.
Fragile X syndrome is caused by what chromosome?
FRAX.
Mental retardation is common in both genders who have fragile X syndrome. True or false?
False. It is common in males. Emotional and behavioural problems are common in both genders of people with fragile X syndrome.
Location of the fragile site in FRAXcan vary but all locations give rise to the same phenotype. True or false?
False. They give rise to different genotypes.
All locations of the fragile X site are equally likely. True or false?
False. FRAXA, E and F are rare. FRAXB, C and D are common. These are all different types of the disorder due to the difference in location of the fragile site.
What is almost always the underlying cause of FRAX?
Trinucleotide repeat expansion of CCG in the FMR gene.
For FRAXA what is the normal amount of expansion of CCG in the FMR gene?
5-44.
How many expansions of CCG do you need to be in the gray zone with FRAX1?
45-54.
How many expansions of CCG do you need to be in the premature zone with FRAX1?
55-200.
How many expansions of CCG do you need to have to have the full mutation with FRAX1?
> 200.
The FMR gene is expressed throughout the foetus. Where is it expressed in adults?
Neurones and testes.
Fragile X is caused due to repeats of CCG in the FMR gene. Do these repeats cause the gene not to be expressed?
No, they just causes more methylation to occur. When this occurs to much too much of the gene is inactivated and a fragile site is created.
What are all the following reasons for?
- Used to discover plasmids and phages.
- Used in cloning and sequencing.
- Needed to purify proteins.
- Allows site directed mutagenesis.
- Allows gene testing.
- Used in synthetic biology.
Why bacterial genetics are important.
What three things did Julian Huxley state incorrectly in the 1940s?
- Bacteria have no genes they are just soma/germ plasm.
- Bacteria do not have sex.
- Bacterial genetics are not significant to humans.
What is the first bacteria of choice when looking at genetics?
E.coli.
When a E.coli cell is lysed and looked at under an electron microscope, how many times longer is the DNA than the cell?
1500.
How many bases in E.coli are replicated in 20 minutes?
4.6 million.
In the human genomen there is 95% unused space, excluding exons. Is this the same for the E.coli genome?
No, there is very little unused space.
Does the E.coli genome contain Pseudogenes like the human genome ? (These are ancient gene duplicates that have now been decayed.)
No.
Strains of the same species have big differences in gene distribution. True or false?
True.
One gene is known as what type of message?
Monocistromic.
Three genes make what type of message?
Polycistronic.
How is genetic material organised in a bacteria cell?
In a nucleoid.
How many domain loops does a nucleoid contain?
30-100.
Is double helix is helical in bacteria. What term is used to describe this?
Supercoiled.
If a supercoil is nicked with a endonuclease what happens?
The supercoil relaxes and loops out.
How is supercoiling achieved?
Through a double branded break in circular DNA. Another part of the circle is then passed through this cut and the break is resealed.
When a replication bubble forms do the strands progress in the same or opposite directions?
Opposite.
How many arrest sites are present in the E.coli terminator site?
8.
The clockwise E.coli fork is trapped by what arrest sites?
ter B,C,F,G,J.
The counterclockwise E.coli fork is trapped by what arrest sites?
ter A,D,E,H,I.
DNA replication in bacteria results in a catenane of linked rings. What two methods can resolve this?
- Topisomerase IV
2. Enzymes XerC and XerD.
How do enzymes XerC and XerD unlike the rings after DNA replication in E.coli?
They recognise different sites on the molecules and catalyse the cutting and rejoining steps through the formation of a holiday junction.
Once the two circular pieces of DNA have been separated after DNA replication in E.coli, what can happen?
They can segregate to opposite poles and cell division can occur.
How can spontaneous generation through binary fission be seen in Streptomyces?
Colony colour is different.
What is special about the K12 strain of E.coli?
It is now completely non pathogenic.
There are 4288 genes in the K12 genome. Is this the same for pathogenic strains?
No, their genome is slightly bigger.
How many genes are present in the trp operon?
5.
Does the his or trp operon have more genes?
His.
Do the his and trp genome work in he same directions?
No. The his works clockwise and the trp works counter clockwise.
Pathogenic E.colin strains and the K12 strains both have plasmids. True or false?
False, K12 does not normally have plasmids.
What is Not1?
A restriction site in K12 E.coli which cuts the genome infrequently.
What is pBR322?
A common plasmid cloning vector.
What is ‘ori’ and where is it found?
It is the origin of replication in the pBR322 plasmid.
What are tet and amp?
Antibiotic resistant genes.
pBR322 was made in the lab. How many restriction sites does it have?
6.
What are pst1, Hind11, Bamh1?
Common restriction sites which originally originated from bacteria.
In the rolling circle model of replication in plasmids replication only moves one way. True or false?
True.
What is the role of RepAate in the plasmid rolling circle of replication model?
It nicks the + strand at the origin.
Plasmids can encode resistance to toxic metals. True or false?
True. They can also metabolically degrade materials such as herbicides.
Is DNA polymerase used in the rolling circle model of replication in plasmids?
Yes.
Can plasmids make virulence factors?
Yes.
What is R100?
A small resistance plasmid that is 94.3 kb in size.
What does ‘Tra’, found in R100 contain?
Transfer genes which allow the spread of antibiotic resistance.
Cat, Str and Sul are all examples of what?
Antibiotic resistance genes.
Is an orange colony of Halobacterium mutant?
Yes. They are normally colourless but the orange colonies lack gas vesicles so their colour is not obscured.
Do mutations normally effect more than one gene?
No. They normally only effect one gene or a set of nucleotides in a gene.
When you are naming genotypes do you use italics?
Yes.
Are all letters lowercase when you are naming genotypes?
No, the 4th letter is a capital. The name of a gene is always three or four letters long.
What does this represent?
cydA1, cydA2, cydA3.
Multiple alleles of the same gene.
D you use italics when describing a phenotype?
No.
What do the + and - mean in a phenotype?
Normal/ not normal.
Could you tell what allele the mutation was in in the following phenotype?
Cyd-.
No, it could be any of the Cyd alleles.
When naming proteins are italics or subscript used?
No.
Are selecting and screening mutants the same thing?
No.
You first detect a mutant with ______ and then you _____ for a precise mutation.
Selection, screen.
What are nutritional mutants also known as?
Auxotrophic mutants.
Can you get cold sensitive mutants as well as temperature sensitive mutants?
Yes.
What will chemicals reacting with DNA often cause?
Cross linking.
Does DNA have to be degraded to allow transformation?
No, but it can be.
In conjunction are the donor and recipient the same?
No.
What does transduction require?
A bacterial virus.
In transformation how does the DNA bind to the recipient cell?
By binding to multiple proteins in the recipients envelope.
Only one DNA strand enters the cell in transformation. What happens to the other strand?
It gets degraded.
In transformation what does the internalized strand bind too?
Compliance specific single stranded DNA binding proteins.
In transformation do plasmids need to be integrated?
No.
Is transduction strain specific?
Yes, it is also strain specific.
How can phases be propogated?
They can be lysed on a bacterial plate.
What bacteriophage, used in labs, can be detected by clear spots?
T2.
What did Laderburg discover in the 1950’s?
Conjuction.
What did the U-tube experiment show?
That conjunction, unlike transformation needed the recipient bacteria cell to make contact with the donor cell.
How could the U tube experiment let DNA through the filter?
By a light suction.
What type of plasmid do bacteria taking part in conjuction need?
The F plasmid.
What does tra encode?
Transforming genes.
What are insertion sequences?
Segments of bacterial DNA that can move from a region on a chromosome and recombine with different regions on the same chromosome or on a different chromosome.
What is OriT?
The origin of conjunction.
What does a F- cell not contain?
The plasmid.
What is the pillus made up off?
Large number of identical subunits.
What happens to allow the bacterial cells to move closer together in conjuction?
The pillus shreds subunits.
The pillus is thick. true or false?
False it is very thin.
What nicks the F+ plasmid?
An endonucelase.
Why does the single strand of DNA pass through a specific hole in conjuction?
So DNAP can replicate it.
What are all transfer functions enoded by?
Tra.
Does conjuction allow genetic variation to be introduced?
No.
What are hfr strains very good at?
Donating genes and moving host chromosomes,
What is a bacterium called when the F+ plasmid has been intergrated?
Hfr.
What state is the F+ plasmid?
free.
Double cross overs in which region allow the incorporation of chromosomes?
IS3.
Once a plasmid has been incorporated into the chromosomal genes hat can it no longer do?
Control its own replication.
What type of mechanism allows the transfered DNA strand to be replaced in conjunction?
The rolling circle mechanism.
Why can a plasmid still form a pillus when it has been integrated into the chromosome?
It still contains the tra region.
Does the Hfr strain transfer the F plasmid as efficiently as the F+ would have done?
Yes.
What genes are more likely to be transferred in conjuction?
Genes closer to the insertion points.
During Hfr transfer why does the new cell not become HFR?
As the new cell only contains part of the F plasmid.
How can different Hfr stains be formed?
Genes can be transferred from a different starting point and in a different direction. This meant that the arrangement and orientation of genes could be found almost perfectly before sequencing.
How long does it take for an F plasmid to transfer?
5 minutes.
Does it take a longer or shorter amount of time to transfer a chromosome compared to an F plasmid?
Much longer.
What technique can be used to break the bacterial pair up to allow mating to be disrupted at certain times?
Sonication.
All bacteria are naturally comptenant to be transformed. true or false?
False. Some need chemical treatment or electroporation.
Is transformation or transduction must widely used in labs?
transformation. Transdu tion is the senc most common method and is used to transfer small pieces od DNA.
What method is rarely used in labs in regards to genetic transfer?
Conjuction.
