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Flashcards in Genetic Variation Deck (51)
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In which direction does RNA polymerase move?


And therefore in which direction is mRNA made?

3' --> 5'


mRNA made from 5' --> 3'


What are the stages of the cell growth cycle?

G1 --> Cell prepares for cell growth


S-Phase --> DNA replicated/synthesised


G2 --> Cell prepares for division


M-Phase --> Mitosis, spindle formation and cell division


How is Cortisol secreted in the body?

Stimuli cause Corticotrophin Releasing Hormone (CRH) from the hypothalamus

This stimulates the pituitary to release AdrenoCorticoTrophic Hormone (ACTH) --> This causes the adrenals to secrete cortisol


Why can chemotherapy cause damage to our own cells, but not always the tumour cells?

Because our own cells have p53 (pro-apoptopic) and so the chemo will damage our cells enough to induce apoptosis


However the mutated tumour cells will probably not have any p53, so apoptosis will not be induced!!


Explain X-linked recessive Alleles?

The allele is on te X chromosome, so is more prevelent in females (more likely to be carriers as they have to X chromosomes)

Males only need 1 copy of the allele to be a suffer (as they only have one X-chromosome)


Explain the anti-inflammatory effects of glucocorticoids

Inhibits not the innate and adaptive immune systems


Decrease the production of inflammatory mediators (ROS, leukotrienes, complement, histamine and prostanoids)


Inhibit Th cells activation --> As well as IL-2 and clonal expansion


Decrease vasodialtion --> Preventing wbc to get to the site of infection


What are the 4 normal control mechanisms of the body to prevent loss of function from mutations?

Hetrozygosity --> 2 versions of the same gene, as there's less chance that both will get mutated


Apoptosis --> Regulated cell death to prevent the transmission of mutated genes


Cell Cycle Control --> Checkpoints during cell division ensures thats no damaged cells become fully grown (but killed by apoptosis)


Regulation of Gene Transcription --> There is a requirement for certain activation signals for gene transcription


Describe the characteristics of Adult (Somatic) Stem Cells

They can proliferate....but not indefinitely


Multipotent/unipotent cells


Located in stem cell niches


Replace worn out/dead cells --> so important for homeostasis


What is the difference between Homodimers and Heterodimers?

Homodimers --> Cytoplasmic and nuclear loacalisation

Each subunit binds one repeat as an inverted dimer, and as a palindrome


Heterodimer --> Activated by ligands binding in the nucleus

RXR forms a dimer with either...

Vitamin D receptor (VDR) --> 3 base pair spacing

Retionic Acid receptor (RAR) --> 4bp

Tridothyronine receptor (T3R) --> 5bp


Bind direct repeat half sites




What will a mutation in the gene IL36RN do?

Cause pustular psoriasis


IL36RN usually helps regulate inflammation by suppressing cytokines like IL-1


Explain two reasons for Atopic Eczema?

A change in the Filaggrin gene that encodes for a structual protein in the skin


Genetic tendencies can cause more IgEs to be produced when exposed to certain allergens


What is an allele?

Different forms of the same gene

Can be dominant or reccesive

Can predispose to disease --> usually mutated versions (eg, CF)


What is the screening that is done for CF?

Immunoreactive Trypsinogen (IRT) - Guthrie Test --> If positive, trypsingoen will be present in the blood, due to the duct in the pancreas being blocked


Genetic Screening --> For the most common genetic mutations


Sweat Test --> Cl- above 60mM = CF likely


What is the difference between Cyclin/CDKs and CKIs?

Cyclin/CDKs --> Cell growth promoters


CKIs --> cell cycle (growth) suppressors......there are 2 types.....

INK4/p16 --> Inhibit CDK4/6

CIP/Kip (p27) --> Inhibt all CDKs


Name 2 pharmacological approches for fixing the ASL in patients with CF

Calcium-Activated Chloride Channel (CACC) Activators 


Blocking ENaC --> Amiloride


How does 3 person IVF work?

The parents embryo is fertilised with the mans sperm

The parents embryo has their nucleus removed, and inserted into a donors embryo that has healthy mitochondria (and no nuclei)


What are Tumour Suppressor Genes?

Genes that exert negative effects on cell growth (eg, p53)

So mutations in these will cause an increase in cell growth!!


Usually recessive, so less likely to have full mutations


Explain how the differentation of embryonic stem cells occurs

ESCs will form embryoid bodies once they have stopped renewing (around 6 days)

These bodies have three germ layers (endoderm/mesoderm/ectoderm)

After another 10 days, with differentation factors, the specific cell is formed (for example a cardiomyocyte for the heart)


Explain siRNA mediated RNA interference

Short dsRNA (siRNA) binds to a specific part of an mRNA coding region --> Causing mRNA cleavage


What's the difference between Heterochromatin and Euchromatin?

Heterochromatin --> Densely packed (condensed) and not actively transcribed


Euchromatin --> Beads on a string apprearance and actively transcribed!


What are the 2 types of families of proteins involved in the cell growth cycle?


And where abouts are these used?

Cyclins --> Transcription dependent


Cyclin-Dependent Kinases --> Activation dependent

Usually by phosphorylation



What is a Single Nucelotide Polymorphism (SNP)?


And what criteria needs to be filled for something to be called an SNP?

A varation in a DNA sequence by a single nucleotide, at the same position, in the genome between members of the same species


The variation must occur in at least 1% of the population


Generically speaking.... if a molecule involved in cell growth starts with a p (eg, pRb/P53/P16) what do they do?

They inhibit cell growth (suppress it)


So mutations in these will cause an increase in cell growth


Where are endogenous steroids made?


And what different types are made here?

The Adrenal Cortex


Mineralcorticoids --> Aldosterone


Glucocorticoids --> Cortisol


What is a promoter?

A DNA sequence that determines the site of transcription initiation for an RNA polymerase /Transcription factors


What is the link between LL37 and Psoriasis?

LL37 is an endogenous antimicrobial thats needed to prtect the body when skin is broken

In psoriasis LL37 is overexpressed, allowing more to bind/activate dendritic cells --> Acts as an autoantigen

This triggers an immune response, which causes cytokines like IL-17 to be produced


What is NFkB?

Nuclear Factor of Kappa (light chain) in B cells


Causes the activation of inflammatory genes


Inhibited by IKb which binds across the Rel domain


What are the characteristcs of embryonic stem cells?


They will continue to proliferate almost indefintely


They will form tumours in immunocompromised rats


They are pluripotent


Alkaline phosphotase surface expression is exclusive to what type of stem cell?

Pluripotent embryonic stem cells


How does the CRISPR/Cas system work in bacteira to prevent viral infection?

Viral DNA is cleaved by the Cas complex, producing short spacer regions. These are then inserted into the CRISPR region of the bacterias genome.

The CRISPR is then transcribed and then pairs with TracrRNA to produce a dsRNA that is cleaved by endonuclease III. This produces (crRNA-tracrRNA) dsRNA sequances.

This binds to Cas9. This searches for matching DNA from viruses that matches the spacer regions. If found, it is destroyed.