FRCPath part 1 MISC

Question 1

What are 7 ways a pre-mRNA might be alternatively spliced ?

Answer 1

Exon skipping, alternative promoter, alternative poly-A site, intron retention, mutually exclusive exons, alternative donor (5’) splice site, alternative acceptor (3’) splice site

Question 2

Why does the Beta-globin gene provide an example of an exception to the nonsense-mediated decay rule ?

Answer 2

Mutations which create a PTC (premature termination codon) in the first exon, which would normally be expected to activate NMD, do not do so if they are located from codons 2-23, whilst those found from codon 26 down cause NMD as expected. The capacity to reinstate translation from a downstream start codon has been shown to be the likely explanation for the ability to bypass NMD in this case.

Question 3

How do miRNAs function?

Answer 3

They bind complementary sequences within the 3’ UTR of target mRNA then:

(1) Inhibit translation by preventing binding of the translation machinery or
(2) Promote mRNA degradation (e.g. through deadenylation of the PolyA tail).

Question 4

How does bisulphite modification of DNA enable methylation detection ?

Answer 4

Unmethylated cytosines in DNA are converted to uracil through treatment of single stranded DNA with sodium bisulphite which causes deamination

Question 5

Name 3 categories of 3rd gen sequencing technology

Answer 5

sequencing by synthesis, nanopore, synthetic (based on existing short-read technology)

Question 6

What is PAGE and how good is its resolution ?

Answer 6

Polyacrylamide gel electrophoresis. Can resolve DNA molecules that differ as little as 0.2% (e.g. 1bp in 500bp)

Question 7

Which is the most common breakage syndrome ?

Answer 7

Fanconi anaemia

Question 8

The majority of small supernumerary marker chromosomes are derived from ?

Answer 8

…the short arms and pericentromeric regions of acrocentric chromosomes, particularly chr15 or 22

Question 9

RET LOF mutations cause… ?

Answer 9

AD Hirschsprung disease

Question 10

Name a disorder cause by a Telomerase defect

Answer 10

Dyskeratosis congenita: abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa

Question 11

Name 6 major types of enzymes involved in DNA replication

Answer 11

DNA Polymerase, Helicase, Primase, Topoisomerase, Telomerase, DNA ligase

Question 12

DNA polymerase synthesises DNA in what direction?

Answer 12

5’ to 3’

Question 13

Bloom syndrome is caused by a defect of which enzyme involved in DNA replication ?

Answer 13

Helicase

Question 14

Name a dominant disorder in which PTC variants lead to NMD but result in a milder phenotype than non-PTC variants

Answer 14

Marfan syndrome (FBN1 gene) - due to dominant -ve disease mechanism

Question 15

Name a dominant disorder in which PTC variants lead to NMD and result in a more severe phenotype than non-PTC variants

Answer 15

Duchenne muscular dystrophy (DMD gene)

Question 16

Describe what constitutive heterochromatin is

Answer 16

Permanently condensed/inactive, late replicating, darkly stained by C-banding, accounts for ~6.5% (200Mb) of the human genome, largely consists of AT rich, genetically inert satellite DNA