Genetics in Medicine

Question 1

What is the sickle cell nucleotide change?

Answer 1

change in beta-gene, 6th position: A –> T

Question 2

What is the sickle cell AA change?

Answer 2

Glu –> Val = Hydrophilic –> Hydrophobic

Question 3

In sickle cell what does the change in AA cause and how?

Answer 3

leads to creation of hydrophobic knob that can join with natural hydrophobic pocket (in B chains only) when Hb is in T state. Polymerised Hb causes cell to adopt sickle shape.

Question 4

What results from the sickle shape?

Answer 4

Block microvasculae and cause sickle cell crisis (lots of pain, downstream ischaemia). Crisis precipitated by factors that reduce O2 availability (so promote T state): smoking, obesity, cold, infection

Question 5

What change are seen in the blood due to sickle cell?

Answer 5

Haemolytic anaemia as a result of spleen removing sickled RBCs. Jaundice as a result of excess bilirubin from excess breakdown

Question 6

What is the benefit of having sickle cell trait?

Answer 6

no symptoms of SCA but conveys protection against malaria, very common in Sub-Saharan Africa

Question 7

How is sickle cell inherited?

Answer 7

autosomal recessive

Question 8

What could be a drug target regarding sickle cell?

Answer 8

Protein BCL11A repressor = binds DNA switches off gamma globin gene (foetal (gamma) globin)

Question 9

How could gene editing therapy be used to treat sickle cell?

Answer 9

Gene editing therapy = HSPC haemopoeitic stem and progenitor cells with wild type gene engraft in bone marrow –> healthy RBCs

Question 10

What is the genetic change that causes huntingtons disease?

Answer 10

CAG short tandem repeat, generally longer the repeat = the earlier the disease onset (however there is variation)

Question 11

How is huntingtons disease inherited?

Answer 11

Autosomal dominant