17 Genetics In Medicine

Question 1

What is the sickle cell anaemia nucleotide change?

Answer 1

1. Change in beta chain gene
2. Single base change
3. A => T

Question 2

What amino acid changes in sickle cell anaemia causing the mutation?

Answer 2

1. Position 6 of AA

2. Glu => Val

Question 3

What affect does the change in AA (glu=>val) have?

Answer 3

1. Changes conformation of haemoglobin as glu and val have different properties
2. Glu is negatively charged and val is hydrophobic uncharged
3. Val causes beta chains in haemoglobin to form a sticky hydrophobic pocket by joining another hydrophobic tetramer.
4. Forms sickle shape

Question 4

What results from the sickle shape of erythrocytes in sickle cell anaemia?

Answer 4

Block microvasculae which leads to symptoms

1. Anaemia
2. Fever
3. Severe pain
4. Sudden death

Question 5

What levels change in blood due to sickle cell anaemia?

Answer 5

Haemolytic anaemia
As a result of spleen removing sickle RBCs
Jaundice as a result of excess bilirubin from excess breakdown

Question 6

How is sickle cell inherited?

Answer 6

Autosomal recessive

Question 7

What could be a drug target regarding sickle cell?

Answer 7

1. Protein BCL11A repressor
   - epigenetics therapy
   - the protein binds DNA and switches off gamma globin gene (HbF)
   - repressing it would keep foetal Hb and not allow beta Hb to exist therefore stopping SCA
2. Gene editing therapy
   - Haemopoeitic stem and progenitor cells with wild type beta globin gene could be engrafted into bone marrow make healthy RBCs

Question 8

What is the genetic change causing Huntingtons Disease?

Answer 8

CAG is a short tandem repeat (STRs)
Healthy gene - 10-26 STRs
Mutation - 37-80 STRs in HTT gene

Question 9

How is Huntingtons disease inherited?

Answer 9

Autosomal dominant

Question 10

What physical effects does huntingtons disease have ?

Answer 10

Inherited neurodegenerative disease
Seizures
Abnormal gait (manner of walking)
Personality change
Dementia

Question 11

What is the general theme with huntingtons disease and age?

Answer 11

More CAG STR’s, lower age of onset!

Note. Although age of onset affected multifactorially. We know one gene on chrom 9 and two on chrom 15 but yet to find specific genes

Question 12

How can you test for huntingtons diseasE?

Answer 12

PCR can be used to amplify CAG repeat and compare normal using gel electrophoresis

Larger will migrate slower, smaller will migrate faster (Faster would be normal)

Question 13

Genome sequencing useful because?

Answer 13

• can identify genes where mutations can cause developmental disorders
• allow screening for de novo mutations in these genes
• BUT not at solution as even health people vary in DNA!