Sickle cell anemia is caused by single base substitution mutation in the beta-globin gene
How?
17th nucleotide of the gene is changed from ‘A’ to ‘T’ on the non-template DNA strand
changes from: 5’ GAG 3’ to 5’ GTG 3’
results in: changes mRNA codon from 5' GAG 3' to 5' GUG 3', 6th amino acid changed from glutamic acid to valine
What is the mutant haemoglobin called?
Haemoglobin S (HbS)
Shape and how it relates to the function of normal RBC?
bi-concave in shape, move easily through blood vessels
How does sickle cells get their abnormal shape?
hydrophobic R group of Valine inserts into the hydrophobic pocket of another beta-globin, HbS crystallises to form long fibres at low oxygen concentration -> fibrous HbS protein causes RBC to assume sickle/crescent shape
Sickle-shaped cells do not move easily through blood vessels
sickle cells form clumps and get stuck in blood vessels
stiff and sticky
obstructs blood flow in blood vessels that lead to limbs and organs -> cause pain, serious infections, organ damage
sickle-cell beta0globin allele usually passed down from parent to offspring
