Globin Genes Flashcards
% of world population who are carriers for haemoglobin disorders?
5%
What is the general structure of haemoglobin?
Tetrameric protein: 2 alpha-like + 2 beta-like chains. 4 haem groups, each with an iron atom
How many molecules of oxygen can 1 Hb carry?
4 (1 for each haem group)
What are the embryonic haemoglobins?
Hb Gower 1 ζ2ε2, Hb Gower α2ε2, Hb Portland ζ2γ2
What is the foetal haemoglobin?
HbF α2γ2
What are the adult haemoglobins?
HbA α2β2, HbA2 α2δ2
Which Globin is the most important from foetus to adult?
Alpha globin as it is present in all haemoglobins
How are Globin genes arranged?
In clusters on chromosome 16, 11 (see if there are more)
Are all globin genes functional?
No, some are non-functional and are remnants of evolution
How many alpha and beta Globin genes are there in the diploid genome?
4 alpha
2 beta
What % of chains are affected in 1 beta-gene variant & 1 alpha-gene variant respectively?
50% beta
~25% alpha
S+S of sickle cell disease?
Abnormally shaped (sickled) RBCs, fingers of unequal and abnormal length, bony infarctions of phalanges and metacarpals MI, stroke, ulcers, heart failure
How does sickle cell disease lead to stroke?
Deoxygenated HbS forms roads and deforms cells -> sickled cells block capillaries (can’t squeeze through) -> MI
What is the treatment for sickle cell disease?
Folic acid (improve RBC production)
Antibiotics (fight infections)
Analgesia (combat pain of crises)
Hydroxyurea (reduce crises)
Kidney transplant and gallbladder removal
Wound care for ulcers, creams and surgery
Bone marrow transplant
What is the sickle variant?
Substitution of glutamic acid -> valine at AA 6 of the mature beta-chain