IAS02 Flashcards
monogenic disorders & rarity
10k+ diseases due to alterations in single gene
e.g. huntington’s (huntingtin), fragile X, hemophilia (CF8/9), tay-sachs (hexA -> hexoaminidase), SCD, thalassaemia, CF
very rare individually, 1/1k collectively
Hb structure & genes
tetramer (heterotetramer), alpha 2 beta 2
alpha: 1x HbA1, 1x HbA2 (identical exons)
beta: HbB
sickle cell disease genetic
A->T, Glu -> Val at position 6 (hydrophilic -> strongly hydrophobic)
sickle cell disease mecha
(valine pulled to center of heme) -> more hydrophobic interaction btn B chains -> tend to form strands -> align & crystallize to form fibers i.e. polymerization -> distorts whole cell shape from biconcave to sickle shape
sickle cell disease symptoms & population distribution
low RBC no., jaundice, periodic pain, repeated infections
higher in africa than everywhere else
sickle shape cells effect
remain sickle shape in high O2 tension -> low O2 carrying capacity -> disrupted function & disease e.g. blood flow blockage
heterozygous advantage
heterozygous selected due to reduced risk of infection / severe disease / death than homozygous (dominant) i.e. fitter, applies to SCD, G6PDD, thalassaemia
e.g. SCD: carriers 10x less risk of severe malaria, malaria selected HbS to remain in pop.
thalassaemia genetics
both autosomnal recessive
alpha
(3/4: carrier, asymptomatic)
2/4 func. HbA: with mild anaemia
(1/4: HbH disease w/ heavier anaemia, microcytosis, hypochromia)
0/4: leads to hydrops fetalis, FETAL DEATH
beta
(1/2 func. HbB -> mild anaemia)
0/2 -> severe anaemia
thalassaemia effects
less func. genes, less proteins -> less Hb to carry O2 -> anaemia
cystic fibrosis symptoms & treatment, population
salty skin, poor growth, thick sticky mucus, chest infections
NO treatment only management
common in europe/us, less in china
cystic fibrosis genetics
autosomal recessive
delta F 508, loss of 3nt -> 1AA
nonfunctional CFTR cannot transport Cl- across membrane -> electrolyte imbalance
