IAS02

Question 1

monogenic disorder

Answer 1

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

Question 2

monogenic disorder rarity

Answer 2

very rare individually, 1/1k collectively

Question 3

Hb structure

Answer 3

tetramer (heterotetramer), alpha 2 beta 2

Question 4

Hb genes

Answer 4

alpha: 1x HbA1, 1x HbA2 (identical exons)
beta: HbB

Question 5

sickle cell disease genetic

Answer 5

A->T, Glu -> Val at position 6 (hydrophilic -> strongly hydrophobic)

Question 6

sickle cell disease mecha

Answer 6

(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

Question 7

sickle cell disease symptoms

Answer 7

low RBC no., jaundice, periodic pain, repeated infections

Question 8

sickle shape cells effect

Answer 8

remain sickle shape in high O2 tension -> low O2 carrying capacity -> disrupted function & disease e.g. blood flow blockage

Question 9

SCD population

Answer 9

higher in africa than everywhere else

Question 10

heterozygous advantage

Answer 10

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.

Question 11

thalassaemia genetics

Answer 11

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

Question 12

thalassaemia effects

Answer 12

less func. genes, less proteins -> less Hb to carry O2 -> anaemia

Question 13

CF population

Answer 13

common in europe/us, less in china

Question 14

CF symptoms & treatment

Answer 14

salty skin, poor growth, thick sticky mucus, chest infections
NO treatment only management

Question 15

cystic fibrosis genetics

Answer 15

autosomal recessive
delta F 508, loss of 3nt -> 1AA
nonfunctional CFTR cannot transport Cl- across membrane -> electrolyte imbalance
(heterozygosity overrepresented in those w/ asthma, may stay in pop. be due to hetyerozygous advantage)