monogenic disorders + cancer

Question 1

who invented the concept of ‘inborn errors of metabolism’?

Answer 1

Archiabald Garrod (1909)

Question 2

what is Alkaptonuria?

Answer 2

autosomal recessive mendelian trait
defect in the enzyme homogentisate 1,2 deoxygenate
this inactive enzyme leads to the accumulation of homogentistic acid in joints
→ causes cartilage damage and back pain

Question 3

what is the pathology of Alkaptonuria?

Answer 3

blackened urine (high levels of acid are excreted as kidney/prostate stones)
black spots in eyes → shows precipitation of acid

Question 4

the discovery of Alkaptonuria led to identification of other inherited metabolic disorders. Who by?

Answer 4

william bateson (1909)
began cataloguing human diseases that exhibited mendelian inheritance

Question 5

examples of autosomal recessive

Answer 5

alkaptonuria, sickle cell anaemia

Question 6

examples of autosomal dominant

Answer 6

brachydactyl (short phalangees)

huntingtons

Question 7

examples of X linked

Answer 7

muscular dystrophy, haemophilia

Question 8

associated with one of the 22 non sex chromosomes is what type of genetic inheritance?

Answer 8

autosomal

Question 9

X linked =

Answer 9

sex linked

only shown in males (daughters are carriers but won’t show the phenotype)

Question 10

explain sickle cell anaemia

Answer 10

linus pauling (1949)
SCA caused by SINGLE POINT MUTATION st position 6 of beta chain
changes glutamic acid → valine
causes change in shape of erythrocyte → sickle shape → due to large insoluble polymers formed

Question 11

what is haemoglobin made out of?

Answer 11

tetrameter of 2 alpha + 2 beta subunits

each subunit contains haem group of iron (4 molecules of iron per Hb)

Question 12

explain the epidemiology of sickle cell anaemia in sub saharan africa

Answer 12

2% prevalence
heterozygote carrier frequency = 10-40%
heterozygote = co dominance of sickle cell allele and normal Hb allele so exhibit intermediate sickle cell trait (less severe than homozygotes
show more resistance to malaria → beneficial mutation so survive and reproduce → heterozygote frequency is maintained

Question 13

______ allows chromosomes to be distinguished

genes can be mapped to specific chromosome regions

Answer 13

karyotyping

Question 14

porto-oncogenes are caused by a _____, _______ mutation

Answer 14

dominant

gain of function

Question 15

tumour suppressor genes are caused by a ______, ________ mutation

Answer 15

recessive

loss of function

Question 16

autosomal dominant, progressive, late onset, inherited

what disease is this?

Answer 16

Huntington’s Disease
( a neurodegenerative disorder)
dementia and movement loss → due to massive neuronal loss in basal ganglia and dilation of lateral ventricles

Question 17

explain how Huntington’s disease works?

Answer 17

in normal HD gene, there are 10-35 CAG (glutamine) sequences repeated
→ makes a wild type protein called polyQ10-35
in disease, expansion of repeated sequences in a row → 36-121 repeats
mutant polyQ26-121
makes mutant HD protein toxic to neurons → kills them

Question 18

what disease is X linked and causes progressive muscular damage and wastage?

Answer 18

duchenne’s muscular dystrophy

Question 19

when is muscular dystrophy most lethal?

Answer 19

childhood and early adulthood

Question 20

if duchenne’s muscular dystrophy is X linked who is affected?

Answer 20

mainly affects males as only 1 mutated X is needed for the disease
females with 1 affected X = carriers
2 affected Xs = have disease severely

Question 21

what position is duchenne’s muscular dystrophy gene on the chromosome?

Answer 21

Xp21

identified by DNA deletion

Question 22

how does muscular dystrophy happen?

Answer 22

deletion of part of the dystrophin gene (largest human gene)
(marker is therefore dystophin when comparing to standard)
dystrophin is a bridging complex connecting muscle fibres so without can’t maintain muscle integrity