genetic diseases

Question 1

what are the symptoms of cystic fibrosis?

Answer 1

sticky mucus 
lung inflammation (chronic bacterial infections)
digestive disorders (pancreatic insufficiency)
male infertility caused by the absence of the vas deferens 
shortened life expectancy

Question 2

what is the mode of inheritance of cystic fibrosis?

Answer 2

autosomal recessive

Question 3

what gene does cystic fibrosis effect?

Answer 3

the gene encoding for cystic fibrosis transmembrane regulator

Question 4

what is the most common CFTR mutation?

Answer 4

F508del

Question 5

what kind of mutation is F508del?

Answer 5

in frame deletion

deletion of phenylalanine at position 508 in exon 10

Question 6

what are examples of point mutations in cystic fibrosis?

Answer 6

nonsense mutation G542X

missense mutation G551D `

Question 7

which mutation affects CFTR mRNA stability?

Answer 7

G542X nonsense mutation in exon 11
GGA to TGA
leads to mRNA degradation
no CFTR production causes a severe phenotype

Question 8

what mutation affects CFTR protein stability?

Answer 8

F508del
deletion of phenylalanine at the 508 position in exon 10
mRNA is translated but the protein is incorrectly folded
this causes the protein to be degraded
no CFTR produced causes severe phenotype

Question 9

how do some mutations affect the abundance of CFTR?

Answer 9

some mutations affect splicing
so only a proportion of transcribed RNA is correctly spliced
low levels of mature CFTR translated
less severe phenotype

Question 10

are the mutations involved in cystic fibrosis gain or loss of function mutations?

Answer 10

loss of function

Question 11

what are the possible treatments for cystic fibrosis?

Answer 11

physiotherapy to loosen mucus 
inhaled mucolytics to make mucus less sticky 
antibiotics to fight infections 
pancreatic enzyme supplements
CFTR potentiators such as ivacaftor 
CFTR correctors

Question 12

how does ivafactor work as a treatment for cystic fibrosis?

Answer 12

opens phosphorylated channels, even mutant ones, without the need for the binding of ATP
effective for treating cystic fibrosis caused by mutations like G551D that impair ATP-mediated channel regulation

Question 13

what is duchenne muscular dystrophy?

Answer 13

a genetic disease causing progressive muscle degeneration and weakness
first affects the muscles of the hips, pelvis, thighs and shoulders
causes wheelchair dependence in adolescence

Question 14

what is the symptom onset of duchenne muscular dystrophy?

Answer 14

early childhood

Question 15

what is the mode of inheritance of duchenne muscular dystrophy?

Answer 15

sex linked recessive

Question 16

what causes duchenne muscular dystrophy?

Answer 16

mutations in the DMD gene which encodes for dystrophin

Question 17

what is the normal function of dystrophin?

Answer 17

runs along muscle cell membranes helping to keep the muscle cells working correctly
it is part of a protein complex that strengthens and protects muscle fibres
anchors the cytoskeleton to other proteins in the ECM
transfers the force of contraction inside muscle cells outward to the cell membrane

Question 18

where is the hot spot for large deletions in duchenne muscular dystrophy?

Answer 18

between exons 44 and 55

Question 19

where is the hotspot for large duplications in duchenne muscular dystrophy?

Answer 19

between exons 2 and 10

Question 20

what are the most common point mutations in duchenne muscular dystrophy?

Answer 20

nonsense

Question 21

what are cellular consequences of loss of dystrophin function?

Answer 21

muscle cells become damaged as muscles repeatedly contract and relax with use
damaged fibres weaken and die over time leading to progressive muscle degeneration and weakness

Question 22

what are treatments for duchenne muscular dystrophy?

Answer 22

ataluren

a small molecule compound used for patients with nonsense mutations

Question 23

how does ataluren work?

Answer 23

when a premature termination codon is reached by the ribosome, ataluren recruits near cognate tRNA’s
these supress the nonsense mutation and allows the readthrough of the premature termination codon
allows the synthesis of full length protein

Question 24

what are clinical findings of ataluren in treating duchenne muscular dystrophy?

Answer 24

none of the children in the group taking ataluren lost ability to walk over the 48 weeks of the trial compared to 8% on the placebo
research predicts it could delay loss of walking for up to 7 years
but further work is needed

Question 25

what is huntingtons disease?

Answer 25

a neurological disorder causing ataxia, chorea, dementia and psychosis

Question 26

what is the mode of inheritance of huntingtons disease?

Answer 26

autosomal dominant

Question 27

what is the symptom onset of huntingtons disease?

Answer 27

late onset, middle age

shows anticipation

Question 28

what is the cause of huntingtons disease?

Answer 28

triplet repeat expansion at 4p16.3
CAG repeat
causes polyQ tail leading to neurodegeneration

Question 29

is the mutation involved in huntingtons disease a loss or gain of function mutation?

Answer 29

gain of function

Question 30

what causes trinucleotide repeat expansions?

Answer 30

replication fork slippage

Question 31

how are neuronal inclusions formed in huntingtons disease?

Answer 31

altered huntingtin protein gets cleaved by caspases
these cleaved fragments form aggregations called neuronal inclusions in the nucleus
there is a reduced expression of brain derived neurotrophic factor which is essential for neuronal survival
leads to neuronal death

Question 32

what part of the brain is most affected by huntingtons disease?

Answer 32

basal ganglia

Question 33

what is a possible treatment for huntingons disease?

Answer 33

IONIS-HTTRx

kills mRNA that carries the instructions for the damaged protein