15/ human genetics 2 Flashcards
(16 cards)
info on Huntington’s disease, when does it onset, dominant/recessive, numbers affected, what is it
- late onset
- autosomal dominant
- 1 in 10,000
- progressive neurodegenerative brain disorder: neuronal death, cerebral atrophy, central nervous system disorder, uncontrolled movements, decrease in cognitive function, personality changes
what gene codes for huntingtons
HTT
huntingtons is a polyglutamine repeat disease. what does this mean, what does the number of repeats dictate, how do number of repeats change between generations
- HTT gene encodes a protein w a poly glutamine tract
- codon = CAG
- normal copies of the gene have less than 36 glutamine repeats, more than 36 repeats gives the disease
- number of repeats dictates onset of hd, more repeats = earlier onset
- CAG repeats are unstable and can expand on parental transmission
what happens from a mutated HTT protein w poly Q expansion
- likely to misfold and aggregate
- these proteins form inclusion bodies in neurons
- numerous downstream affects
info on cf, affected proportion, carrier proportion, what is it, how was gene identified, therapies
- 1 in 2000
- 1 in 22
- build up of mucus that can damage many organs
- cftr gene identified in positional cloning, like hd
- therapies: physio, DNase to reduce mucus viscosity, antibiotics and anti-inflammatory, mannitol spray to increase osmolality of mucus
importance of cftr gene
- transports cl- ions across plasma memb of lung lining cells
- ensures hydration of airways surface layer asl
mutations in cftr gene
- 70% of sufferers have delta F508
- 15 further account for half of remaining cases
- additional mutations are private mutations
what do dif cftr mutations result in, how do treatments differ
- dif molecular phenotypes
- type I - no protein
- type 6 - less stable protein
- treatment depends on this:
- class 4 and 6: potentiators to recover cftr function
- class 2 and 3: correctors improve processing of cftr
- class 1 and 5: production correctors, promote transcription of cftr for nonsense mutations eg
- for phe508del potentiator and corrector needed - orkambi treatment, £100k/year
duchenne muscular dystrophy info, transmission, onset, life expectance, symptoms
- x linked recessive disorder - only carried by mother (boys die too young)
- onset before 6
- 20-30 years
- symptoms: multisystem disorder, muscle weakness, wasting and atrophy, skeletal muscle degeneration, cardiac myopathy
dmd gene info
- largest known gene
- encodes dystrophin protein
function of dystrophin protein
- located primarily in skeletal and cardiac muscles
- in muscles part of protein complex that strengthens muscle fibres through linking muscle cells cytoskeleton actin to extracellular matrix connective tissue
what are 60% of dmd caused by, hotspot
- deletions of at least 1 exon
- deletion hotspot between exons 40-54
- deletions cause frameshifts
- premature stop codon massively shortens protein
why is beckers dystrophy similar but better than dmd
- also caused by mutation in dystrophin gene
- doesnt insert stop codon (dmd does), reading frame is preserved
- shortens protein but not as much as dmd
how is dmd treated
- anti-sense oligonucleotides
- forces splicing machinery to splice together exon sequences either side of the mutation - retain reading frame
- therefore presents as beckers dystrophy
how has identification of the gene and variants helped in single gene disorders
- diagnosis and carrier status
- prognosis
- tailored treatment
how will future ngs help single gene disorders
- identification of genetic determinants in novel conditions, characterised disorders, atypical presentation of a disease
- analysis of genetic determinants of complex disorders
