L9 - molecular mechnaisms of mendelian disorders Flashcards
(29 cards)
eg of a quantitative lof disease
loss of a pr product
thalessemia
describe the genetic of thalessemia
auto rec
both a and b typess
point mut or del
in greek cypriot high incidence in gene inv in rna splicing
describe the ptype result fom the lof mut in thalessemia
decr rate of synth/no synth of the globin chains that make up hb
mut in alpha globin chain - alpha thalessemia
eg of a qualitative lof disease (pr present but loss of qual/fucntion)
sickle cell anaemia
describe the genetic of sickle cell
auo rec
mut a single chnage in beta globin gene at codon 6 gag to gtg
describe the ptype of sickle cell
the mut results in the beta globin chains sticking together
this distorts rbc into a sickle cell shape and reduction in flexibility
can lead to microvascular thrombosis
eg of a disease cause by mut in regulatory
haemophilia beta
describe the genetic of haemophilia beta
x lined rec
mut in promoter factor IX gene
the muts are in the binding sites for tf inc LFIA and HNF4 - haemophilia beta leyden
other muts in anrogen response element - haemophilia beta brandenburg
what eg of diseases caused by large deletions
duchene muscular dystrophy
becker muscular dystrophy
what gene effected in duchene muscular dystrophy (dmd)
becker muscular dystrophy (bmd)
DMD gene
big over 2mbp
encodes dystorphin gene
a strucutral pr anchors contractile machinery to sacrolemma - makes a fixed but flexilbe strcutre for muscle contraction
what are the similarities in dmd and bmd
both x link rec
caused by del in DMD
both have ptype with progressive muscle weakness (same clinical)
differences in dmd and bmd occurence
dmd more common 1:3000
bmd 1:20000
dmd earlier onset ok up to 10 then wheelchair and dead by 30
bmd later and norm long life span
sim and differences in dmd and bmd genetics
in both 65% del of DMD
DMD gene 99% of it intron
no corr with size of del and severity of ptype
thought -
dmd- del that cause frameshifft - no dystorphin pr
bmd - del leave reading frame intact - smaller but functional pr
=
give eg of gain of fucntion disease
T cell acute lymphoblastic leukaemia
noonan syndrome
what the genetic of T cell acute lymphoblastic leukaemia
notch 1 mut in over half of patients
activated mut mut norm in heterodimerisation domain or c-terminal pest domain
what the genetic of noonan syndrome
muts inc PTPN11 codes oncogene shp2 phosphotase
sph2 regulate Ras/MAPK pathway inv in cell prolif/migr and apop
=imp in dev of heart/blood
what the clinical features of noonan syndrome
facial dysmorphology
short stature
heart defect
what are diseases of dominant negative effect
the mutated product interferes with the normal product prod in hetero
special case of lof
what genes often inv in syndromes of dominant negative effect
collagen genes
mut pr norm has dom negative effect on tiple helix assembly of the collagen fibre
eg of diseases of dominant negative effect
osteogensis imperfect type III
stickler syndrome
brain vessel disease
descibe osteogensis imperfect type III -
mut in cola1 or cola2
results in severe bone fragility/malform/ short stature
descirbe stickler syndrome
hereditry arthro-ophalamopathy mut in col2a1 inc splicing errors and smaller del distinctive facial abn / ocular problems retinal detachment and cataracts
describe brain vessel disease
mut in col4a1 disease
hemorrhagic stroke
ischeamic stroke
retinal arteriolar tortuosity
give eg of disease in which nature of the mutation effect the syndrome
haemoglobinopathy
notchopathy
