L9 - molecular mechnaisms of mendelian disorders Flashcards Preview

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Flashcards in L9 - molecular mechnaisms of mendelian disorders Deck (29):

eg of a quantitative lof disease
(loss of a pr product)



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



desrcibe symptoms of haemoglobinopathy

from anaemia to symptomless
the most common mut is a gllutamic acid to valine - sickle cell
other aa sub decr the hb synth /instability of hb mol
some have high oxygen affinity


describe the genetics and ptype of notchopathy

mut in HD PEST domain in notch - GOF
mut in other region of notch - aortc valve disease


how can geentic background effect disease

polymorphs of the same gene may influence on disease ptype
modifying genes


give an eg of a polymorphs of the same gene influencing disease ptype

polymorph H558R has mut specific effect on SCNC5A related suck sinus syndrome


give eg of modifying genes effecting disease ptype

alpha thalessemia and beta thallesemia inhibit together
in alpha thaa excess alpha chain damages red cell precursors
coinherit a thal ameliorates b thal ptype