1.2 X -linked Flashcards
x vs y chromosomes
x chromosomes has many important genes in addition to gender determinants but Y-chormosomes are mostly just for gender
x linked diseases
mostly seen in males, female carriers normally don_t present, 50% chance for male to get disease from heterozygous mother
y chromosome
mostly strictly involved in determination of male gender by inducing testicular development. If testicular development is disrupted in early development, female phenotype is born
x linked disorders are
always expressed in males
x linked dominant
rare–expressed in females, half of cells affected (inactivation of one x chromosome in every cell); storage diseases G6PD deficiency
x linked recessive
more common–duchenne muscular dystrophy hemophelia
y-linked
no recorded y-linked diseases – affected male does not transmit to sons but all daughters are carriers; female carrier transmits diseases to 50% of sons and transmitts a carrier state to 50% of daughters
female may suffer partial disease bc of
mosaicism for x-chromosome –>lyon hypothesis meaning random inactivation —sometimes there is a preferential activation and you can have some expression of disease but that’s not common
G6PD def
makes red cells prone to lyse under oxidant conditions, females will lyse half the cells, males will lyse all the cells, so you’ll see the disease in both but to different extents – remember this is an AD disease
x-linked father transmistion
does not transmit to sons, but transmits to all daughters
x-linked mother transmition
50% of sons get the disease and 50% of daughters get the carrier state
x-linked dominant fater tramission (rare)
all daughters, none of sons
x-linked dominant mother transmission
50% of sons and daughters
x-linked dominant disorders
hemophilia, chornic granulomatous disease, Duchenne M.D., fragile x
Hemophillia A
factor 8 deficiency - most common inherited serious bleeding disorder - numerous mutations - most severe cases have large DNA inversion and no factor 8 is produced
Hemophillia A severe, moderate, slight
1% 2-5% 6-50%
Clinical course of hemophilillia A
from profound bleeding to minor symptoms, easy bruising and bleeding into areas prone to trauma (joints), hemarthrosis may be crippling, bleeding time and PT normal, PTT elevated, Treatment: factor 8 injections, comlications with anti 8 antiboides and AIDS
bleeding time
the time it takes to stop bleeding after a standardized cut. It is a measure of platelet fn
prothrombin time looks at
extrinsic pathway – 7–>10
partial prothromboplastin time (PTT) looks at
intrinsic pathway – 12-11-9-10
Hemophillia B
christmas factor 9 deficiency – clinically same as A
Ehlers-Danlos syndrome
complex disease affecting collagen synthesis – heterogenic disease w/ over 10 variants –all 3 modes of inheritance are seen – organs rich in collagen, skin, joints, and ligaments most frequently involved
Ehlers Danlos syndrom clinical features
since collagen lacks normal tensile strength, skin stretches and joints are hypermobile to gortesque proportions – contortionists – leads to serious complications including rupture of bowels and aorta
collagen synthesis
alpha chain synthesis, hydroxylation, glycosylation, alpha chain arrangement, triple helix formation, clipping of N and C terminal peptides, crosslinking
Ehlers Danlos syndrome type 6
recessive loss of lysyl hydrolase affecting hydroxylation, collagen types I and III, rupture of cornea and retinal detachment
Ehlers Danlos syndrome type 4
dominant negative defect in alpha chain, collagen type III, rupture of vessels and intestines
Ehlers Danlos syndrome type 7
dominant negative change in alpha chain that resists peptide cleavage, Type I collagen –> alpha chain synthesis and clipping of N and C terminal peptides are affected
Ehlers Danlos syndrome type 9
defect in copper binding protein that reduces activity of lysyl oxidase. On x-chromosome so x-linked –>affects crosslinking