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7 Cards in this Set
- Front
- Back
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What chemicals were found to do something to rats long ago? what condition was caused?
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cholesterol biosynthesis inhibitors were found to cause HOLOPROSENCEPHALY and genitourinary malformations.
Replacing cholesterol can rescue the phenotype. |
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Tell me about holopsencephaly: what are the symptoms and what gene is involved?
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midline defect, can be dominant, go from lethality to mild tooth weirdness.
happens with change in the normal ventral-dorsal orientation of the neural tube. Mutation is a result of changes in sonic hedgehog (SHH) - null SHH mice have HPE. SHH signals for the proper orientation of the neural tube. |
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How can errors in cholesterol cause HPE?
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HSS protein is made as a pro-protein, must be cleaved by cholesterol to its active form. So, mutations that keep cholesterol from forming stop SHH from working and result in HPE
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What's the one error of metabolism disease that ends up with physical dysmorphysm, what does it look like?
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Smith-Lemi-Opitz syndrome: mental retardation, cardiac anomalies, cleft palate/micrognathia, genital abnormalities.
BIGGEST INDICATOR = 2/3 partial toe syndactly |
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What enzyme is messed up in Smith Lemi Opitz, and what does their blood look like? Why does this cause HPE?
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Blood has decreased cholesterol but 100x elevation in plasma-7-dehydrocholesterol (the penultimate step in cholesterol synthesis) - so the mutation is in plasma 7 dehydrocholesterol reductase!
No cholesterol around = can't cleave SHH and don't get proper orientation of the neural tube. |
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What endocrine functions are messed up in smith lemi opitz, and why?
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ambiguous genetalia can be from lack of testosterone (produced from cholesterol)
cortisol insufficency may also be from lack of cholesterol. causes lack of growth and death. |
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Desmosterolosis: what's up?
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Also disorder of cholesterol metabolism. Causes profound microcephaly, downslanting palpebral fissures, flubfoot.
Desmosterol is an intermediate in biosynthesis of cholesterol, so build up = missing enzyme. Mutation in 24 DHCR Also results in SHH non-cleavage. |
