(Solved) USMLE Genetics
What are the three things a USMLE question about genetics will ask you to do using a pedigree?(Ans- Recognize a mode of inheritance Predict the recurrence risk of a disease, say in an unborn child Identify an OBLIGATE carrier for disease
How do you determine the probability of an unborn child being affected by an AR trait when you know the father is a carrier and the mother has probability X of being a carrier?(Ans- Multiply the odds of the baby being affected IF the mother was a carrier (1/4) by the chances of her BEING a carrier (X, or say 1/10)--- 1/40
How do you determine the probability of an unborn child being affected by an AR trait when you only know the Father has chance X of being and carrier and the Mother has chance Y of being a carrier (Ans- X time Y multiplied by the chances of being affected IF bother are carriers, which is 1/4 so X*Y*1/4
What is a manifesting heterozygote?(Ans- Normally X inactivation occurs in all cells of the female so one X works and the other doesn't. This is normally about 50/50 so even if half the cells dont make an enzyme, such as HGPRT, this is still enuf to get by ...IF in a rare case and due to bad luck all the good X-chromosomes get turned off...They will manifest the symptoms of HGPRT even tho they are a heterozygote
What does Variable Expression mean?(Ans- The nature and severity of a phenotype varies widely between individuals (often explained by the type of mutation to blame, missense v nonsense.) ALL people affected have symptoms
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What are two examples of disease that exhibit variable expression?(Ans- NF1 and Hemochromatosis...manifestation depends on how much iron you accumulate and how much you lose.
What is Incomplete Penetrance?(Ans- When some individuals who have the disease GENOTYPE do not manifest the disease phenotype for some reason... Degree of penetrance is used...90% penetrant is someone with a 90% chance of getting the manifestations.
How does incomplete penetrance manifest on a pedigree?(Ans- A skipped generation in an AD disease where the mother or father and children of a generation have the disease but the person does not.
What might be a reason for incomplete penetrance in Retinoblastoma, for example?(Ans- BOTH genes must be mutated to get the symptoms. If you inherit one mutation, you have a 90% chance of acquiring another...Incomplete penetrance.
What is a loss of heterozygosity?(Ans- When a normal heterozygote for a TUMOR SUPPRESSOR GENE gets a mutation in the remaining good gene, they become symptomatic and have 'LOST their heterozygosity.'
How do you determine the recurrence risk of an offspring developing a disease which is only 90 percent penetrant?(Ans- Multiply their risk of GETTING the mutation by the penetrance, 90%.
What is pleitropy?(Ans- The idea that 1 gene has more than 1 effect on the body (ie effect on more than 1 Part of the body...) Seen in Marfans, for example. (AD)
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What is Locus heterogeneity?(Ans- When one disease can be caused by mutations in more than one gene...OI or Albinism for example.
What might be asked regarding NEW mutations on a pedigree in the
USMLE?
(Ans- A new mutation will NOT affect siblings or their offspring (nieces, nephews) of the affected individual but THEIR OWN offspring are at risk for acquiring the new mutation.
What is anticipation?(Ans- When the severity of a disease worsens or age of onset of disease is earlier in succeeding generations....caused by triplet repeat expansion.
What are the 4 most commonly cited diseased that involve triplet repeat expansion?(Ans- Try Hunting MY FRIED Eggs (X) TRI-nucleotide Huntington's Myotonic Dystrophy Friedrichs ataxia Fragile X
How will imprinting likely show up on the USMLE?(Ans- Manifestation of TWO DIFFERENT DISEASES depending on whether the chromosome or gene deleted came from the mother or the father.
What is Imprinting?(Ans- When differences in phenotype depend on whether the mutation came from maternal or paternal origin...This is completely normal, until the gene that was not turned off gets deleted. Then there is absence of the gene from say the father, but the maternal gene was imprinted and turned off by methylation....no good copies are left.
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