Solved) USMLE Genetics: Updated A + Guide Solution:
Updated
What are the three things a USMLE question about genetics will ask you to do using
a pedigree? - ANSWERRecognize 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? - ANSWERMultiply 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 - ANSWERX 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? - ANSWERNormally 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? - ANSWERThe 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
What are two examples of disease that exhibit variable expression? - ANSWERNF1
and Hemochromatosis...manifestation depends on how much iron you accumulate
and how much you lose.
What is Imcomplete Penetrance? - ANSWERWhen 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? - ANSWERA 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?
- ANSWERBOTH genes must be mutated to get the symptoms. If you inherit one
mutation, you have a 90% chance of acquiring another...Imcomplete penetrance.
, What is a loss of heterozygosity? - ANSWERWhen 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? - ANSWERMultiply their risk of GETTING the
mutation by the penetrance, 90%.
What is pleitropy? - ANSWERThe 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)
What is Locus heterogeneity? - ANSWERWhen 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? -
ANSWERA 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? - ANSWERWhen 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?
- ANSWERTry Hunting MY FRIED Eggs (X)
TRI-nucleotide
Huntington's
Myotonic Dystrophy
Friedrichs ataxia
Fragile X
How will imprinting likely show up on the USMLE? - ANSWERManifestation of TWO
DIFFERENT DISEASES depending on whether the chromosome or gene deleted came
from the mother or the father.
What is Imprinting? - ANSWERWhen 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.
What two genetic diseases are classic examples of imprinting defects? -
ANSWERPraderWilli---Deletion of normally active Paternal gene
AngelMan Syndrome--Deletion of normally active Maternal gene
Updated
What are the three things a USMLE question about genetics will ask you to do using
a pedigree? - ANSWERRecognize 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? - ANSWERMultiply 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 - ANSWERX 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? - ANSWERNormally 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? - ANSWERThe 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
What are two examples of disease that exhibit variable expression? - ANSWERNF1
and Hemochromatosis...manifestation depends on how much iron you accumulate
and how much you lose.
What is Imcomplete Penetrance? - ANSWERWhen 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? - ANSWERA 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?
- ANSWERBOTH genes must be mutated to get the symptoms. If you inherit one
mutation, you have a 90% chance of acquiring another...Imcomplete penetrance.
, What is a loss of heterozygosity? - ANSWERWhen 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? - ANSWERMultiply their risk of GETTING the
mutation by the penetrance, 90%.
What is pleitropy? - ANSWERThe 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)
What is Locus heterogeneity? - ANSWERWhen 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? -
ANSWERA 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? - ANSWERWhen 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?
- ANSWERTry Hunting MY FRIED Eggs (X)
TRI-nucleotide
Huntington's
Myotonic Dystrophy
Friedrichs ataxia
Fragile X
How will imprinting likely show up on the USMLE? - ANSWERManifestation of TWO
DIFFERENT DISEASES depending on whether the chromosome or gene deleted came
from the mother or the father.
What is Imprinting? - ANSWERWhen 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.
What two genetic diseases are classic examples of imprinting defects? -
ANSWERPraderWilli---Deletion of normally active Paternal gene
AngelMan Syndrome--Deletion of normally active Maternal gene
