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Problem 1
• James is the only person in his kindred
affected by DMD. He has one unaffected
brother, Joe. DNA analysis show that
James has a deletion in the DMD gene
and that Joe has received the same
maternal X chromosome but without a
deletion. What genetic counseling would
you give the parents regarding the
recurrence risk of DMD in future
pregnancy
problem 4 Chapter 12 text
Answer Problem 1
•
James may have a new mutation on
the X chromosome because Joe
inherited the same X chromosome
from his mother, and in neither the
mother nor Joe was the deletion
present. If this is the case, there is no
risk of recurrence. Alternatively, the
mother may be a mosaic, and the
mosaicism includes her germline. In
this case, there is a definite risk that
the mutant X could be inherited by
another son or passed to a carrier
daughter. About 5 to 15 present of
cases of this type appear to be due to
maternal germline mosaicism. Thus,
the risk is half of this figure for her
male offspring, because the chance
that a son will inherit the mutant X is
1/2x0.05 to 0.15 =2.5 to 7.5 percent.
Note DMD X-lined
If new mutation no risk
?
James
Joe
New mutation 10-4
same chromosome no mutation
If mother has germline mosaicism then 1/2x 0.05
to 0.15=2.5% to 7.5%
Problem 2
The beef gene is a located on chromosome 12. It is expressed in all tissues at high levels. The up gene is located on
chromosome 9 it is expressed only in liver cells in a cell cycle dependent fashion. The up gene contains two domains. Domain
1 contains a kinase which is important for cell proliferation. Domain 2 inhibits the kinase activity of domain 1 when it is
phosphorylated. The beef gene contains 3 domains all of which are a mystery. You receive some liver tumor cells.
Cytogenetic analysis indicates a chromosome translocation between chromosome 12 and 9. You also notice that the cell have
high levels of up kinase activity. From the diagram below draw one possible construct that may explain the presence of the
tumor and the increase kinase activity of up. From your hypothesis explain why up the cells are rampantly proliferating.
Chromosome 12
Beef promoter
Exon 1
Chromosome 9
Exon 2
Exon 3
Exon 4
Exon 5
Up promoter
Exon 1
Exon 2
Exon 3
Exon 4
Exons of up gene exon 5 contains domain 1 and exon 2 contains domain 2
Draw
Exon 5
Answer problem 2
From the diagram below draw one possible construct that may explain the presence of the tumor and the increase
kinase activity of up.
Chromosome 12
Beef promoter
Exon 2
Exon 1
Exon 3
Exon 4
Exon 5
Chromosome translocation
Chromosome 9
Up promoter
Exon 1
Exon 2
Exon 3
Exon 4
Exon 5
Exons of up gene exon 5 contains domain 1 and exon 2 contains domain 2
Chromosome 12
Draw
Up promoter
Exon 1
Exon 2
Exon 3
Chromosome 9
Exon 4
Exon 5
Before the translocation the up gene was expressed in a cell cycle and tissue specific dependent fashion. It also contained a
domain which modulated its kinase activity. The new up gene (a beef hybrid containing the up kinase domain) is now
expressed at high levels in all tissues and does not contain a domain 1 which functioned to regulate the protein. This protein
might stimulate cell proliferation in a cell cycle independent fashion resulting in a tumor.
Problem 3
• A patient with retinoblastoma has a single tumor
in one eye; the other eye is free of tumors.
• A. What steps would you take to try to determine
whether this was sporadic or heritable
retinoblastoma?
• B. What genetic counseling would you provide?
• C. What information should the parents have
before a subsequent pregnancy?
Text chapter 16 problem 1
Answer Problem 3
• A. What steps would you take to try to determine
whether this was sporadic or heritable retinoblastoma?
– Family history, careful examination of both parents retinas,
cytogenetic analysis if the tumor is associated with other
malformations, mutation identification.
• B. What genetic counseling would you provide?
– Advise parents of the risk, but point out that a future child could
be examined immediately after birth and at short intervals for
some time to make sure that if tumors develop, they are detected
and treated early.
• C. What information should the parents have before a
subsequent pregnancy?
– The parents should be informed of the risk of disease in
subsequent pregnancies, the availability of prenatal diagnosis,
and the impact of the disease should it recur.
Problem 4
• Suppose that you had the ability to introduce
normal copies of a gene into a tumor cell that
had mutations in the gene that caused it to
promote tumor growth
• a. If the mutations were in a tumor suppressor
gene, would you expect that these normal
transgenes would block the tumor-producing
activity of the mutations? Why or Why not?
• b. If the mutations were of the oncogene type,
would you expect that the normal transgenes
would block their tumor-promoting activity? Why
or why not?
Answer Problem 4
• a. If the mutations were in a tumor suppressor gene,
would you expect that these normal transgenes would
block the tumor-producing activity of the mutations? Why
or Why not?
– Mutations in a tumor suppressor gene are recessive and due to
loss of function. That function can be restored by the
introduction of a wild-type allele.
• b. If the mutations were of the oncogene type, would
you expect that the normal transgenes would block their
tumor-promoting activity? Why or why not?
– Mutations in an oncogene are dominant and due to gain of
function (over expression or misexpression). The normal
function will not inhibit these mutants, and the introduced gene
would be ineffective in restoring the normal phenotype