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Anonymous
06-04-2004, 09:46 PM
Problem 7 Huntington's disease 1

The data below shows the results of electrophoresis of PCR fragments amplified using probes for the site which has been shown to be altered in Huntington's disease. The male parent, as shown by the black box, got Huntington's disease when he was 40 years old. His children include 6 (3,5,7,8,10,11) with Huntington's disease, and the age at which the symptoms first began is shown by the number above the band from the PCR fragment.

http://www.biology.arizona.edu/molecular_bio/problem_sets/Recombinant_DNA_Technology/graphics/07q.gif


What is the prognosis for the normal children 4, 6, and 9?
A. 4 and 9 do not have the trait, and will not get Huntington's disease, but 6 is likely to start the disease when he reaches his father's age of 40.
B. 4, 6, and 9 are lucky and have not inherited the defect causing Huntingtington's disease.
C. 4, 6, and 9 will still develop Huntington's disease at some point in their lives, since the disease is inherited as a dominant trait.
D. Two of the three will develop the disease, since it is inherited as a dominant trait, but the data does not allow you to predict which two.
E. 4, 6, and 9 must be children of a different father, and thus do not carry the trait for Huntington's disease.




Prognosis for children

During electrophoresis, fragments of DNA migrate through a gel with larger fragments moving more slowly. In Huntington's disease, PCR amplifies a region of the chromosome which has variable number of repeating CAG sequences. Normal individuals can have up to 30 copies of the sequence but individuals with Huntington's have from 37 to over a hundred.
In the gel showing results of the PCR experiment for a family with a father having Huntington's disease, children 4 and 9 show only normal sizes for this region, showing that they will not get the disease.

The normal individual 6 has amplified sequences similar to the diseased father, showing that he too will get Huntington's disease. The size of the CAG fragment correlates with the age of onset. Since the father got the disease at age 40, and child 6 has the same size of the fragment, we can suggest that he is likely to get Huntington's disease about the time he reaches 40.





ans 7:
A. 4 and 9 do not have the trait, and will not get Huntingtonss disease, but 6 is likely to start the disease when he reaches his father's age of 40.

Children 4 and 9 do not have an amplified CAG repeat, and their PCR product migrates with control normals. Child 6 is currently normal, but has an allele with approximately the same number of repeats as the father. Thus, you could expect the child to develop Huntington's disease when he/she reaches 40.





Problem 8: Huntington's disease



The data below shows the results of electrophoresis of PCR fragments amplified using probes for the site which has been shown to be altered in Huntington's disease. The male parent, as shown by the black box, got Huntington's disease when he was 40 years old. His children include 6 (3,5,7,8,10,11) with Huntington's disease, and the age at which the symptoms first began is shown by the number above the band from the PCR fragment.

http://www.biology.arizona.edu/molecular_bio/problem_sets/Recombinant_DNA_Technology/graphics/07q.gif



In the Figure showing data on Huntington's disease, which of the following conclusions is valid:

A. No relationship between age of onset of disease and the migration rate of PCR fragments.
B. A shorter PCR fragment predicts early onset of Huntington's disease.
C. Increased length of the amplified PCR fragment predicts early onset of Huntington's disease.
D. Huntington's disease must be contagious since many of the children have the disease.
E. None of the above.



Relationship between the number of CAG repeats and the age of onset of the disease

The PCR amplified region shows a correlation between size of the fragment, a measure of the number of times CAG is repeated, and the age of onset. Larger fragment size correlates with earlier disease.


ans 8:
C. Increased length of the amplified PCR fragment predicts early onset of Huntington's disease.
There is an inverse relationship between the number of CAG repeats and the age at which Huntington's disease begins.