Assignment 7

Translocation Mapping in the 21^st Century

You are rotating with Professor Carson O'Genesis in the cancer center at WashU. His lab has discovered a rare, aggressive form of leukemia. A fusion of chromosomes 10 and 2 is present in almost all cases of this particular cancer. Through spectral karyotyping, the lab has fine-mapped the translocation down to 2q34-36 and 10p14. Some forms of cancer are caused by neomorphic chimera proteins that result from in-frame translocations of two separate genes. Professor O'Genesis believes that the chromosomal fusion observed in his patients causes cancer by this mechanism.

You think that if the break point is indeed in two coding regions, you will be able to solve the problem in a few hours. You are armed with:

A. A list of ESTs obtained from a translocation-containing tumor.

B. The location of the translocation (given above).

C. Everything you've learned so far in Bio5488.

D. Knowledge that the EST library was created with a pUC19 vector.

Your job is to find the two coding regions that are fused in this translocation. Please turn in the answer with explanation of the steps you took in solving this problem. Also turn in any scripts and their output that you may have used.

Beware: EST data is often contaminated with junk that results from cloning artifacts.

Note: The list of ESTs we've given you is quite small. In real life, the list would be much larger and the computational time to solve this problem would be on the order of hours.

Hint: Remember there are lots of repeats in the human genome.

Also answer the following questions:

1.Given the two proteins fused in the translocation, does it make biological sense that this it is associated with leukemia? Why?

2.Recommend an experiment to confirm the translocation that you mapped in-silico.

The Homework would be due on Friday March 20