Part V – SNPs and TPMT
DNA techniques reveal TPMT gene is located on chromosome 6, is about 34 kilobases in length (34,000 DNA bases), and has 8 exons. An exon is a region of a gene that is present in the final functional transcript (mRNA) from that gene. The diagram below shows a representation of the TPMT gene, showing the exons as boxes. The first “wild type” is the most common version. In our case, the second version of the TPMT gene is associated with low enzyme activity (TPMT*3A) and has two single nucleotide polymorphisms (SNPs), or changes in single DNA nucleotide bases (from “G” to “A” in one case and from “A” to “G” in another) that result in different amino acids being inserted in the enzyme. This, in turn, affects the enzyme’s function. Over 20 different gene variants have been found, three of which are shown below.
Figure 5. Selected Human TPMT Alleles.
The wild-type human TPMT allele (TPMT*1) and variant alleles TPMT*3A, TPMT*3B, and TPMT*3C. Rectangles represent exons, with black coding areas and white untranslated regions. (Enlargement)
Source: Weinshilboum, R. (2001) Thiopurine pharmacogenetics: Clinical and molecular studies of Thiopurine Methyltransferase, American Society for Pharmacology and Experimental Therapeutics 29:601–605. Available online at http://dmd.aspetjournals.org/. This case is based on this article.
Questions
5a. Dr. Ryder now has the ability to conduct a SNP genetic test on her patients to determine what level of drug they should get. A new patient on the ward, Kevin, is homozygous for TPMT 3A*. The graph shown in Part III is reproduced below. Circle the area of the graph that might likely corresponds to Kevin’s TGN and enzyme activity levels. Explain why you circled that region.
5b.What level of the drug (low, medium, or high) should Dr. Ryder give him? Explain your answer.
5c. In your own words, summarize how knowing someone’s TPMT DNA sequence could be used to determine what kind of medical care they should receive.
Postscript
Dr. Ryder responded quickly to Laura’s drug reaction. She discontinued the drug for Laura. Laura’s condition began to improve rapidly!
Originally published at http://www.sciencecases.org/pharmacogenetics/case5.asp
Copyright © 1999–2010 by the National Center for Case Study Teaching in Science. Please see our usage guidelines, which outline our policy concerning permissible reproduction of this work.
