In the paragraphs above, circle the correct answer (high or low, heterozygous or homozygous).
“Pharmacogenetics” by Jeanne Ting Chowning Page 8
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.
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 on the next page. Circle the area of the graph that might likely corresponds to Kevin’s TGN and enzyme activity levels. Explain why you circled that region.
“Pharmacogenetics” by Jeanne Ting Chowning Page 9
Case copyright held by the National Center for Case Study Teaching in Science, University at Buffalo, State University of New York. Originally published February 4, 2010. Please see our usage guidelines, which outline our policy concerning permissible reproduction of this work. Title block illustration, licensed, ©Scott Maxwell | Dreamstime.com.