This material is replicated on a number of sites as part of the SERC Pedagogic Service Project
In this activity, students are assigned different alleles of the gene for phenylalanine hydroxylase to research using OMIM (Online Mendelian Inheritance in Man). Loss of this enzyme activity leads to accumulation of phenylalanine and the disease phenylketonuria (PKU). They are then asked to both explain and illustrate how this mutation may cause PKU.
The different alleles include point mutations, premature stop codons, frame shifts, deletions and loss of splice sites. By analyzing a specific allele, students are forced to follow the impact of the mutation through the DNA, RNA and protein. This exercise also illustrates that most genes have more than two alleles, in this case 67 have been identified.
Context for Use
Description and Teaching Materials
The PKU student assignment contains detailed instructions, a link to OMIM, a copy of the genetic code, the aligned DNA and protein sequences of phenylalanine hydroxylase and the structures of the amino acids. A second file contains an answer key for the instructors, along with a suggested grading scale (in our class the assignment was worth 8 points).
The PKU powerpoint slide is given to the students for them to use in answering their questions, and to illustrate the affect of their mutation on the DNA, RNA and protein. The DNA sequence contains both exons and introns (which should be removed in the mRNA). Point mutations should be indicated at each step in the central dogma (i.e. ATG to AUG to Met) and an explanation of the possible impact of this mutation on enzyme activity provided. For other mutations that change the size of the DNA, mRNA or protein, these should also be illustrated graphically by removing exons, or truncating the protein. Examples from a few groups of students are provided to get a feel of what a correct project would look like. PKU student assignment (Microsoft Word PRIVATE FILE 366kB May31 06) PKU answer key (Microsoft Word PRIVATE FILE 374kB May31 06) PKU powerpoint slide (PowerPoint PRIVATE FILE 21kB May31 06) PKU sample student answers (PowerPoint PRIVATE FILE 96kB May31 06) Assessment quiz (Microsoft Word PRIVATE FILE 56kB May31 06)
Teaching Notes and Tips
A collection of quiz questions were also provided under teaching materials. These can be used as a pre-/post-quiz, or incorporated into an exam.
References and Resources
MERLOT description of the "OMIM" (Online Mendelian Inheritance in Man) resource that is used in this activity.