Assignment 1

1 .		Select the Blood Samples view on the input screen for HemoglobinLab. Scroll down the Select Case list and choose patient Miriam Dembele. Read Miriam's case history. Note that her case history is consistent with increased resistance to malaria. Compare Miriam's blood sample with the healthy control sample. Are there any obvious differences? Select the Microscope view and make note of any obvious differences in red blood cell structure. Do any of the red blood cells show phenotypic characteristics of sickle-cell disease? If so, approximately what percentage of her cells show these characteristics? Record your observations below.
2 .		Select the Gel Electrophoresis view to examine the electrophoretic migration pattern for the b-globin subunits of Miriam's hemoglobin as compared with a control sample from a healthy patient. Is the migration pattern of Miriam's hemoglobin indicative of a mutation in one of her globin genes? Is Miriam homozygous or heterozygous for this mutation? Explain your answer.
3 .		Select the Peptide Sequence view. Click the Find Difference button to identify the amino acid change in Miriam's hemoglobin compared with the normal control hemoglobin. Note: The amino acid in position one is valine and not methionine which is typically the first amino acid for most proteins. This is because the protein is initially translated with a methionine at position one but this amino acid is later cleaved off of the protein. Therefore, the functional protein begins with a valine at position one. Differences in the amino acid sequence of Miriam's hemoglobin protein compared with the normal protein will align at the far left of the screen. Which amino acid has been substituted for in Miriam's gene? Note the position of this amino acid change. This will be important for identifying the position of the nucleotide change in the globin gene.
4 .		Select the Edit DNA Sequence view. Miriam's globin gene sequence appears, compared with the normal, wild-type globin gene sequence. First, you will need to locate the DNA sequence with the triplet ATG that indicates the position of the start codon that would appear on globin mRNA produced by transcription of this gene. You can do this either by scanning the gene by clicking on the double arrows or (more easily) by typing ATG in the Search window and hitting the return key. This will take you to the ATG with the A in nucleotide 87 outlined with a red box. Click on the Bracket Codons button to outline codons beginning at the ATG. Use the single arrow to advance to codon 6 (nucleotides 105–107). Click on nucleotide 106—it should now be outlined with a red box—and change the A to a T. Click the Translate button to see a comparison of your custom-mutated protein to Miriam's protein sequence and the normal protein. Is this mutation consistent with what you know about the most common mutation that causes sickle-cell disease?