Authors of original unit: John M. Sabo, Jamie L. Lynch, and Deanna M. Raineri

Authors of spin-off: Ann Chen, Gloria Rendon, Johnny Tenegra, Chirag Kenia, David Kim.

Partner Projects: Biology Student Workbench, UIUC Biology Library

Grade Level: Sophomore, Junior, Senior students in Life Sciences

Subject Areas: Human Genetics, Genetic disorders, Sickle Cell Anemia

Unit Keywords: sickle cell anemia, human genetics, genetic disorders, hemoglobin, molecular biology, Biology Student Workbench , bioinformatics

The purpose of this tutorial is two-fold. Firstly, you will learn how to search databases for DNA and protein sequences, and how to align and manipulate these sequences. You will also learn how to view 3-dimensional structures of protein molecules using sequences that you find in the first part of this tutorial. Secondly, you will learn about the molecular biology of an extremely common and painful disease, SCD, from the findings of the bioinformatics exercises and from the results of the literature research.

• As a tutorial: If the goal is to expose students to the tools in the Biology Workbench, then skip PartII-a and follow the rest of the tutorial in sequential order

• As a lesson: If the goal is to ask students to produce a report on the molecular biology of SCD, Then skip Introduction and follow the rest of the tutorial in sequential order

Web browser (preferably Firefox), Acrobat Reader, Adobe Flashplayer, Realplayer, Shockwave, Javascript-enabled and JMol plugin. To find out which plugins are already installed on your mozilla/firefox browser, just type 'about:plugins' in address box. You can download each plug-in component from the links provided and you can test if your system support Javascript from here.

Introduction: In this section you will find background information on the sickle cell disease.

Part 1: In this section you will learn how to get started with the Biology Workbench; namely, opening an account, logging into your account, and creating a session (i.e. folder) to store your data.

Part 2: In this section you will learn how to search databases within the Biology Workbench for the DNA sequence for the wild type beta-globin and to store the results of that search on your session.

Part 3: Now that you have the wild type beta-globin sequence, you can use it to find the mutant beta-globin sequence. Because we know that the mutant beta-globin sequence differs from the wild type sequence by a single base, we can use the wild type sequence to search a database for sequences that are extremely similar (or homologous) to it. In order to carry out the homology search, you are going to use a tool called BLAST.

Part 4: In this section you will compare the two sequences, the mutant and the wild type, by aligning their residues using CLUSTALW. You will also learn how to identify conserved regions within the sequence.

Part 5: In this section you will learn how to translate a nucleic acid sequence into an amino acid sequence using SIXFRAME translation program.

Part 6: In this section you will learn how to explore the visual representation of the two structures and their corresponding amino acid sequences with JMOL