CHEM 342 - Introduction to Biochemistry

Hemoglobinopathy Assignment - Due Last Friday of the Semester

Attention: This is not a typical writing assignment, so do not treat it as such. The intent is for you to do your very best work. The paper you turn in should demonstrate that you truly understand and can apply what you have learned in this course. It should reveal your ability to reflect on a scientific topic and communicate it visually and in writing to others in a meaningful context. It is an opportunity to display your ability to formulate and explore personal learning issues, to find and assimilate relevant information from the scientific literature, and then synthesize everything into a meaningful paper that is not just a term paper. If done well, you might want to include your paper in an online portfolio to demonstrate that you have achieved the standards expected of you at the University of Delaware. Every year, the best paper from the class is submitted for the Edward Rosenberry Undergraduate Writing Award.

Background for the Assignment: Linus Pauling introduced the concept of molecular disease by demonstrating that the gene for sickle cell anemia was directly related to a chemical alteration of hemoglobin in the red blood cells of affected individuals. A few years later, Vernon Ingram identified a single amino acid replacement at position 6 of the beta chains of sickle cell hemoglobin (HbS) and showed that the sequence of the remaining 145 amino acids of the beta chains and all 141 amino acids in the alpha chains of hemoglobin were unchanged compared to normal hemoglobin (HbA). Subsequently, others determined the exact nucleotide substitution mutation in the beta globin gene possessed by sickle cell patients.

These discoveries prompted a stampede of sorts to discover other hemoglobin variants and the corresponding mutations in DNA. There are now on the order of 1000 different mutations known to affect the amino acid sequence or production of hemoglobin. While many of these are single-nucleotide-substitution mutations, deletions, and insertions that have little or no clinical effects, the consequences of others vary from benign to severe, as in the case of thalassemias. Many medical biochemists have made a career studying these usually rare hemoglobinopathies.

Using a list of hemoglobinopathies (alpha-chain, beta-chain, thalassemias), pick an interesting example to investigate as the basis for a 5-10 page, double-spaced, well-organized report. Select a variant that no one else in class has selected. Your report should have the following elements:

Preparation for this Assignment:

Each group should arrange a time to meet for 30-60 minutes with Catherine Wojewodzki, a science librarian in 117C Morris Library (831-4240, or Cathyw at who is familiar with this project and can provide assistance in tracking down the information you need. In the past, students have had problems because they did not take full advantage of the resources available. You will need to develop these library research skills as part of your undergraduate education. (They go well beyond "Googling" the Internet.)

Cathy Wojewodzki normally likes to work with <12 students at a time. This year, there will be three consecutive time slots on Monday, April 11, 8:00-8:30; 8:30-9:00; and 9:00–9:30 AM.

Cathy will work with you on your actual Hb variants.  If you make your selection and get it approved before you attend this session, you will not have to repeat the work. Groups will meet in Room 116B in Morris Library Reference Room area and use the laptop computers in there. You are welcome to bring your own, if you prefer.

This assignment will be evaluated for its composition, content, clarity of presentation, and depth of your analysis. An "A paper" must go beyond simple reporting of information. For example, a molecular graphics representation of your hemoglobin variant showing the location of any mutational modification, but make sure it shows something worth seeing. Remember, this should be your synthesis of the information, not a paraphrasing words by others. Late papers will not be accepted without a grade penalty.

Other Options: Students who would rather explore aspects of hemoglobin function, evolution, or properties of unusual hemoglobins from other species may do so in consultation with Dr. White. There are related topics available such as Glucose-6-P deficiency (favism).

1. Nobel Prize winner, Max Perutz (1914-2002), spent 20 years working on the X-ray crystallography of hemoglobin before he finally determined its three-dimentional structure in 1957. There after he spent much of the rest of his life studying the structure of interesting hemoglobin variants. One strategy you might try is to search and examine the publications of Max Perutz on PubMed or the Web of Science. Remember, you can often get full text copies through the University of Delaware's electronic journal subscriptions. You may also find some of the sites linked to the course home page of use.

2. Log on to one of the protein data bases and explore their reference lists and tabulations of hemoglobin varaints. Some data bases include:
        NCBI (National Center for Biomedical Information),
        PDB (Protein Data Bank, or
        Swiss-Prot (Swiss protein data base).
Simply start your search at any of these by typing in "human hemoglobin" and follow the links of interest.

3. Feel free to discuss your ideas and any difficulties you have with me (Dr. White) preferably well before the due date..

Making your request: All requests must be cleared by sending an e-mail message to Dr. White who will check to be sure no one else in the class has selected the same topic. Your request should be brief but include the name of the hemoglobin variant, the nature of the mutation, at least two primary literature citations to relevant references, and any medical consequences of the condition. Selections should be made on or before the second Friday in April after Spring Break.  HbC and HbS are not available.

Hemoglobin variants requested as of 11:00 AM
, 15 April 2011. Student initials after variant.
Hb Lepore (Boston-Washington)- JMa Beta Chain Variants

Hb H - KHu Hb D-Los Angeles  - MW Hb Bruxelles - beta F42del - TPh Other topics
Hb Barts - AL Hb Raleigh beta V1A - EH Hb Korle-Bu - beta D73N - JQ Hb F - HK

Hb Deer Lodge - beta H2R - MWy Hb Providence - beta K82N - HS Erythropoetin - ME
Alpha Chain Variants
Hb G- San Jose - betaE7G - SS Hb Chesapeake - alpha R92L - VB Fish Hb - Root Effect - BB
Hb Taybe - alpha 38-39del - EB Hb Porto Alegre - beta S9C - RM Hb Gun Hill -  beta 91-95 del - AJ Hb evolution at high altitude - TPe
Hb G Philadelphia alpha N68K - JF
Hb Olympia - beta V20M - KHo Hb Nottingham - beta V98G - SL Methemoglobinemia - JR
Hb Q-Thailand - alpha D74H - CE Hb Strasbourg - beta V23D - JT Hb Koln - beta V98M - SK Hb-Band 3 interaction - MS
Hb Bibba - alpha L136P -  JZ Hb E - beta E26K - KB Hb O Arab - beta E121K - CH Leghemoglobin - CA
Hemoglobin H - Constant Spring alpha term142Q - MP Hb-C Harlem beta E6K&D73N - JB
Neuroglobin - JMc

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Last updated:15 April 2011 by Hal White [halwhite at]
Copyright 2011 Harold B. White, Department of Chemistry and Biochemistry, University of Delaware