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Human Genome
Project - Case Notes
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Notes
Author - Linda Hensel-Burke - Summer 1998
Background NHGRI: The Human Genome Project contains a general project description and links to more explantory material.
Teaching Notes
Day One. Introduction of the central dogma or how protein molecules that build all components of living systems are made from genes (DNA-->RNA-->protein). The students will build a DNA molecule in class from the DNA sequence you put on the board and see how it is made into a protein. They will also discover how a single base change can change the resulting protein. One of the outcomes of the Human Genome Project is to catalog genes to determine base differences that result in disease. Then scientists can determine how to combat or detect the diseases at a molecular level to reduce the harmful effects.
Homework Assignment for Day Two. This exercise provides basic background for the Human Genome Project from internet sources. The students will search the web using initial links and bring answers to assigned study questions to class. A class discussion should center around their findings.
Day Two. The exercise, "Finding a Gene in a Pile of Data" can be used to demonstrate the need for technological advances to keep pace with science. It has been estimated that 3-10 % of our genome actually codes for genes. The remainder of the DNA sequence is involved in packaging the DNA into chromosomes and additional roles that have yet to be determined by scientists. So, when scientists gather DNA sequence information, how do they determine where a gene is? In reality, computers are used to determine if a sequence contains a gene or not. In the class exercise students are given a lengthy piece of sequence and asked how they would determine if a gene is present.
Day Three. What is the large human genome data base used for? The exercise demonstrates the public availability of the DNA sequence data base and the types of information that can be gathered from it. Students are given a DNA sequence with the BLAST site internet address. This site uses computer-assisted DNA sequence analysis/comparisons to answer the following: the type of organism their DNA came from, the organisms it is related to, and what type of protein it encodes. A demonstration for interested faculty exists at
Human Genome Education Program
Day Four. Scientists working on the Human Genome Project have allocated 5% of the entire budget to deal with ethical issues. Students can visit the US Department of Energy's web site that contains abstracts for each of the "Projects in Ethical, Legal, and Social Issues"
A discussion can center around projects currently funded. What are they? Do they meet the needs of the public? I would have the students choose an abstract from a project that interests them and discuss it with the group (write a paragraph about it or both).
A second exercise involving ethical, legal, and social issues involves a class or small group debate on the issues at hand. The purpose of this exercise is to let the students determine how much scientific information they need to know in order to effectively debate an issue. The students can be assigned a pro or con article and asked to prepare themselves to argue that point the next class period. They should be asked to look up the necessary statistics, etc. to prepare an effective debate. We have used these issues in our nonmajors courses before and the students, in general, have lots of fun with them.
Day six. Venter et al. (1998, Shotgun Sequencing of the Human Genome. Science 280:1540) work for private companies--The Institute for Genomic Research and Perkin--Elmer. These authors have devised a method for sequencing the entire human genome in 3 years and have begun to do so. If successful, they will finish well before the academic laboratories funded and coordinated by the Human Genome Project (launched in 1990 and proposed completion in 2005). Are the duplicated efforts necessary? This article would be a good tool for generating a discussion about how tax dollars are used for science. What happens after money has already been allocated if the project is finished by someone else?
(back to top) The Central Dogma. Models are available From Linda Hensel-Burke (x2707) to work through this exercise (4 small groups). Give the students 4 bases (G, A, T, and C) that make up DNA and let them know that there are 20 different protein building blocks (amino acids). See if they can figure out how to get from the DNA bases to the protein building blocks in 10 minutes or so (pattern recognition). Many students may remember this from high school and might work through this in less than 10 minutes. Have those students explain the pattern (3 base code) to others in the group. Give the students the codon (3 base, Genetic Code Table) table and explain the universality of the code (all living organisms use this pattern to make proteins from genes). Write up the following DNA sequence on the board:
CCTGAAGAG
and have the students prepare a double-stranded DNA molecule (pattern 2--A always pairs with T and G always pairs with C). They can then make an RNA copy of the gene strand using the same "base-pairing" rules. Then the codon table should be consulted to create part of a protein (the model codes for part of the hemoglobin protein). Next, change one base of the DNA sequence:
CCTGTAGAG
and have them make the resulting protein (this is actually a part of the sickle-cell hemoglobin protein). Explain how a single base change can result in disease and these base changes can only be studied if scientists where the gene sequence is (hence, the need for the Human Genome Project).
(back to top) Finding a Gene in a Pile of Data Three DNA sequences have been downloaded from the DNA sequence data base and are available for you to copy for the students. One sequence is of a salmon melanin concentrating hormone gene, another from a human keratin gene, and another from a mouse actin gene (the genes themselves are not important for this exercise; you could download any gene sequence of interest to you or your class). Each group of students could receive a different DNA sequence. The students will have worked through the "Central Dogma" exercise and be familiar with the Genetic Code.
The students are asked to determine if the DNA sequence codes for a gene or not. Remind them that only 3-10% of the DNA bases code for proteins in the human genome. They are asked to produce in writing a method for determining if any DNA sequence is a gene.
Facts to feed to the students as they stumble and progress:
AUGCCU
The coding sequence could begin at A, U or G. The students may even come up with forward and backward and that would be ok too. In real life, however, the decoding machinery can only move in one direction on each strand due to the nature of the sugar-phosphate backbone.
The students may use the same sequence for the "Data Base Use" exercise. Each student can select a segment of 100 bases from the sheet of DNA sequence and enter into the blast program. The results will be mailed to their individual email addresses.
The reading frames for the following sequence are as follows:
5'ACGGTCGA
TGCCAGCT 5'
Reading Frames (each codon--3 letter code-- is decoded to one amino acid)
ACG GTC or CGG TCG or GGT CGA
TCG ACC or CGA CCG or GAC CGT
The students will have to look at all six reading frames to determine if it is a gene sequence or not. If stop codons are found in all six frames, then it isn't a gene sequence.
There are many computer programs available today that determine if DNA sequences code for genes and also predict the structure of the resulting protein that is coded for by the gene sequence. This exercise will demonstrate how technology has made gene searching possible i.e. ask the students to imagine searching for 100,000 genes in the human genome sequence by hand. It also demonstrates how finding one pattern (the DNA code)
Data Base Use. Students will be given one of five DNA sequences to enter into the BLAST program. They simply type in the DNA sequence and results are sent to their email address. They can bring the results with them to the next class period.