Genetic Variation:

Genomics at the Molecular Level

DNA is only as powerful as the proteins it produces. Proteins are products of gene expression that create our phenotype. Some genes work alone producing a protein that results in a phenotype for a single gene trait. Other genes work together along with the environment to create a phenotype for multifactorial conditions. In this situation, a certain combination of proteins (gene products) cause one phenotype while a different combination of proteins from the same genes can cause a different phenotype, resulting in genetic variation for that trait or a trait that varies slightly from individual to individual. (Explained in the previous section, Multifactorial Traits) How can one gene produce different proteins for a given trait? One answer is that each gene has multiple alleles or variations in the DNA sequence at that gene locus, which is probably the result of mutations for that gene. Let's begin with DNA and look at how it directs the formation of proteins. Then, let us look at what happens when DNA mutates, what effect it has on the protein it produces, and how all of this leads to genetic variation for a single or multifactorial trait. Finally, let's look at microarrays, a wonderful technology that can identify genetic variation for a gene or group of genes, and will aide scientists in the diagnosis and treatment of those common chronic conditions such as heart disease, cancer, and diabetes. Let's begin with DNA.


Diagram of cell, chromosomes, DNA strand, and genes (with DNA sequence)

Image from the U. S. Department of Energy Human Genome Project

Genetics, DNA, and Heredity: The Basics: Look at the big picture and understand the basics.

Tour of the Basics: Brush up on your understanding of heredity, DNA, genes, traits, chromosomes and proteins at this interactive website developed by The Genetic Science Learning Center at the University of Utah.

DNA structure: Review your understanding of the structure of DNA and how it replicates as you build a DNA molecule at this interactive website developed by The Genetic Science Learning Center at the University of Utah.

Banana DNA Extraction: It is nice for your students to be able to see this substance we keep talking about in the study of genetics or genomics. They are surprised at what it looks like and that even under a microscope they can't see the individual molecule or the double helix. They always ask, "How do scientists know what it looks like?" Another teachable moment!


Protein Synthesis

Diagram showing protein synthesis

Image from the U. S. Department of Energy Human Genome Project

Protein Synthesis and Words by Lynn MarieWartski
Michigan Protein Synthesis Benchmarks
AAAS Benchmark 5C
National Science Content Standard C

Protein synthesis, the process of genes contributing to a phenotype, is complex and can be difficult for students to learn. Watching their teacher demonstrate their understanding of it while they teach is not enough for the students to truly understand what is going on at the cellular and molecular levels. They need to practice using these ideas, making mistakes and learning from them, in an environment with some support, before they are expected to use these concepts on their own when encountering new phenomena. This is a great activity to allow students to do just that as they work with a model of protein synthesis that involves their entire classroom. The teacher's desk is the nucleus containing the DNA sequences. In teams of 3, student 1 becomes the mRNA when they transcribe the DNA in nucleus and return to student 2, the ribosome. The ribosome (student 2) writes out the needed tRNA sequence to match the mRNA. Student 3, tRNA, looks for the correct sequence in the cytoplasm (classroom) and when they find it they flip up the card to reveal a word (amino acid). They return to the ribosome with their word (amino acid) to build a sentence (protein). The number of sentences you have your students work through would depend on when it takes them to get comfortable with this process before they move on to examine different types of mutations.

Transcribe and Translate a Gene: Practice applying your knowledge of protein synthesis at this interactive website developed by The Genetic Science Learning Center at the University of Utah.

How a Firefly's Tail Makes Light: Observe a real world application of protein synthesis as you watch the process in a step by step animation developed by The Genetic Science Learning Center at the University of Utah.

Alternative Splicing: How to Get More than One Protein from a Gene
by Lisa Weise, Lori Buwalda, and Barb Neureither
Michigan Protein Synthesis Benchmarks
AAAS Benchmark 5C
National Science Content Standard C

When teaching protein synthesis, you may want to use this activity if you go into more detail. Include the ideas that when the DNA is transcribed into RNA it must then have the sections that represent the introns removed leaving only the exons which makeup the mRNA(click here for more explanation and diagrams). As the human genome project progressed, scientists realized we don't have 100,000 genes as was originally thought. The new estimate became 75,000, then 50,000, then 35,000, and now around 25,000 (it may have changed since this was written). If that is true, then the idea that one gene makes one protein seems impossible since we have more proteins than genes. So how is this possible? Scientists now believe that a single gene can make multiple proteins by splicing together different combinations of their exons. That is what this activity is all about. Using the idea from the previous activity, Protein Synthesis and Words, they make their DNA sequence result in a group of words that can make more than one sentence (protein). By spicing out the introns (nonsense words) and combining different groups of exons (words) they end up with different proteins (sentences).


Mutations

Diagram explaning genetic mutations that may cause health issues

Image from the U. S. Department of Energy Human Genome Project

What is a mutation and how do they occur? (Genetic Science Learning Center, University of Utah)

What is happening at the molecular level when a mutation occurs?> See how this happens with the Slooze Worm Mutagenesis (Genetics Science Learning Center, University of Utah)

What Happened to the DNA? In this activity, we will use the three letter words in a sentence to model the effect of different mutations on a sequence of DNA and its resulting protein. All mutations are not alike; therefore the resulting proteins and phenotypes may differ due to genetic variation (multiple alleles) for that single gene. (Michigan Mutation Benchmarks - AAAS Benchmarks 5B and 6E - National Science Content Standard C)

Mutate a DNA Sentence! After identifying the reading frame in a DNA sequence, you determine the amino acid sequence and then try to create each of the mutations described at this website. Notice the impact each mutation has on the protein product and imagine the impact it could have on the phenotype for that trait. This is an event that results in genetic variation for that trait. Not all mutations will have the same impact on the trait and its phenotype. Developed by The Genetic Science Learning Center at the University of Utah. (Michigan Genetic Variation Benchmarks - AAAS Benchmarks 5B and 6E - National Science Content Standard C)

Sickle Cell at the Molecular Level, (modified from the activity at this website). In this activity, you will use your understanding of DNA structure, protein synthesis, and mutations to investigate the effect of a single nucleotide mutation in a single gene that results in a major change at the cellular level. (picture of healthy and sickled red blood cells) (Michigan Genetic Variation Benchmarks- AAAS Benchmarks 5B and 6E - National Science Content Standard C)

"The Meaning of Genetic Variation", NIH Curriculum Supplement Series, Human Genetic Variation, activity 2. This activity takes you a little further into the investigation of genetic variation using the disorder, Sickle Cell Anemia. It has the students look at the difference between a mutation in an intron and an exon. Then with the aid of a video titled, "What is Sickle Cell Disease?" and the Sickle Cell Database, both on the CD-ROM, the students answer a series of questions dealing with the cause of the disease at the molecular level, how it is inherited, and how you can determine if someone has the anemia or the trait through laboratory testing. They then apply their ideas for testing to determine if two individuals have the trait or anemia. (Michigan Genetic Variation Benchmarks - AAAS Benchmarks 1B, 5B, 5C, 6E, 8F - National Science Content Standards A and C and F and G)
View the entire module, Human Genetic Variation.

DNA Mutation Activity for Cystic Fibrosis: In this activity, students use their knowledge of DNA structure, protein synthesis, and mutations to investigate different mutations in the gene known to cause Cystic Fibrosis. This activity helps the students realize that you can have genetic variation within a single gene. That there are multiple alleles for most genes (in fact there are about a thousand alleles for the cystic fibrosis gene) each created by a different mutation for that gene. Some of the mutations cause a change in the protein product and some have no effect. (Michigan Genetic Variation Benchmarks - AAAS Benchmarks 5B and 6E - National Science Content Standard C)


Microarrays

DNA sequence as dot pattern

Image from the U.S. Department of Energy Genomics: GTL Program

How can we tell which genes are functioning in a given tissue or cell? How can you tell which genes are functioning in a cancerous tumor so that we can prescribe the best treatment?

DNA Chips: A Laboratory in the Palm of Your Hand: Read about this incredible technology, what it is, how it works, and how scientists will be able to use it to better diagnose and treat common chronic conditions such as cancer.

DNA Microarray Methodology: In this animation, you will need to use your knowledge of protein synthesis and DNA structure as you learn how DNA Microarrays are used in experiments.

DNA Microarray: During this virtual experiment you will use microarrays to look at the differences between healthy cells and cancerous cells at the website developed by The Genetic Science Learning Center at the University of Utah.

DNA Chips: This issue of the magazine Snapshots of Science and Medicine, includes a great explanation of DNA chips or microarrays. It also includes easy to understand student activities and a teacher's guide. I would strongly recommend printing the entire issue and teacher's guide and using the activities with your students so they can better understand this new technology. In the activities the students use their knowledge of the complementary structure of DNA and protein synthesis to simulate the use of a DNA chip to sequence an unknown strand of DNA and then in another activity they use a chip to determine which form of cancer several patients have by viewing which genes are active so they can prescribe the best treatment for the cancer. (Michigan Microarray Benchmarks - AAAS Benchmarks 6E and 8F - National Science Content Standards C and E)