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) causes 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. (Developed 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, that are 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.
Image from the U. S. Department of Energy Human Genome Project
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
Image from the U. S. Department of Energy Human Genome Project
"Protein
Synthesis and Words," by Lynn MarieWartski - Michigan
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 what it takes to get them 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
Unviersity of Utah.
"Alternative Splicing: How
to Get More than One Protein from a Gene," by Lisa
Weise, Lori Buwalda, and Barb Neureither
Michigan Science 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 and 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).
DNAcode, a great tool developed
by Mike Huber.
DNAcode is a simple Word macro that allows you to transcribe
and translate DNA into RNA and Amino Acids (and back again). This easy
to use, free macro helps in creating worksheets and tests for students
as well as allowing students to quickly determine DNA sequencing errors
for lab reports and papers.
Image from the U. S. Department of Energy Human Genome Project
What
is a mutation and how do they occur? (GSLC, Utah University)
What
is happening at the molecular level when a mutation occurs?
See how this happens with the Slooze
Worm Mutagenesis (GLSC, Utah University)
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 Science 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 Science 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 Science 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 aide of a video titled, "What is Sickle Cell Disease?"
and the Sickle Cell Data Base, 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 the
anemia.
Michigan Science Benchmarks
- AAAS Benchmarks 1B, 5B,
5C,
6E,
8F
- National Science Content Standards
A and C
and F
and G
To download the lesson plan and copy masters click
here. It is Activity Two in the module. The instructions for downloading
are given at this site.
To view the entire module, Human Genetic Variation. Click
here
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 Science Benchmarks - AAAS
Benchmarks 5B
and 6E
- National Science Content Standard C
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, is an issue of the magazine
Snapshots
of Science and Medicene, that includes a great explanation
of DNA chips or microarrays. It also includes easy to understand student
activities and a teachers guide. I would strongly recommend printing the
entire issue and teachers 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 Science Benchmarks - AAAS
Benchmarks 6E
and 8F
- National Science Content Standards C
and E
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