Using Genetic Disease to Understand Genotype to Phenotype
Or
Freckles, Farts, and Earwax
I. Introduction: How does genetics determine our traits? We all know that our DNA
contains genes that control our traits--or phenotype. Let's look at some specific examples to
see how genes can control traits.
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We will use the 23andme companies website to help us understand more about
what genes are and how they control traits. They are a company that does human
genetic analysis quickly and inexpensively. Their website is at
https://www.23andme.com/
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To use the site, let’s register at: https://www.23andme.com/user/signup/
How Does it Work?
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Currently, the least expensive and most common way to obtain a genetic profile is to
look at key changes in the genome (our complete DNA sequence) that are known to
be linked to phenotypes (which are your observable traits), such as diseases or
other interesting traits.
We can also use these changes to trace ancestry--the more closely related two
individuals are, the fewer differences they have in DNA sequences.
These differences in DNA sequence between us are often single base changes and
these are called SNPs (pronounced “snips”, short for Single Nucleotide
Polymorphisms). SNPs can occur anywhere in the genome. 23andme looks for
SNPs that are in or near important genes—differences in SNPs at individual genes
help us identify which alleles (versions of the gene) we each have. We’ll learn more
about what these are below!!
One of the most important things to realize is that many of the bits of DNA sequence they
examine only point to an increased chance of getting a disease or having a trait--not that
you necessarily will!
1. Would you like to know that you have a slightly increased chance of a deadly
disease?
2. Would you like to know that you have a greatly increased chance of getting an
untreatable disease? How might knowing this affect you?
This is something to think about before having your genotype analyzed! The time is
very rapidly approaching that we will all know our DNA sequences and know the chances
that we will come down with a wide variety of diseases during our lifetime. Genetic
counselors can help us all understand what all of these predictions mean for our lives.
Consider a career as a counselor if this field sounds exciting for you.
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Let's get to the genes! Let’s take a look at the "What are Genes" video on the 23andMe site
and try to answer the following questions. The video is located at
https://www.23andme.com/gen101/genes/, or it can also be found under “Featured
Content” on the welcome page if you’re logged in.
3. How many genes do the 23andMe folks say that we have? (Their number may be a
bit low.)
4. How long is all of the DNA in a single cell?
5. What percentage of our DNA do we share with the rhesus monkey? Chimpanzees?
6. What percentage of our DNA sequences do we share with other humans?
7. All of our nucleated cells have the same DNA. What makes cells different from each
other? (Hint: are all genes on all of the time?)
II. How do genes control heredity?
DNA  RNA  protein
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We have one set of chromosomes for our mom and one from our dad.
RNA molecules are copied from the parts of our DNA that are genes (much of
our DNA isn’t genes). This process is called transcription and we say RNA is
transcribed from DNA. RNA is the same type of molecule as DNA—they both are
nucleic acids and are each composed of four nucleotides. These are the letters of the
genetic code!! ACG and T are the four nucleotides (also called bases) in DNA and
ACG and U are the four in RNA.
RNA copies are translated by ribosomes that use the RNA sequence to produce
proteins based on the RNA sequence code. We call this translation because it is
changed from the language of nucleic acids to the language of proteins.
Ribosomes read the DNA sequence in codons that consist of three nucleotides.
Codons specify the amino acid that is added to the growing protein by the ribosome.
There are codons that tell the ribosome where to start (AUG) and where to stop
(TAA, TAG and TGA). The genetic code is shown on the last page of this handout.
It is the RNA and proteins encoded in our DNA that make us what we are! It is slight
differences in our DNA sequences that make us different. Many of the differences
between humans are changes in a single base—that is, a single letter of the code is different.
These are the Single Nucleotide Polymorphisms, or SNPs for short, that are mentioned
above. These SNPs (pronounced snips) can be in or near a gene and they often show us
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what traits we will have. It is relatively easy to determine what our individual sequences
are at very many of our SNPs—this is our genotype. For example, 23andme surveys many
of our SNPs for just $100. Very soon we will be able to get the entire sequence of our
genome for not much more than that! Here is a video at 23andme explaining more
about SNPs: https://www.23andme.com/gen101/snps/ Let’s take a look.
Now is a good time to try to find SNPs and see how they can affect proteins:
Here are sequences of a short part of a gene:
AUG GUG CUG UCU CCU GCC GAC AAG ACC AAC GUC UAG GCC GCC
AUG GUG CUU UCU CCU GCC GAA AAG ACC AAC GUC AAG GCC GCC
8. Is this an mRNA molecule or DNA molecule? How can you tell?
9. How many SNPs can you can find in this segment? Circle those.
10. Use the genetic code at the end of this handout to translate this sequence into
amino acid sequence. Fill in the correct amino acid below each codon above.
11. What affect does each SNP have on the protein sequence? Do you think these will
affect the protein’s function? Why?
III. Let’s look at some examples of how genes and SNPs determine our traits:
Earwax...hey, get your finger out of your ear! Have you noticed what your earwax is like?
There are two major types of earwax, moist and dry. The 23andMe site describes some of
the biology and genetics behind earwax.
You do need to be logged in to view Health Reports. From the welcome page once logged in,
click on “My Results” at the top of the page and then on “Traits” in the dropdown menu.
Next scroll down to “Earwax Type”
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Here is some of the genetic info:
The genotype column shows the nucleotides at a single position in our DNA. This is a site
that has been identified to be important for this trait for which our sequences differ. Since
these genes differ at this site these are different alleles. These are examples of single base
changes (Single Nucleotide Polymorphism or SNPs). The “What it Means” column shows the
expected phenotype.
12. The genotype that is shown represents the sequence at a single base in our DNA.
Two bases are shown for this site (C or T). Why are there two bases listed as the
genotype?
13. So, these SNPs represent two different alleles of this gene. Think about Mendel's
experiments (Gregor Mendel...not Greg Mendel whose genotype is given here.)
Which of these alleles is dominant? Why do you conclude that?
14. Can you think of how earwax might be made by your body? Write at least one
possible explanation here (hint: it is made inside cells first before it ends up in your
ear canal).
15. If a material such as earwax is made in a cell it needs to somehow get across the cell
membrane. Do you know some of the ways in which cells move materials across
membranes? Describe how this could occur.
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16. If you scroll down a bit to “Learn More About ABCC11” you can see that the SNP
here is in the gene ABCC11. This gene encodes a protein that pumps materials
across membranes. In this case, it pumps some of the material in earwax across
membranes. The single base change of this SNP is in the region of the gene that
codes for the protein and causes an amino acid change from glycine to arginine. Can
changing just one amino acid have a dramatic effect on a protein's function? Do you
think changing any one amino acid would necessarily have a big effect? Explain why
you conclude this.
17. If the whole ABCC11 protein is 1380 amino acids, at least how long must the mRNA
be? (Show your calculations.)
The SNP is at base 538 of the mRNA. At this site the sequence is either a G or an A on
the coding strand but the 23andMe site shows the SNP as a C or T because 23andMe
reports the sequence of the complementary strand.
18. Look at the genetic code on the last page of this handout. Could a single G to A
change cause a change from Glycine (abbreviated Gly or G) to Arginine (Arg or R)?
Which base of the codon must this be?
IV. Taste Blindness! It probably is not surprising that we differ in our ability to taste.
These differences are probably a big part of why we like different foods. Take a look at the
Traits list and find “Bitter Taste Perception”.
19. What does the gene code for?
20. If individuals have two of the bad alleles they have an 80% chance of not tasting
bitterness. Considering what the gene codes for can you propose an explanation for
why we have to have two bad copies of this gene to not be able to taste?
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21. Would Mendel consider the allele that allows one to taste bitter compounds to be a
dominant allele?
22. What is a possible evolutionary advantage of being able to taste bitter compounds?
23. (Optional) If you want to learn more read, on in the section below: Learn More
About TAS2R38. Here are a couple of questions to think about from that section:
a. Might there be an advantage to having the taste-blind allele?
b. What might be the advantage of having the taste-blind allele and the normal
allele?
V. Freckles: Let's take a look at a bit of the biology behind freckling.
Go to “Freckling” under “Traits” in the “My Results” section.
24. How many different genes do they examine for this trait?
25. Does any one of these genes control this trait completely?
26. The two traits we looked at above (earwax type and taste-blindness) are largely
determined by genetics. Many traits are affected by the environment and not just
determined by genetics. Do you think freckles may have a big contribution from the
environment also?
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VI. Farts...oops, safety! Do you like ice cream...but does it not like you? Many people are
not able to digest lactose. Take a look at the page on lactose intolerance under “Traits” in
the “My Results” section.
This is an interesting example that adds some new twists.
27. What enzyme do we all produce as babies to digest lactose? (About 40% of the
total calories in breast milk is from lactose.)
28. People who can digest lactose as adults continue to produce this enzyme. The
ability to produce the enzyme is determined by genetics. Look at the panel
"Understanding your Results". How can the environment affect this phenotype?
29. In the previous examples some of the SNPs were in the coding regions of genes. The
SNPs identified here aren't in the coding region, but are near by. How can mutations
near a gene affect whether or not the protein is made.
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VII. Don’t Give Me a Heart Attack!
30. Do you think that there is an environmental component to heart disease? If yes,
what are some examples of how the environment or behavior can affect heart
disease?
31. Do you think that your genes have an effect on the chance you will develop heart
disease?
32. Open up “Click on Results”, then “Health Risks”, and the “Coronary Heart Disease”.
Compare the results for Greg Mendel and for Lily Mendel. Is there a genetic
component?
33. Look in Understanding your Results on the same webpage to see the genetic
contribution along with a list of the environmental factors that can have an affect
heart disease.
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34. Scroll down to the “Marker Effects” graph. What do each of the bars and their color
and height represent?
VII. What is a Phenotype?
OK, we’ve been looking at genes and some to the SNPs in them. Our DNA sequence is our
genotype. What is our phenotype? Let’s check out another video:
https://www.23andme.com/gen101/
35. So, what is a phenotype?
36. Is your phenotype determined only by your genotype? (Think back to the
examples we have seen above.) Were some of the phenotypes we looked at above
controlled more by your genes than others?
VIII. Ancestry…where did I come from?
Let’s take a look at 23andme’s video: “Where do your genes come from?”
https://www.23andme.com/gen101/origins/
37. Why do we have two copies of most chromosomes?
38. What are matching pairs of chromosomes called?
39. What is different about X and Y chromosomes?
40. What are mitochondria? Did you know if they have DNA also?
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41. Why would mitochondria have DNA? (This isn’t in the video!!)
We inherit our mitochondria from our mother so we can use it to trace our maternal lineage
by comparing SNPs between mitochondrial sequences. Go back to the sample genotypes of
the Mendels at 23andme. Click on “My Results” and then “Maternal Line” to see the
Mendel’s mitochondrial type (or haplotype).
Explore the links here.
42. What percentage of their genes are of Neanderthal origin?
43. What is their most likely ancestry?
There are many interesting links at 23andMe:
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For a fun look at some other really interesting the links between genes and disease
click on "Discoveries" on the 23andMe homepage or go to:
https://www.23andme.com/about/factoids/
Under the “my results” section you’ll find tons of information on many different
traits, diseases, responses to drugs and more.
Lots more good stuff if you look around their site.
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The Genetic Code:
Image from: Godfrey-Smith, Peter and Sterelny, Kim, "Biological Information", The Stanford
Encyclopedia of Philosophy (Fall 2008 Edition), Edward N. Zalta (ed.), URL =
<http://plato.stanford.edu/archives/fall2008/entries/information-biological/>, accessed Feb. 27,
2012
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