Download Genetics: Smoking out BRCA2

Biology
Genetics:
Smoking out BRCA2
Doctors have known for years that smoking causes lung cancer, but
scientists have recently stumbled on to a specific genetic "spelling error"
– in a gene already famous for causing breast cancer – that adds to the risk
of developing the disease.
In this lesson you will investigate the following:
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What are bases and how do they help make you, you?
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When are mutations harmful?
•
What is bioinformatics?
Are you ready to untangle your understanding of DNA, genes and
chromosomes?
This is a print version of an interactive online lesson.
To sign up for the real thing or for curriculum details about the lesson
go to http://www.cosmosforschools.com
Introduction: Genetics
When you're tuning a guitar, the smallest of tweaks can make a big difference to the way the instrument sounds. And in
books, small changes in the way the words are put together can change how the story unfolds – little changes can have big effects.
The same applies to DNA – the molecule that carries the genetic information you inherited from your parents. Your DNA directly
affects how your body is built and functions, and small changes in the information it contains – mutations – can have a big impact.
Often these mutations occur because the processes used to copy DNA are imperfect. Very occasionally the misspellings originate in
your own body, but most often they are inherited from parents, who in turn likely inherited them from their parents. The mutations
can alter the construction of proteins vital to our bodies, with significant harmful results. On the other hand, many mutations have
no noticeable effects at all.
BRCA2 is a very well studied gene because it has a mutation that increases a woman's chance of breast cancer five to ten times. In
fact, the gene's name stands for Breast Cancer 2. But recently scientists found a new mutation on the same gene. It also increases
the risk of breast cancer but is dangerous in a different way as well – it significantly increases the risk of lung cancer in smokers.
Which goes to show how two small tweaks in the same gene can carry two very different – and dangerous – tunes.
Read the full Cosmos Magazine article here.
Children often look similar to their parents with family resemblances that can run for generations.
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Just to warm you up, here are some questions to find out what you already know about genes. Perhaps you can discuss them in
class before answering.
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Question 1
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Question 2
If you look more like one parent then you have inherited more
Boys get all their traits from their fathers and girls get their
of that parent’s genes.
traits from their mothers.
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True
True
False
False
Question 3
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The genetic information passed on to you from your parents
came from their sex cells – that is, from your father's sperm and
your mother's egg cells.
Question 4
Your genes determine all your characteristics.
True
False
True
False
To finish the section, a quick poll to check your understanding...
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Poll 1
A mutation to any part of your DNA is:
 This poll is currently closed, so you can't vote
always harmful
sometimes harmful and sometimes harmless
always harmless
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Gather: Genetics
Left: DNA samples are often taken by lightly scraping the inside of the mouth. Some of our cells, containing DNA, are in
the saliva. Right: Testing DNA in a lab.
DNA, chromosomes and genes
Gregor Mendel showed in 1865 that both parents pass traits on to offspring. But no-one knew how. It wasn’t until 1944 that the
chemical substance that carried these traits was discovered. It was a molecule called deoxyribonucleic acid, or DNA.
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Question 1
Match: Which of the following statements apply best to DNA, gene or chromosome.
Statement
Shaped like a twisted ladder called a double helix
Contains many genes
Unit of instruction inherited from parents
Constructed from sugar and phosphate molecules and four bases
Long DNA molecule packaged tightly into a coil
Provides a particular cellular instruction (to make a protein)
Each DNA molecule is a double helix. You can easily see the two
strands in the diagram (right) where the double comes from, and
helix just means that the strands are twisted around each other.
If you straighten out the molecule, DNA looks like a ladder. Each
"step" is made up of two bases – also called nucleobases. These
link together, joining the two strands of the molecule together.
There are four types of base and each one links to only one
other type, forming base pairs:
adenine (A) and thymine (T) link together – A-T
guanine (G) and cytosine (C) link together – G-C
When all the bases on two DNA strands align in their A-T and GC pairings a stable DNA molecule forms.
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applies to...
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Question 2
Label: In the sketchpad below:
1. Drag the text to correctly label the diagram.
2. Drag and position the coloured bases to fill in the gaps in the DNA strands. You will need to rotate some of them.
se File
Did you know?
In humans, each DNA molecule is from 3.5 cm to 5 cm long. Put
all the DNA from the 46 chromosomes – in just one cell – end-toend, and it comes to 1.8 m. That's probably taller than you! Sometimes, for example when a cell is dividing, the DNA
molecules coil themselves up to form the Hshaped chromosomes you sometimes see pictures of. They end
up about 2.5 µm long – 1/16,000th of their original length.
Codons, amino acids and proteins
The sequence of bases in each gene provides instructions for building proteins.
Proteins are molecules. They are often very large, made up of many thousands of atoms, and they are critical to all living
organisms. They make up most of the tissue in the organisms' bodies and help control all of the chemical reactions that occur in the
organisms. 5
When the machinery in a cell reads the bases that make up a gene it interprets them in groups of three. Each group of three
is called a codon. Codons "code" for amino acids – the building blocks of proteins.
So, to summarize:
genes are made up of sequences of bases,
bases are grouped into codons,
codons code for amino acids,
amino acids make up proteins.
With the essential roles that proteins play, you can see how important our genes are!
Mathematical interlude
There are 4 bases – adenine, thymine, guanine and cytosine – and 3 each of these per codon. All possible codon permutations
occur in nature, for example, ATG, GTA, TTT, and so on. How many are there in total?
To answer this we'll start with a simpler example...
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Question 3
List: Let's begin with just 3 letters (a, b, c) and 2 positions. How many permutations does this give?
One way to answer is to write down every permutation and then count them. Do that below – write down all the possible
permutations of 3 letters with 2 positions, and then count how many permutations there are.
Hint: One way to be sure you get every permutation is to start by putting the first letter in the first position and then going through all the
possible letters in the second position – aa, ab, ac. Then move to the second letter in the first position and again go through all the
possibilities for the second position. And so on.
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Question 4
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Question 5
Deduce: Listing all the permutations gets harder if you add
Calculate: Returning to the original question, how many
more letters and positions, but you can use a formula instead. codon permutations are there? In this case:
One of the formulas below is the correct one for working out
the total number of letters (L) = 4 (the 4 bases)
the number of permutations (P). Use your answer from the last
question to choose which one. Remember, for that example:
the number of positions (S) = 3 (3 bases per codon)
the total number of letters (L) = 3
the number of positions (S) = 2
P = S × L
P = L
S
P = S + L
P = S
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L
Using the formula you selected in the previous question,
calculate the number of permutations.
End of the mathematical interlude
Human proteins are made from 20 amino acids. Your answer above should have told you that there are more codon
permutations than that, so some amino acids are coded for by more than one codon. Which codons code for which amino acids can be shown in a codon wheel, like the one below.
To use it, find the first letter of your codon in the inner circle and work outwards to the second letter and finally to the third letter.
The outermost ring shows the amino acid coded for. Hint: To double-check your answer for the number of codon permutations above, you can count the number of sections in the third ring of
the codon wheel.
Here are some examples using the wheel: 1. ATG = methionine – this amino acid is found at the start of every gene
2. GTA = valine
3. TGA, TAA and TAG do not code for amino acids. They each stop protein creation.
Note: You can download a PDF of the codon wheel below to print.
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codon_wheel_A4_.pdf
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Question 6
Identify: Identify one amino acid that is coded for by more than one codon. Write two 3-letter codon sequences associated with
your chosen amino acid.
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Question 7
Interpret: In the sketchpad below:
1. Use the codon wheel to find the amino acids that the bases code for (the first one is done for you).
2. Drag the text labels to their correct positions.
se File
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Question 8
Determine: Two of the following DNA sequences code for the same small protein. Determine the amino acid sequence of that
protein.
1. ATG TTA ACG AGA AGT
2. ATG CTA AGG AGT TCG
3. ATG CTC ACT CGT AGC
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Process: Genetics
Left: People with Marfan syndrome are very often tall with long, thin arms, legs and fingers. The condition is caused by a
single point mutation to the FBN1 gene. Right: Distichiasis causes people to grow additional eyelashes. It is caused by a
point mutation in the FOXC2 gene.
Point mutations
The Introduction tells how small changes in genes can have big consequences. Scientists use the term mutation to refer to any
such changes that persist, passing down to new generations. There are many different types of mutations, but some involve a
change to just a single base. These are called point mutations.
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Question 1
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Define: A point mutation is a change in a single
Question 2
Consider: If a point mutation causes a frameshift, the resulting
protein is likely nonfunctional. This is because:
amino acid
frameshifts only change a single amino acid, but
base
that is enough to disable the resulting protein.
gene
frameshifts always replace many bases, changing
protein
the sequence of amino acids in the protein.
all the amino acids after the changed base are
likely to be different.
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Question 3
Identify: The sketchpad below has an original base sequence and three mutations of it, each one caused by a different point
mutation.
1. Drag the text to the appropriate text boxes to identify and explain each type of point mutation.
2. Drag the arrows to show which base changed in each mutation, or where a base was removed.
se File
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Question 4
Deduce: The sketchpad below has the same original sequence and point mutations as the question above. This time:
1. Use the codon wheel to work out the amino acids produced in each case, and write them in.
2. Put ticks or crosses in the appropriate boxes to indicate if the point mutations have changed the amino acid sequences, and if
there has been a frameshift.
se File
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Question 5
Summarize: For each of the two point mutations below:
Drag an arrow to identify where the mutation occurred
Use the DNA codon wheel to find the mutated sequence
Name the type of point mutation
se File
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Question 6
Reason: A single-base substitution can occur in the first, second or third position of a codon. In which position is the point mutation
most likely to go unnoticed?
Why? Use examples from the DNA codon wheel to support your answer.
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Haemochromatosis
Haemochromatosis, or inherited iron overload, is a treatable metabolic disorder caused by DNA mutations. 1:25
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Question 7
Relate: People faced with haemochromatosis, either because they have or carry the condition or someone in their family does, can
meet with a genetic counsellor to discuss the disorder and seek advice. You can find some of the information they might be given in
this booklet. Working with a partner, jot down three or four questions that someone with haemochromatosis in their family might want to ask,
and the answers. Work these into a short dialogue between the person and a counsellor.
Act out your dialogue in front of your class peers. If you have time, switch roles.
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Apply: Genetics
Project: Bioinformatics investigation or haemochromatosis
presentation
Scientists now have powerful technologies for reading the bases in your DNA.
For this Apply you have a choice – you can:
investigate an online bioinformatics database, or
create a presentation to explain the haemochromatosis point mutation.
If you have time, do both!
Bioinformatics investigation
Background
You may have seen the movie “GATTACA”. Set in the future, a character provides a hair sample and receives a complete DNA
analysis in a matter of minutes. In reality, no machines can do this yet, but there is steady progress. Since 2003 when the entire human genetic sequence – the
human genome – was first determined, DNA sequencing technologies have been getting cheaper and faster.
But even once all of your A’s, T’s, C’s and G’s are known it is not possible to simply look at the data and know what proteins or
characteristics it codes for – that is far more complex. To help sort out those questions scientists use enormous databases and the
techniques of bioinformatics.
The National Center for Biotechnology Information (NCBI) houses a collection of more than 40 bioinformatics databases, all
freely available to scientists and the public. 14
Aim
The aim of this task is to locate information about the human BRCA2 gene and in so doing show the extensive range of information
in the NCBI databases.
Hint: If you have a computer or laptop, open two browser windows so you can keep the instructions below open alongside the NCBI site. If
you are on a tablet it could be helpful to use two devices, e.g. your phone and the tablet.
Gene search
1. Open the NCBI homepage here.
2. In the search fields at the top of the page:
a. select Gene in the left field,
b. type “BRCA2[SYMBOL]” into the text search field, and
c. click Search.
Results from the search are presented in a table.
Note that the second column has a brief
description of the gene and identifies the organisms
in which is has been found. Column 3 indicates which
chromosome the gene is found on.
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Question 1
Identify: Name four organisms that have the BRCA2 gene. 
Question 2
Observe: Is the BRCA2 gene found on the same number
chromosome in each of these organisms?
No
Yes
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Question 3
Consider: Why do you think scientists are interested in studying the BRCA2 gene in organisms other than humans?
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Map viewer​
1. The NCBI site has a tool called the Map Viewer, for
browsing the genetic sequences of organisms. Click here
to open it.
The home page opens with the sequence
Vertebrates/Mammals/Primates expanded.
2. Find the row for Homo sapiens and click on the latest
Annotation Release.
You see representations of all the human
chromosomes. Most are numbered, but three are not. The
abbreviations “X” and “Y” refer to the sex chromosomes.
“MT” is for the DNA in human mitochondria – our cell
nuclei are not the only place we have DNA.
3. Click on the number under chromosome 6.
On the left is a diagram of the chromosome, and some of
the genes on it are listed down the middle of the
page under the heading Symbol. Can you see HFE, the
haemochromatosis gene? Scroll to the bottom of the page. How many genes are
there on chromosome 6? (Answer below).
4. Go back to the previous page and now open chromosome
13.
Can you see BRCA2 listed?
Scroll to the bottom of the page. How many genes are
there on chromosome 13? (Answer below).
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Question 4
Research: How many genes are there on chromosome 6?
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Question 5
Research: How many genes are there on chromosome 13?
Full description of human BRCA2 gene
Still in the Map Viewer with chromosome 13 open, click on the
link for the BRCA2 gene.
A full description of the human BRCA2 gene opens.
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Question 6
What is the official full name for the BRCA2 gene?
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Question 7
Complete: Use the information in the Summary to complete
the following statement:
Inherited _______ in BRCA1 and this gene, BRCA2, confer
_______ lifetime risk of developing _______ or ovarian _______.
Base sequence of BRCA2
1. Click NCBI Reference Sequences (RefSeq) in the Table of
Contents on the right side of the page.
This takes you down the page where you should see a
small section labelled Genomic.
2. In the Download row of the Genomic section click
GenBank.
The page that opens shows DNA information about BRCA2.
3. Scroll down the page to a section titled ORIGIN, and then
scroll through this. This is all the bases that make up the
gene. How would you like to decode all those codons!?
4. How many bases are there in the gene? (Answer below. In
order to answer there is a count row beside the ORIGIN
list, but the answer is also given in the first line of the page,
as "bp" for "base pairs".)
5. Usually, not all the codons in a gene are translated into
amino acids. What is the maximum number of amino acids
that the BRCA2 gene could code for? (Answer below).
6. Scroll to roughly half way between the top of the page and
the ORIGIN section, to a section labelled /translation.
This list of letters is the amino acids that make up the
BRCA2 protein. There are 3,418.
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Question 8
Extract: How many bases are there in the BRCA2 gene? What is
the maximum number of amino acids these could code for?
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Question 9
Observe: What is the first amino acid in the gene? Why should
this not be a surprise?
Haemochromatosis presentation
You are a specialist in genetics. A colleague from your research institute was invited to explain haemochromatosis to interested
members of the public, but she has come down with a severe cold and can't attend. She has asked you to do the presentation for
her.
She jotted down some of the main points she wanted to cover but, although she says they are fairly complete, they are still jumbled
up in the order that she thought of them. As well, she has made a start on slides for a presentation, with some images and text
ready.
1. In the sketchpad below, organize the images and text your colleague prepared on the slides in the order you want to present
the material. You can add or edit labels if you want.
2. In the text question that follows, write what you will say as you present each slide.
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Your colleague's notes
HFE protein sits in cell membrane, helps control the flow of iron into the cell
Haemochromatosis due to point mutation on gene HFE
mutant HFE protein lets too much iron into the cell
early symptoms: tiredness, joint pain, stomach pain
TGC codon mutated to TAC
later symptoms: liver disease, irregular heart beat, arthritis, diabetes (affects the pancreas)
HFE protein has 348 amino acids – mutation affects no. 282
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Question 10
se File
Present: Now it's over to you. You have to make this presentation your own so you you will probably want to add some of your
own text and maybe some arrows. If you have the time you could even draw diagrams or find new images to add, though your
colleague says that there should be enough with what she has prepared. The meeting organizer says you can use up to 6 slides.
Hint: You can resize any of the images if you need.
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Question 11
Speak: Write down what you will say for each of the slides in your presentation.
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Career: Genetics
2:50
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Question 1
Relate: ​
Nancy's role requires a) a strong understanding of her area of science, b) an ability to "translate" the science so that
members of the public can understand it, and c) the ability to provide emotional support to people faced with serious illness. For each of these three elements of the job name one personal quality that would help someone carry out this part of the role. Do you think you have any of these qualities? Would you want a career where you would exercise one or more of them? If so,
explain what qualities and what sort of job. If not, what qualities do you have that you would like to take advantage of in your
career? Cosmos Lessons team
Lesson author: Hayley Bridgwood
Profile author: Megan Toomey
Editor: Jim Rountree
Art director: Wendy Johns
Education director: Daniel Pikler
​
Image credits: iStock Photos, Timothy D. Joyce/National Marfan
Foundation, Reddit, DNA codon wheel, Genome Research
Limited
Video credits: Genome BC, Teachers Pet,
HaemochromatosisAust, NWHospital, YouTube
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