Download Slide 1 - Inside Cancer

How to be a Breast Cancer
Detective
What is cancer?
The common elements of many
types of cancer are:
1) Cancer cells grow without external
stimulation of growth factors.
2) Cancer cells resist growth suppression
signals from within and without.
3) Cancer cells become immortal and
override the features that normally
lead to cell death.
4) Cancer cells do not respect tissue
boundaries, so they become invasive
and metastasize.
www.breastdoc.com/.../Genetic-2.jpg
Only 5-10 % of breast and ovarian
cancer is inherited.
If either one of your parents carry the gene, there
is a 50% chance of inheriting the mutation
regardless of the child's sex
www.breastdoc.com/.../Genetic-2.jpg
When studying human genetic diseases, geneticists often
use pedigree charts to represent the inheritance of traits.
How many individuals have died or are affected by this
disease?
F1
F2
F
F
1
F3
A special family
View film clip
• Mary Claire king: Finding brca1 and 2 by
pedigreehttp://www.dnai.org/media/a/king29604.swf
Draw your own pedigree chart
1.
2.
3.
4.
5.
6.
Go back 3 generations in a family
Let circles = females
Let squares = males
Half shaded = has unexpressed trait
Shaded area = has disease
Shaded area with line drawn
through=died from disease
Finding the Genes
What are genes?
www.breastdoc.com/.../Genetic-2.jpg
We all have the BRCA 1 and 2 genes, which are located
on chromosome 13 and 17, respectively. A mutation in the form of
extra DNA or loss of DNA that occurs in the gene is a problem.
If a person inherits one of the mutations
associated with cancer, he or she will
have a higher risk of developing that
cancer than people who have a healthy
version of that gene.
Mark Skolnick: Finding the breast cancer
gene brca1:
www.dnai.org/media/a/skolnick298_06.swf
View film clip
Why use Bioinformatics?
Bioinformatics and combinatorial chemistry allow scientists
to sort through molecules (both natural and synthetic)
that interfere with cancer’s progress in a variety of ways.
In addition, the ability to measure many different
constituents (such as the DNA, RNA, and proteins) in
both normal cells and cancer cells, will enable a more
systemic genetic classification of cancer. Bioinformatics
can discern patterns in those measurements to help
better understand how cancer cells behave and how
they react to different treatments. Bioinformatics is based
on the actual genetic code of an organisms which has
been sequenced using Biotechnology.
Uses of Biotechnology and
Bioinformatics
• the ability to create vaccines
• identification of protein markers for detecting
and diagnosing cancers
• purification of interleukin and other immunesystem enhancers
• the preparation of bone marrow cells for
transplants
• the manipulation of natural products like taxol
(from the Pacific yew tree) to make improved
compounds that interfere with cell division
Let’s do Bioinformatics-finding the
breast cancer gene
1. Google “NBCI”.
2. Choose first hit.
3. Type in Brca 1 in Search Box
4. Choose a nucleotide in left box.
5. Click “Go”
6. You will now be presented with a long page of
gene choices. See if you can identify some of
them by their Latin names.
7. Click on a Brca 1 sequence and open it.
There is a lot of information here.
Step 1 –Google NCBI
• NCBI HomePage
• The National Center for Biotechnology
Information (NCBI) provides an
integrated approach to the use of gene
and protein sequence information, the
scientific literature (MEDLINE ...
• www.ncbi.nlm.nih.gov
Step 2
Examine a breast cancer variant
genome:
LOCUS NM_007305 3759 bp mRNA linear
PRI 28-JUL-2008 DEFINITION Homo
sapiens breast cancer 1, early onset
(BRCA1), transcript variant BRCA1-delta910-11b, mRNA.
Questions
1. What is a “locus”?
2. How many “bp” base pairs are found in
this locus?
3. Where is the gene found?
4. What does the gene encode for?
Finding the coding sequence
CDS
• The CDS codes for a functional protein.
• Find the CDS of this gene by scrolling
down to CDS. Next to this you will find a
locus: 201…..2360.
• Carefully highlight, cut, and paste the
nucleotides from 201 to 2360 onto a word
document.
• Save it under “CDS-breast cancer gene”.
Finding similar Coding Sequences
for functional genes
• Its fun and interesting to find the same
CDS in other animals, especially ones
which are available to researchers.
• One such animal is the C. Elegans, a
nematode worm about 1 mm in length.
• How can we find organisms with similar
sequences?
BLAST
• One way is to use a bioinformatics
program called BLAST.
• It takes a sequence and searches for
similar ones in its database.
Directions for a Nucleotide BLAST
•
•
•
•
Go back to the NCBI homepage
Click Blast
Mark “nucleotide” BLAST
Copy and paste your nucleotide CDS into
BLAST
• Next to database : click others
• Optimize for somewhat similar sequences
• Click BLAST button
What are your results?
Find the % similarity of the gene in the:
• Chimpanzee
________%
• Gorilla
________%
• Mouse
________%
• Rat
________%
Summary
1. Cancer is a disease caused by……..
2. What percentage of breast cancers are caused
by mutations?
3. What is the name of the gene responsible?
4. If one of your parents have the gene, what are
your chances for having the gene?
5. How do scientists study family inheritance?
6. How has Biotechnology helped us solve
the cancer problem?
7. Why does Biotechnology rely on
Bioinformatics?
8. What type of information can a
Biotechnology website give us?
9. How can we apply what we have found it
today to a future research project?
Final Video Clip
Mary Claire king: Can women be tested for
breast cancer?
http://www.dnaiorg/media/a/king295_08.swf