How to be a Breast Cancer Detective

What is cancer?The common elements of manytypes of cancer are:1) Cancer cells grow without externalstimulation of growth factors.2) Cancer cells resist growth suppressionsignals from within and without.3) Cancer cells become immortal andoverride the features that normallylead to cell death.4) Cancer cells do not respect tissueboundaries, so they become invasiveand metastasize.

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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

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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

FF1

F2

F3

A special family

View film clip

• Mary Claire king: Finding brca1 and 2 by pedigree- http://www.dnai.org/media/a/king296 04.swf

Draw your own pedigree chart

1. Go back 3 generations in a family2. Let circles = females3. Let squares = males4. Half shaded = has unexpressed trait5. Shaded area = has disease6. Shaded area with line drawn

through=died from disease

Finding the GenesWhat are genes?

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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.

View film clip

If a person inherits one of the mutationsassociated with cancer, he or she willhave a higher risk of developing thatcancer than people who have a healthyversion of that gene.Mark Skolnick: Finding the breast cancer

gene brca1: www.dnai.org/media/a/skolnick298_06.swf

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 immune-

system 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 Box4. 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 2Examine 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-delta9-10-11b, 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