How to be a Breast Cancer Detective.

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How to be a Breast Cancer Detective.

Lesson Overview

Briefly describe the lesson here.

The lesson begins with interpreting familial pedigree charts and continues with steps in the identification of the genes responsible for some breast cancers. It continues with searching for the BRCA1 gene and analysis and identification of the coding sequences through bioinformatics techniques.

Goals and Objectives

1) understand the process by which genes of parents are transferred to their offspring.

2) understand the difference between a dominant and recessive trait and understand how the presence of a trait may effect the physical characteristics of an individual.

3) read and/or construct a pedigree chart mapping a specific trait in a family.

4) determine the probability of a certain phenotype being expressed in a pedigree chart

5) Understand the uses of Biotechnology and Bioinformatics in understanding cancer

6) Learn to retrieve information from a Bioinformatics source.

Common Misconceptions

Students may not understand the importance and relevance of molecular 

genetics to research on today's world. Many students are not aware of the world of Bioinformatics.

The Lesson

Preparation Before class

Part 1. PowerPoint to accompany lesson, Introduction to Pedigree charts (handout),Highlighters, pens, pencils, books, chalkboard, and 1 computer with LCD projector and sound system

Part 2: Computer classroom; one computer per student, LCD projector,sound system

During class

Time required

Part 1- 45 minutes Part 1: Predicting the Breast cancer gene through Pedigree charts

       Practice drawing a pedigree chart
       

Begin by using PowerPoint presentation which contains links to other resources listed below:

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

Mark Skolnick: Finding the breast cancer gene brca1-http://www.dnai.org/media/a/skolnick298_06.swf

Mary Claire king: Can women be tested for breast cancer? http://www.dnaiorg/media/a/king295_08.swf

Time required

Part 2 -2 45 minute periods

How do mutations form? View film clip http://www.insidecancer.org/?s=A,1,7

1. Reading and Discussion of Biotechnology and Bioinformatics based on the reading below:

      Biotechnology’s Relation to Cancer Research 

Biotechnology has applied many of the techniques of cell biology, molecular biology, and protein chemistry to cancer research and treatment over the years. These developments include:the ability to create vaccines; the identification of protein markers for detecting and diagnosing cancers; the 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. New diagnostic abilities and drugs will result from related advances in genomics, proteomics, computer modeling, and bioinformatics. Genomics (the study of the genes on the chromosomes) is showing the exact chromosomal defect involved in cancers and pinpointing how key genes malfunction. Proteomics (the study of the proteins made by the genes) will define the function of the protein made by the defective genes in the cascade of cancer events. Computer modeling allows proteins to be considered in a variety of new lights, including indentifying potential docking clefts for the introduction of small molecules or proteins that might interfere with cancer causing protein functions. 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. (from Biotechnology and You,vol.11,issue 1)

2. Finding the Brca 1 gene using bioinformatics

Student Handouts for the Lesson Plan

Instruction sheet on steps in finding genes and using the NCBI website

Alternative Assessments

Poster of Breast Cancer Pedigree with correct key

Bioinformatics project using tools and websites found in this lesson.

Suggestions for Extended Learning

• Webster K Cavenee and Raymond L. White, “The Genetic Basis of Cancer,” Scientific American, March 1995.

• Matt Ridley, Chapter 17 in Genome: Autobiography of a Species in 23 Chapters

• Robert Weinberg, One Renegade Cell

• Time and Newsweek cover articles on cancer topics

• American Cancer Society: http://www.cancer.org

• National Cancer Institute: http://www.nci.nih.gov

• National Childhood Cancer Foundation: http://www.nccf.org

• Oncolink: http://www.oncolink.upenn.edu

• NOVA’s program on Judah Folkman, Cancer Warrior: http://pbs.org/wgbh/ nova/cancer

Glossary

Allele—an alternate form of a gene.

Chromosome—structure in the cell nucleus that stores and transmits genetic information.

Gene—unit of heredity.

Genotype—Allelic status of an organism for a genetic trait.

Heterozygous—having different alleles of a gene.

Homozygous—having indistinguishable alleles of a gene.

Pedigree—diagram showing the expression of a specific characteristic and the biological relationships among members of a family, often of several generations.

Phenotype—the observable organism, the expression of a genetic trait.

Bioinformatics- the science of using databases to enter or research genetic information on the WWW.

NCBI-National Center for Biotechnology Information

Biotechnology-the scientific manipulation of living organisms, especially at the molecular genetic level, to produce useful products.

CDS-Coding sequence

Education Standards

• Living systems also have different levels of organization--for example, cells, tissues, organs, organisms, populations, and communities. Within these systems, interactions between components occur. Further, systems at different levels of organization can manifest different properties and functions.

• Models are tentative schemes or structures that correspond to real objects, events, or classes of events, and that have explanatory power. Models help scientists and engineers understand how things work. Models take many forms, including physical objects, plans, mental constructs, mathematical equations, and computer simulations.

• Cells have particular structures that underlie their functions. Every cell is surrounded by a membrane that separates it from the outside world. Inside the cell is a concentrated mixture of thousands of different molecules which form a variety of specialized structures that carry out such cell functions as energy production, transport of molecules, waste disposal, synthesis of new molecules, and the storage of genetic material.

• Cells store and use information to guide their functions. The genetic information stored in DNA is used to direct the synthesis of the thousands of proteins that each cell requires.

• In all organisms, the instructions for specifying the characteristics of the organism are carried in DNA, a large polymer formed from subunits of four kinds (A, G, C, and T). The chemical and structural properties of DNA explain how the genetic information that underlies heredity is both encoded in genes (as a string of molecular "letters") and replicated (by a templating mechanism). Each DNA molecule in a cell forms a single chromosome.

• Recognize and analyze alternative explanations and models, reviewing current scientific understanding.

Teacher Answer Key

Part 2: Bioinformatics Brca 1 gene:

Questions

1.What is a locus? A position in the genome where a particular gene is found

2.How many “bp” base pairs are found in this locus? 3759 base pairs

3.Where is the gene found? mRNA Homo Sapiens

4.What does the gene encode for?

           This gene encodes a nuclear phosphoprotein that plays a
           role in maintaining genomic stability and acts as a tumor
           suppressor. The encoded protein combines with other tumor
           suppressors, DNA damage sensors, and signal transducers to form a
           large multi-subunit protein complex known as BASC for
           BRCA1-associated genome surveillance complex. This gene product
           associates with RNA polymerase II, and through the C-terminal
           domain, also interacts with histone deacetylase complex. This
           protein thus plays a role in transcription, DNA repair of
           double-stranded breaks, and recombination. Mutations in this gene
           are responsible for approximately 40% of inherited breast cancers
           and more than 80% of inherited breast and ovarian cancers.
           Alternative splicing plays a role in modulating the subcellular
           localization and physiological function of this gene. Many
           alternatively spliced transcript variants have been described for
           this gene but only some have had their full-length natures
           identified.

CDS of Human Breast cancer gene

                                tggatttat ctgctcttcg cgttgaagaa gtacaaaatg
     241 tcattaatgc tatgcagaaa atcttagagt gtcccatctg tctggagttg atcaaggaac
     301 ctgtctccac aaagtgtgac cacatatttt gcaaattttg catgctgaaa cttctcaacc
     361 agaagaaagg gccttcacag tgtcctttat gtaagaatga tataaccaaa aggagcctac
     421 aagaaagtac gagatttagt caacttgttg aagagctatt gaaaatcatt tgtgcttttc
     481 agcttgacac aggtttggag tatgcaaaca gctataattt tgcaaaaaag gaaaataact
     541 ctcctgaaca tctaaaagat gaagtttcta tcatccaaag tatgggctac agaaaccgtg
     601 ccaaaagact tctacagagt gaacccgaaa atccttcctt gcaggaaacc agtctcagtg
     661 tccaactctc taaccttgga actgtgagaa ctctgaggac aaagcagcgg atacaacctc
     721 aaaagacgtc tgtctacatt gaattggctg cttgtgaatt ttctgagacg gatgtaacaa
     781 atactgaaca tcatcaaccc agtaataatg atttgaacac cactgagaag cgtgcagctg
     841 agaggcatcc agaaaagtat cagggtgaag cagcatctgg gtgtgagagt gaaacaagcg
     901 tctctgaaga ctgctcaggg ctatcctctc agagtgacat tttaaccact cagcagaggg
     961 ataccatgca acataacctg ataaagctcc agcaggaaat ggctgaacta gaagctgtgt
    1021 tagaacagca tgggagccag ccttctaaca gctacccttc catcataagt gactcttctg
    1081 cccttgagga cctgcgaaat ccagaacaaa gcacatcaga aaaagcagta ttaacttcac
    1141 agaaaagtag tgaataccct ataagccaga atccagaagg cctttctgct gacaagtttg
    1201 aggtgtctgc agatagttct accagtaaaa ataaagaacc aggagtggaa aggtcatccc
    1261 cttctaaatg cccatcatta gatgataggt ggtacatgca cagttgctct gggagtcttc
    1321 agaatagaaa ctacccatct caagaggagc tcattaaggt tgttgatgtg gaggagcaac
    1381 agctggaaga gtctgggcca cacgatttga cggaaacatc ttacttgcca aggcaagatc
    1441 tagagggaac cccttacctg gaatctggaa tcagcctctt ctctgatgac cctgaatctg
    1501 atccttctga agacagagcc ccagagtcag ctcgtgttgg caacatacca tcttcaacct
    1561 ctgcattgaa agttccccaa ttgaaagttg cagaatctgc ccagagtcca gctgctgctc
    1621 atactactga tactgctggg tataatgcaa tggaagaaag tgtgagcagg gagaagccag
    1681 aattgacagc ttcaacagaa agggtcaaca aaagaatgtc catggtggtg tctggcctga
    1741 ccccagaaga atttatgctc gtgtacaagt ttgccagaaa acaccacatc actttaacta
    1801 atctaattac tgaagagact actcatgttg ttatgaaaac agatgctgag tttgtgtgtg
    1861 aacggacact gaaatatttt ctaggaattg cgggaggaaa atgggtagtt agctatttct
    1921 gggtgaccca gtctattaaa gaaagaaaaa tgctgaatga gcatgatttt gaagtcagag
    1981 gagatgtggt caatggaaga aaccaccaag gtccaaagcg agcaagagaa tcccaggaca
    2041 gaaagatctt cagggggcta gaaatctgtt gctatgggcc cttcaccaac atgcccacag
    2101 atcaactgga atggatggta cagctgtgtg gtgcttctgt ggtgaaggag ctttcatcat
    2161 tcacccttgg cacaggtgtc cacccaattg tggttgtgca gccagatgcc tggacagagg
    2221 acaatggctt ccatgcaatt gggcagatgt gtgaggcacc tgtggtgacc cgagagtggg
    2281 tgttggacag tgtagcactc taccagtgcc aggagctgga cacctacctg ataccccaga
    2341 tcccccacag ccactactga