How to be a Breast Cancer Detective.
From Inside Cancer Wiki
How to be a Breast Cancer Detective.
Lesson Overview
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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 an individual. 5) learn bioinformatics techniques of searching for specific genes in databases. 6) learning how to read a bioinformatics gene page 7) finding similar coding sequence regions in other organisms
Common Misconceptions
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The Lesson
Preparation Before class: (materials, handouts etc.) Part 1. 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 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
Part 2: Discussion of Biotechnology and bioinformatics based on reading Image:Biotechnology.doc
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)
Finding the Brca 1 gene using bioinformatics
Time required
Part 1- 45 minutes Part 2 -2 45 minute periods
Student Handouts for the Lesson Plan
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Alternative Assessments
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Suggestions for Extended Learning
• Webster K Cavenee and Raymond L. White, “The Genetic Basis of Cancer,” Scientific American, March 1995. • Robert Cooke, Dr. Folkman’s War: Angiogenesis and the Struggle to Defeat Cancer • Jerome Groopman, “The Thirty Years’ War,” The New Yorker (June 4, 2001) • Matt Ridley, Chapter 17 in Genome: Autobiography of a Species in 23 Chapters • Robert Weinberg, One Renegade Cell • Lisa Yount, Cancer • 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- NCBI-National Center for Biotechnology Information Biotechnology-the scientific manipulation of living organisms, especially at the molecular genetic level, to produce useful products
Education Standards
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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
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
