No Growth Factor present (A) - - (B) - + (C) + - (D) + + (E) I don t know. With Growth Factor present

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1 Bio 111 andout for ancer I This handout contains: Today s ilicker Questions Useful web links for quitting smoking handout for this lecture Information for the final exam. ilicker Question #32A before lecture Which of the following statements are true? (A) ells can become cancerous because they have been infected by bacteria. (B) ells can become cancerous because mutations cause them to grow when they should not. () ells can become cancerous because mutations cause them not to grow at all. (D) All of the above. (E) ne of the above. ilicker Question #32B after lecture In the table below, means the cells grow under these conditions; means that they do not grow. Which row in the table corresponds to the phenotype of a cancer cell? With Growth Factor present Growth Factor present (A) (B) () (D) (E) I don t know. Useful Weblinks for Quitting Smoking Thanks to Danielle (111 Fall 2002) for suggesting that it is not enough to say, Smoking is really really bad for you. ere are some links with useful quitting information (recommended by a former smoker): Massachusetts Department of ealth: Smoking 12step programs: Another useful link: Let me know if you know of any more. ancer 11

2 Bio 111 Lung ancer Statistics Major types: (distinguished by where they form & what the tumor cells look like) Epidermoid carcinoma Adenocarcinoma Large ell arcinoma Small ell arcinoma The following data are from ancer: Principles & Practice of ncology DeVita, &al. they are from 1985, but little has changed since then (the 2001 average 5year survival is only 15%!) Epidermoid arcinoma Adenocarcinoma Large ell arcinoma Small ell arcinoma Incidence % of cases in Smokers year survival with treatment* % of all cases surviving % survival after surgery Top 5 metastatic sites lymph nodes thorax pleura liver adrenals lymph nodes pleura other lung adrenals NS lymph nodes pleura adrenals liver other lung lymph nodes liver adrenals pancreas bone pleura the membrane lining the lungs adrenals glands that secrete adrenaline (among other hormones) NS central nervous system (brain & spinal cord) pancreas gland that secretes digestive enzymes & insulin * Why so poor a prognosis? lung cancer is vigorous & highly metastatic By the time it s detected, the tumor has been growing for a long time: Typical symptoms that brought people to a doctor who then found out that they had lung cancer: persistent cough hemoptysis = coughing or spitting blood dyspnea = difficuty breathing, shortness of breath these would not appear until the tumor is welldeveloped making successful treatment less likely ancer 12

3 Bio 111: Information for Final Exam Basic Facts The exam will be held in Lipke and another room on {to be announced}. The exam will consist of approximately 5 questions; you should have plenty of time. roughly 25 points will be on ancer roughly 75 points will be on the whole course. These will not be multiple choice; they will be problemsolving. A typical problem starts with a simple question, and then gets harder. I have attached a modified version of the final exam from last year as a study guide. Since Lipke will be very crowded, I will hand out two different exams to prevent cheating. The two exams will contain virtuallyidentical problems; students sitting in adjacent seats will receive different exams. talking or communication of any kind between students is permitted once the exam begins. If you have a question, ask me or your TA. Anyone caught talking will be removed from the class. Genetics You need to know the overall processes of mitosis & meiosis how to solve problems involving: one gene two or more alleles sexlinked/autosomal traits probability & risk pedigrees how to draw chromosomes, genes, and alleles as on Exam 1 and also how to draw the DNA of chromosomes like I did in Molecular Biology 7. how bloodtype is inherited in humans You do not need to know: the details of mitosis & meiosis the details of any genetic disease or trait (except blood type) Biochemistry & ell Biology You need to know: how to draw a chemical structure that follows all the bonding rules how to look at a chemical structure and tell which parts are hydrophobic/hydrophilic (rank in order) what type of bonds each part can make (ionic, bond, phobic, & relative strengths) how to interpret & explain effects of amino acid changes ΔG, coupled reactions, rate, activation energy, catalysis ATP ADP P I ; which is high/low energy; what you can do with ATP You do not need to know: levels of protein structure & forces that govern their formation which bonds are polar or nonpolar. You will be given a copy (attached to the exam) of the Summary hart see the Lab Manual any specific chemical structures; you will be given (attached to the exam) a table of amino acid structures listed alphabetically with the exam (see the Lab Manual) any specific pathway or enzymatic reaction NAD/glycolysis/respiration/photosynthesis cell parts & the differences between plants/animals/prokaryotes ancer 13

4 Molecular Biology You need to know: DNA/RNA rules & Table of starts, stops, etc in Lab Manual Transcription & which strand is made Translation & start codon & stop codon & reading frame Mutations types from lecture & consequences Parts of a gene (differences between prokaryotic genes & eukaryotic genes) & how mutations in each of them could affect the protein being produced how to do problems that combine Genetics, Biochem, & Molecular Bio like those assigned in APAIB hapter 4. ribozymes and RNAi like in Exam III You do not need to know: hargaff s ratios (%A %G % %T) DNA/RNA structure DNA replication & leading & lagging strand the structures of the basepairs Enzymes & details of DNA replication trna & other details of translation the structure of any particular gene the experiments that showed that genes were made of DNA You will be given: a table of the genetic code. AIDS You need to know: the differences between a viral and a bacterial infection the general virus & IV life cycles how to explain the effect of an antiaids drug given how it works how IV leads to AIDS You do not need to know: the specific effects of any antiaids or antianthrax drug how infection by the anthrax bacterium leads to symptoms ancer You have to know: the general progression of cancer (normal, benign, malignant) & the changes at each level (loss of growth control, loss of adhesion) the pathway of growth control from lecture (receptor, ras, p53, etc) how mutagens lead to mutations (roughly, not the chemical details) You will have to be able to understand & explain: how mutations in the components (receptor, ras, etc) can lead to cancer why some cancercausing mutations have dominant or recessive phenotypes how mutations in certain genes can lead to increased cancer risk how a chemotheraputic drug acts against cancer, given how it works You do not have to know: cancer terminology & lung cancer statistics the steps that lead to any particular tumor the properties of any particular chemotheraputic drug You may bring in four sheets of (8 1/2 x 11 inch) paper with any notes you want. You may write on either or both sides of all the sheets. ancer 14

5 Bio 111 Fall 2006 final exam: Question 1: Genetics (20 points) You are studying a rare human genetic disease. A pedigree for a family with this disease is shown below: 1 2 Key: male Affected unaffected female a) Based on the pedigree above, what is the most likely mode of inheritance of this disease. ircle one: (4 pts) sexlinked recessive autosomal recessive autosomal dominant b) Based on your choice in part (i), define appropriate genotype symbols: (2 pts) allele contribution to phenotype) c) Using the symbols you defined in part (ii) give the genotypes of the following individuals: (2 pts each) #1 #2 #3 #4 #5 ancer 15

6 Question 1, continued: d) If individuals 3 and 4 have another child, what is the chance that that child will have the disease? (4 pts) chance that 3 & 4 s next child will be affected Justify your answer: You should not need to write below this line. ancer 16

7 Question 2: hemistry & Biochemistry (32 points) NTE TAT A TABLE F EMIAL PRPERTIES AN BE FUND N PAGE 11. a) In the space below, draw a molecule that has the formula 2 4 N 2 (that is, it is made of 2 carbons, 4 hydrogens, one nitrogen, two oxygens, and one atom has a negative charge). Be sure that: 1. your structure obeys the bonding rules 2. you show all the atoms 3. you show any lone pairs 4. you show any charges Your structure need not be that of an actual or chemicallypossible molecule. (10 pts) b) onsider the following molecules: Molecule #1 Molecule #2 Molecule #3 2 N S S Rank the three molecules in order from the most hydrophobic to the most hydrophilic. te that they are not amino acids. Write your answers in the blanks below (6 pts.) Most ydrophobic Most ydrophilic ancer 17

8 Question 2; continued; NTE TAT A TABLE F AMIN AID STRUTURES AN BE FND N PAGE 12. c) Show below is the structure of the amino acid aspartic acid. 2 N i) Give the name of one amino acid whose side chain can form a hydrogen bond with the side chain of aspartic acid. If more than one amino acid is possible; give only one. (4 pts) ii) n the figure above, draw the relevant part(s) of the side chain of the amino acid you named in part (i) forming a hydrogen bond with a relevant part of aspartic acid. Indicate the hydrogen bond with a dashed line. You need not draw the entire amino acid; just enough so we can clearly identify the part of the amino acid that you mean. (4 pts) iii) Give the name of one amino acid whose side chain can form an ionic bond with the side chain of aspartic acid. If more than one amino acid is possible; give only one. (4 pts) d) Give the names of two amino acids whose side chains can interact with each other via a hydrophobic interaction. There are many possible right answers here; give only one amino acid per blank. (4 pts) ancer 18

9 Question 3: Genetics, Biochemistry, and Molecular Biology (28 points) NTE TAT TERE IS A TABLE F TE GENETI DE N PAGE 13. emoglobin is the protein that carries oxygen in red blood cells. emoglobin is made of 4 protein chains: 2 αglobins and 2 βglobins. Defects in βglobin can lead to various blood disorders. Two common disorders are: emolytic Anemia: severe missense mutations (for example, changing a hydrophobic amino acid to a hydrophilic one) often result in a fulllength βglobin that is severly misfolded. These severely misfolded proteins stick together and damage the red blood cells resulting in hemolytic anemia. emolytic anemias are inherited as autosomal dominant diseases. Thalassemia: mutations that result in dramatically shorter or absent βglobin protein result in nonfunctional hemoglobin. This nonfunctional hemoglobin cannot carry oxygen but does not damage the red blood cells. Thalassemias are inherited as autosomal recessive diseases. The next four questions will ask you to predict the phenotype of particular mutations. As a hint, you should know that: 1 of the mutants would be expected to produce normal βglobin 1 of the mutants would be expected to produce hemolytic anemia 1 of the mutants would be expected to produce thalassemia a) In the normal βglobin gene, the DNA for codon #27 is G; which encodes ala. In hemoglobin Volga (b Volga ), there is a mutation that changes this codon to GA; all other bases are unchanged. i) What will be the effect of the mutation described on the amino acid sequence (1 o structure) of the βglobin produced by the b Volga allele? (3pts) ii) What will be the effect of the change you described in (i) on the fullyfolded structure (3 o structure) and function of the βglobin produced by the b Volga allele? (2 pts) iii) What would you expect the phenotype of b Volga to be? ircle one and explain your reasoning. (Remember the hint in the box above). (3 pts) Explanation: normal hemolytic anemia thalassemia ancer 19

10 Question 3, continued: b) In the normal βglobin gene, the DNA for codon #17 is AAG, which encodes lys. In hemoglobin hina (b hina ), there is a mutation that changes this codon to TAG; all other bases are unchanged. i) What will be the effect of the mutation described on the amino acid sequence (1 o structure) of the βglobin produced by the b hina allele? (3 pts) ii) What will be the effect of the change you described in (i) on the fullyfolded structure (3 o structure) and function of the βglobin produced by the b hina allele? (2 pts) iii) What would you expect the phenotype of b hina to be? ircle one and explain your reasoning. Remember the hint in the box on page 6. (3 pts) Explanation: normal hemolytic anemia thalassemia ancer 110

11 Question 3, continued; c) In the normal βglobin gene, the DNA for codon #60 is GTG, which encodes val. In hemoglobin Yatsushiro (b Yatsushiro ), there is a mutation that changes this codon to TG; all other bases are unchanged. i) What will be the effect of the mutation described on the amino acid sequence (1 o structure) of the βglobin produced by the b Yatsushiro allele? (3 pts) ii) What will be the effect of the change you described in (i) on the fullyfolded structure (3 o structure) and function of the βglobin produced by the b Yatsushiro allele? (2 pts) iii) What would you expect the phenotype of b Yatsushiro? ircle one and explain your reasoning. Remember the hint in the box on page 6. (3 pts) Explanation: normal hemolytic anemia thalassemia d) You have discovered a new blood disorder that is due to a defect in the βglobin gene; you call it b Boston. A pedigree for this disorder is shown below: Based on the data given in this problem, which type of disorder is b Boston likely to be? ircle one and explain your reasoning. (4 pts) hemolytic anemia thalassemia Explanation: ancer 111

12 Question 4: ancer (20 points) a) For each of the cells described below, predict whether or not the cell would grow in the presence or absence of growth factor. ircle the appropriate answers and explain your reasoning. A normal cell is shown as an example. (5 pts each) (i) rmal ell ell A cell where both copies of the gene for p53 produce proteins that are always inactive. Explanation: Will cell grow without growth factor? Will cell grow with growth factor? (ii) A cell where both copies of the gene for the receptor produce no protein at all. Explanation: ancer 112

13 Question 4, continued: a) continued: (iii) rmal ell ell A cell where both copies of the gene for the receptor produce a receptor protein that is always inactive. In addition: one copy of the gene for ras produces a ras protein that is always active; the other copy of the gene for ras produces a protein that is normal. Explanation: Will cell grow without growth factor? Will cell grow with growth factor? b) ertain people who inherit an increased ability to repair damaged DNA have a decreased risk of cancer. Explain this observation. ancer 113

14 Summary hart: If you see.. Part of molecule You should think... Properties nonpolar phobic no no yes nonpolar phobic no no yes N polar philic ª no polar philic ª no S nonpolar phobic no no yes polar philic ª yes no N polar philic ª yes no P polar philic ª no S nonpolar phobic no no yes S polar philic ª no N philic no yes no N S philic yes no no philic no yes no philic yes yes no phobic no no yes tes: * Assuming a suitable partner is nearby. ª If the or N is charged, yes ; if not no., if the N or has a lone pair available. Since this is an atom, not a bond, it is neither polar nor nonpolar. ancer 114

15 STRUTURES F AMIN AIDS 3 N 3 ALANINE (ala) N 3 ARGININE (arg) N N 2 N 2 2 N N 2 3 ASPARAGINE (asn) 2 N 3 ASPARTI AID (asp) 2 S N 3 YSTEINE (cys) 2 2 N 3 GLUTAMI AID (glu) 2 2 N 3 GLUTAMINE (gln) N 2 N 3 GLYINE (gly) 2 N 3 N ISTIDINE (his) N N ISLEUINE (ile) 2 N 3 LEUINE (leu) N 3 N 3 LYSINE (lys) 2 2 S 3 N 3 METININE (met) N3 3 TRENINE (thr) 2 N 3 2 N 3 PENYLALANINE (phe) TRYPTPAN (trp) N 2 N 3 2 N 2 2 PRLINE (pro) TYRSINE (tyr) 2 N 3 SERINE (ser) 3 3 N 3 VALINE (val) ancer 115

16 The Genetic ode: U A G U A G UU ser UAU tyr U ser UA tyr UA ser UAA STP UG ser UAG STP UUU phe UU phe UUA leu UUG leu UU leu U leu UA leu UG leu AUU ile AU ile AUA ile AUG met GUU val GU val GUA val GUG val U pro pro A pro G pro AU thr A thr AA thr AG thr GU ala G ala GA ala GG ala AU his A his AA gln AG gln AAU asn AA asn AAA lys AAG lys GAU asp GA asp GAA glu GAG glu UGU cys UG cys UGA STP UGG trp GU arg G arg GA arg GG arg AGU ser AG ser AGA arg AGG arg GGU gly GG gly GGA gly GGG gly U A G U A G U A G U A G ancer 116

17 Solutions to Fall 2006 Final Exam 1) a) Autosomal recessive b) allele contribution to phenotype D normal (dominant) d disease (recessive) c) #1: Dd #2: Dd #3: dd #4: Dd #5: Dd d) ½; Dd X dd gives ½ chance of dd (needed to show Punnett square or equivalent) 2) a) Many possible structures; here is one: b) N c) i) (any one of) arg, asn, gln, his, lys, ser, thr, trp, tyr ii) many possible structures; here s one with serine: backbone 2 2 backbone iii) his, lys, or arg d) (any pair of these) ala, cys, gly, ile, leu, met, phe, pro, trp, tyr, val 3) a) i) alanine aspartic acid ii) Alanine is phobic; aspartic acid is philic this will likely disturb the phobic core of the protein and make it fold improperly. iii) emolytic anemia the protein will be fulllength but nonfunctional. With the improper folding, it could form eintz bodies like b hristchurch, which leads to hemolytic anemia. b) i) lysine STP codon ii) the protein will only be 16 amino acids long with ~90% of the protein missing, it cannot be functional. iii) Thalassemia the protein is present but dramatically shorter than normal. c) i) valine leucine ii) both are phobic, so likely no effect on function iii) rmal since little change in amino acid properties. d) This shows autosomal dominant inheritance; therefore, it is likely to be hemolytic anemia. 4) a) i) Without p53, the DP s will always be made and the cell will always divide (yes, yes) ii) Without functional receptor, the cell cannot be signaled to divide (no, no). iii) Even though the receptor is inactive, ras comes after it in the pathway; active ras will make the cell divide always. (yes, yes) b) More DNA repair means less frequent mutations. Less frequent mutations make cancer less likely. ancer 117

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