1 BIO 208 Worksheet 4 The review is not comprehensive 2011 1. Match the mutation with the best answer A – J. Each answer is used once. _______G__ occurs in sperm or egg A. point mutation _________C occurs due to no particular agent B. any mutation ____E_____ occurs due to chemical or environment C. spontaneous mutation __F_______ does not result in an amino acid changeD. frameshift mutation ____H_____ causes the protein to be too short E. induced mutation ____D____ shifts the reading frame of the message F. silent mutation ______A__ involves one DNA base only G. germinal mutation ____B____ heritable change in DNA H. nonsense mutation ______I_ DNA triplet expansion I. trinucleotide repeat 2. Compare sequences # 1 and #2. Characterize each mutation (there are 4) as to position in the codon(1st, 2nd, or 3rd) and whether it is a transition (TS) or transversion (TV) Sequence #1 Sequence #2 (mutant) ATG GGA CCT ACA TAT GCC ATG GCA TTT ACA TAA GCC G-> C is a second position TV C-> T is a 1st position TS, the other is a 2nd position T-> A is a 3rd position TV 3. Characterize the mutations (a – e) using the following terms: Some of the mutations are described with more than one term Deletion Nonsense mutation a. TTC CAG AAA Point mutation Frameshift mutation Missense mutation Trinucleotide Repeat TTC CAG CAG CAG CAG CAG CAG CAG CAG AAA TRINUCLEOTIDE REPEAT b. ACTTTTGTTAAT c. ACTGTTAAT DELETION AUG CAG AUU AAC GCU GCA UAA met gln ile asn ala ala stop d. AUG CAG UCA AAC GCU GCA met gln ile asn ala ala e. AUG GAC UCA GCU met gln ile asn AUG AGA UUA ACG CUG CAU AA FRAMESHIFT + met arg leu thr leu his POINT MUT. AUG CAG UAA NONSENSE + POINT MUT met gln stop AUG met CAC his UCA ile GCU asn MISSENSE + POINT 4. What do the following acronyms stand for? UV SNP TS and TV 5. Fill in the correct number: 1 46 Cdk XP RB DNA SARS 2 2 20 4 3 billion 20,000 a. ____46__ chromosomes in a human somatic cell b. ___1___ human genomes in a single human cell c. ____2__ types of transitions that can occur d. ___3 billion___ nucleotide base pairs in the human genome e. __4-5____ approximate mutational events in the etiology of familial colorectal cancer f. ___4___ types of transversions that can occur g. ___2___ alleles mutated of RB to cause a loss of function h. ___1___mutations in the beta globin gene that cause sickle cell disease i. ___20___ amino acids in nature j. ___20,000___ genes in a human genome 6. Fill in - may use answer more than once or not at all Benign Apoptosis Oncogene Sickle cell a. b. c. d. e. f. g. h. i. j. k. l. m. n. o. p. q. r. s. Retinoblastoma Metastasis Angiogenesis Colon cancer Li Fraumeni Xeroderma pigmentosum Proto-oncogene Fragile X syndrome ANGIOGENESIS tumor releases molecule that interacts with blood vessel to promote vascularization RETINOBLASTOMA childhood eye cancer initiated when two alleles of RB gene are mutated BENIGN cancer forms in a connective capsule and is excised easily RETINOBL. sporadic and familial forms FRAGILE X trinucleotide repeat in gene promoter regions inactivates gene COLON CANCER cancer requires ~ 4 separate mutations to develop PROTOONCOGENE gene encodes a normal protein involved in cellular growth APOPTOSIS cell suffers DNA damage that is irreparable and is this pathway is initiated LI F. predisposition to cancer due to mutant p53 gene XERODERMA P. A number of malignant melanomas form due to mutant DNA repair system COLON CANCER, RETINOBLAS. Two cancers that involve mutant tumor suppressors SICKLE CELL occurs due to mutation in 6th codon of beta globin gene METASTASIS Movement of cancer cell from primary tumor to secondary location ONCOGENE A normal gene involved in cellular growth is mutated to this form XERODERMA P. extreme sensitivity to UV light SICKLE CELL misshapen red blood cells block capillaries XERODERMA P. mutation in DNA excision repair pathway FRAGILE X defect in signaling between neurons, lessens synaptic plasticity COLON CANCER polyp type tumor forms 7. Proteins. Fill in Telomerase p53 pRB Cdk cyclin ras EF2 Growth factor Growth factor receptor a. Telomerase enzyme immortalizes cells b. Ras a signal transducer involved in stimulating cell growth 3 c. d. e. f. g. h. i. j. k. l. m. n. o. p. q. E2F bound by pRB in inactive form Cyclin binds a CdK Ras a kinase that phosphorylates other proteins Growth factor, GF receptor, ras 3 proteins involved in stimulating cells to grow that when mutant are called oncogenes Growth factor receptor a transmembrane protein Telomerase acts at the ends of chromosomes Telomerase, p53, pRB, CDk, cyclin, ras E2F, GF, GFR = 9 proteins, a mutation in which can lead to cancer Growth factor a hormone is one type p53 can signal the cell to move to apoptotic pathway p53 pRB 2 tumor suppressor proteins Omit this one binds to mdm2 to target for degradation p53 mutations of gene encoding this protein observed in ~50% of cancers p53 and pRB knockout mice develop cancers early in life pRB interacts with E2F transcription factor omit this one free form results in an increase in the expression of p21 protein 8. Are the following associated with SNP or a gene (choose one for each) ? a. 90% of all human genetic variation SNP b. 20,000 estimated in human genome GENE c. 3 million estimated in human genome SNP d. contains introns and exons GENE e. transcribed as a unit of mRNA GENE f. may not be responsible for disease but may be used as a genetic marker SNP g. polymorphism SNP h. contains a promoter GENE 9. Fill in using the appropriate letter – each letter is used once A. Human Genome Project D. Pharmacogenomics G. DNA polymorphism B. Genetic predisposition E. Non-genetic factors H. Personalized medicine F. Presymptomatic testing D the study of how an individual’s genetic inheritance affects the body’s response to drugs H the ability to target a specific drug and dose to those individuals most likely to benefit B An allele which may predispose an individual to a developing a particular disease F A microarray test to test a person for disease before the development of noticeable disease symptoms A Governmental and private effort to determine the sequence of 3 billion nucleotides of human DNA G A small genetic change, or variation, that can occur within a person's DNA sequence E Behavior, lifestyle, diet, physical activity that influence gene expression and disease progression 10. Discuss the following cellular situations with respect to cell growth a. The cell cycle occurs too rapidly – will lead to abnormal, fast cell growth, too many cells, a benign tumor or a malignant tumor b. A DNA repair enzyme gene is mutated – mutations cannot be fixed. Because mutations are occurring and being fixed all of the time, this is serious. XP is an example of a disease in which a DNA repair system does not work. c. A tumor suppressor is overproduced. The cell will not divide. This is not related to cancer d. A growth factor receptor is overproduced. Too much growth factor will bind to the receptors and the cell may receive extra growth signal. Could lead to cancer. 4 e. A mutation in a growth factor gene causes too little growth factor to be produced. The cell will not divide. Not cancer related f. Angiogenesis is blocked. The tumor will not receive an adequate blood supply. It will shrink. g. Apoptosis does not occur in an abnormal cell. The abnormal cell will persist, can divide to 2 abnormal cells and so on. h. Normal mitosis occurs. Normal cell growth. i. A cell becomes transformed – it is a cancer cell. Exhibits the cancer phenotype. j. The RB gene promoter is nonfunctional due to a mutation. No promoter, no RB mRNA, n RB protein. No suppression of tumors – the cell will not arrest at the checkpoint and will continue without control in the cell cycle. k. A knockout mouse has 2 copies of a non-functional p53 gene l. A mouse is born with 1 functional copy of the p53 gene. One copy leads to enough p53 for the cell to remain normal in terms of phenotype. This mouse is at a high risk of developing cancer as if the other copy is mutated, it will lose the ability to regulate the G1-S checkpoint.