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Unformatted text preview: Bioseminar: NCCSTC A Family in Need: In-Class Case Study on Cancer Genetics Name: ​Sophia Selenou Date: ​4/24/17 Answer Sheet Part 1 – Genetic Testing ​Questions 1. Draw the pedigree for this family in the space provided below. Make sure to indicate Lee, the proband, with an arrow and use the proper symbol for individuals who have died from cancer. Remember to also label each generation with roman numerals. It is clear from the pedigree that there is a pattern. You strongly suspect that the high incidence of cancer in this family is caused by an inherited genetic defect. Due to the severity of the phenotype, the defective allele is probably rare in the population. 2. Complete the following table to help organize your thoughts. Indicate in the table if a mode of inheritance is definitely possible, possible but unlikely, or not possible based on the pedigree. Also briefly explain your rationale behind these choices in the space provided. Table 1 Determining the mode of Inheritance Mode of Inheritance Possible Possible but Unlikely Not possible Brief Rationale Autosomal recessive ​cancer is expressed a small percentage of the time. Autosomal dominant ​cancer is not expressed a majority of the time. X-linked recessive ​possible, but both parents would have to carry the gene. X-linked dominant expressed a small percentage of the time. ​cancer is Y-linked chromosomes only contributes to male parts. ​The Y Mitochondrial able to passed on by females. ​It would only be 3. What mode of inheritance pattern ​best ​fits this pedigree in your opinion? In my opinion, an autosomal dominant mode of inheritance best fits the mode of inheritance​. 4. What kind of information can you look up using the OMIM number for a genetic disorder? The genes involved, symptoms, and how it presents. 5. Based on the information from ​both your patient and his family, ​what genetic disorder should you most suspect? Li Fraumeni syndrome 6. What is the OMIM number for this disorder? 151623 7. What gene(s) is/are most often defective in this genetic disorder? TP53 8. Dr. Aikenhed shares your suspicion. She then shares with you her concerns about Leah and Luke, despite the fact that they do not appear to have cancer. Why is she concerned? Because his siblings have a chance of developing this cancer later in life. 9. With respect to this genetic disorder, would it be possible for a person with cancer to have two parents who do ​not ​have cancer? Explain. No. The parent(s) would have to have the gene in order to pass it on. Because the gene is dominant the parent(s) would have cancer as long as the gene is present. 10. Here are four general categories of tests along with four specific examples. Give the letter corresponding to the correct example after each category: Pre-implantation Genetic Diagnosis __​D​__ Carrier Testing __​A​__ Predictive (pre-symptomatic) Testing __​B_​ _ Prenatal Testing __​C​__ Examples​: A) Two parents are interested in learning their chances of having a child with Tay-Sachs disease. B) A 30-year-old man with a family history of Huntington disease wants to know if he carries the defective allele. C) Amniocentesis is performed in order to determine if a fetus has a major chromosomal disorder. D) A couple with achondroplasia want to ensure that they have a child who is unaffected by this condition. 11. What types of issues come up when determining whether to ​test ​someone for a genetic illness? The patient’s feelings about maybe causing someone in their family to have a disease. 12. If Lee has inherited a gene from his mother that predisposes him to cancer, would you recommend that the family test Leah and Luke at this point? Why or why not? Yes because they could start showing signs later in life and you’d want to take preemptive measures. Part 2 Questions 1. In order to test Lee for a genetic disorder, Dr. Aikenhed will probably take a sample of cells containing his genomic DNA by swabbing his cheek or taking a blood sample. Why is it important to use non-cancerous cells to test Lee for a genetic disorder instead of the biopsy tissue? The cancerous cells might have a different genetic sequence​. 2. Describe the main technique for amplifying a segment of DNA (like the one you suspect is involved in Lee’s cancer) from a complex mixture of genomic DNA. Remember that the entire human genome sequence is known. (​Hint: ​This is a technique that is commonly used by laboratories that do genetic testing and various other applications of molecular biology.) Polymerase Chain Reaction, the process of copying segments of DNA to be studied. 3. If Dr. Aikenhed wanted to see if there was mutation within the protein-coding sequence of the gene implicated in this disorder (as opposed to mutations affecting regulatory elements), what technique ​involving dideoxynucleotides ​could be used? Briefly describe this technique. Sanger sequencing, a method of DNA sequencing based on the selective incorporation of ddNTPs. 4. Frequent screening/check-ups and avoidance of risk factors (e.g., smoking) may be advised in cases involving inherited genes which predispose a person to cancer. Do you think that this advice will make a difference in morbidity or mortality related to this particular disorder? Why or why not? Yes because many types of cancer are greatly influenced by lifestyle choices and environmental factors. doing this keeps the body as healthy as possible. 5. What is the name of the genetic technique that would help a person who inherited this genetic disorder to have a child without the defective allele? Preimplantation screening/testing. Part III Questions 1. What can you conclude about gene expression in your patient’s cells? How is gene expression in your patient different than the other 5 patients? Lee has a low expression of the TP53 gene in his diseased compared to his normal cells. 2. The most common mutation for the genetic disorder affecting this family (occurring in ~72% of cases) involves the substitution of one amino acid for another in the protein. This type of change to the protein coding sequence is called a ​missense ​ mutation. There are two other types of common ​point ​mutations that affect the coding sequence of various proteins. Briefly describe all three types of mutations in Table 4 and include whether you predict that the level of mRNA and protein might be affected (increased or decreased). Create a Chart here Name of mutation How does mutation alter mRNA sequence? Could this mutation affect the level (increase or decrease)of functional protein in the cell? Why? Missense mutation substitution of one amino acid for another in the protein yes, it could increase or decrease because it changes the protein. Nonsense mutation the intended amino acid changes to a stop code. yes, the protein is terminated and is now useless. Silent mutation changes the nucleotide sequence but does not alter the amino acid sequence no the same proteins will be expressed Part 4 Questions 1. How would you describe the main goal of gene therapy to this family? The main goal would be to fix the mutation in this gene or just change/remove the gene all together. 2. Several different types of viruses, including adenoviruses, have been used as vectors for gene therapy in humans. Why are viruses used for gene therapy? The viruses can carry the new gene and infect the cells with it. 3. The two basic types of gene therapy are ​somatic cell gene therapy​ and ​germline therapy​. What is the main difference between them? Somatic cell gene therapy only effects the other body cells so it does not prevent the disease from occurring in the next generation. Germline therapy modifies the sperm and egg cells permanently preventing the disease from occurring in the next generation. 4. Which type would best help this patient and his family? Why? Germline therapy because it’s likely that it will keep occurring in the following generations. 5. If there were a current ​TP53 ​gene therapy clinical trial, would you recommend that Lee enroll in it? Why or why not? Yes because the therapy would be specific to his condition. Also, he is young and could probably withstand the treatment. 6. Write a brief, encouraging letter addressed to Lee and his family that highlights the hope of a future gene therapy cure for the disorder affecting them. Make sure you explain to them what gene therapy is and what your opinion is on the potential for it to cure LFS. Lee, I highly encourage you to stay optimistic while you are dealing with this disorder. Gene therapy is making great progress with trying to find a cure for mutations in genes such as yours. Some information on this process: Gene therapy is the transplantation of normal genes into cells in place of missing or defective ones in order to correct genetic disorders. I believe this could lead to a cure for you and your family because it will replace the mutated TP53 gene in your cells. I greatly encourage you to take this information into consideration. ...
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