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LENScience Senior Biology Seminar Series Huntington's disease: Understanding a mutation Questions and Discussion Pre‐seminar School Discussion This seminar focuses on the role of mutations in disease. The disease explored is Huntington’s disease (HD), a disease of the brain caused by the inheritance of a mutated autosomal dominant allele of the Huntington’s gene. During the seminar we will explore the concept of mutation, and look at how scientists are using a range of resources to understand the mutation and its effect on the body, The seminar will provide an opportunity for you to review concepts of gene expression, mutations and stem cells, explore the use of different biotechnologies, and consider the ethical questions that are faced by scientists as they work to understand a disease and find a potential cure. A very special part of this work is the partnership that the scientists have with patients and their families that are affected by Huntington’s disease. The seminar will show you something of the journey of question, uncertainty and discovery that scientists are undertaking to find out more about this disease. You will be introduced to the concept of epigenetics, a relatively new concept that scientists are discovering more and more about. Epigenetics helps us to understand the relationship between genes and the environment. The epigenome describes those factors outside the genome that control which genes are turned on and off. They are like switches. This seminar will help you explore both the way in which genes are turned on and off and the way in which the environment can effect molecular switches. The scientists involved in this research are from two multidisciplinary research organisations within New Zealand: The Centre for Brain Research and the National Research Centre for Growth and Development. 1 Use your knowledge of Y12 Biology and the information in the seminar paper to discuss the following questions. 1. Protein synthesis is a two stage process involving transcription and translation. Explain what happens in each stage of protein synthesis. 2. Scientists talk about coding and non‐coding DNA. What do these terms mean? 3. What does the term GENE EXPRESSION mean? 4. Describe the relationship between DNA, RNA, and proteins and explain how mutations can impact on phenotype. 5. Describe a situation where the effect of environment on phenotype can be observed and potentially reversed if the environment changes. 6. Describe a situation where the effect of environment on phenotype can be observed and cannot be reversed if the environment changes. 7. Discuss the difference between the situations in 6 and 7 above. 8. Review your understanding of gene mutations. Define a gene mutation and explain why some mutations are neutral while others cause a change to the protein synthesised by the gene. Level 3 Achievement Standards linking to this seminar: AS 90714 Biology 3.2 Research a contemporary biological issue AS 90715 Biology 3.3 Describe the role of DNA in relation to gene expression Key Concepts from Level 3 Biology that link to this seminar: Below are selected objectives from the Year 13 biology programme that link to this seminar. THESE ARE NOT A FULL LIST OF THE CONCEPTS IN YOUR COURSE. You may wish to review these concepts before the seminar. Gene Expression / Genetics: 
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Describe DNA in terms of structure and function Describe the process of DNA replication and the role that enzymes have in this process Describe the process of protein synthesis and the role of DNA and enzymes in the production of proteins Describe the role of DNA in gene expression and the determination of phenotype Describe the control of gene expression at the transcriptional level in prokaryotes and eukaryotes Describe the role of metabolic pathways in the control of gene expression Explain the role of gene‐gene interactions (epistasis, collaboration and polygenes) in determination of phenotype. Explain the potential effect of environment on expression of genes (although this is not a specific objective from the Y13 programme, understanding of this concept will allow you to understand metabolic pathways and control of gene expression—e.g. think about how the lac‐operon is controlled by the presence or absence of lactose). Copyright © Liggins Institute 2011 http://LENS.auckland.ac.nz 2 Post Seminar Challenge Questions 1. Huntington’s Disease is caused by a gene mutation of the IT15 gene on chromosome 4. The pattern of inheritance is autosomal dominant. 2. Compare and contrast autosomal dominant, autosomal recessive, sex linked dominant, and sex linked recessive inheritance patterns and discuss the relationship between inheritance patterns of a disease and the likelihood of offspring being affected by the disease. The IT15 gene shows variation in the number of CAG repeats between individuals. In a normal allele there are between 10 and 35 CAG repeats, whereas in the mutant allele there can be 36 or more CAG repeats. 3. 4. Using your understanding of gene expression and protein structure, explain the impact of additional CAG repeats on the structure of the huntingtin protein. Evidence from research shows that there is both genotypic and phenotypic variation present in Huntington’s disease. Some aspects of this variability can be explained while other aspects are not well understood. a. Using information presented in the seminar paper, discuss aspects of the phenotypic variability seen in HD that can be explained to some extent by research evidence. b. Scientists at the University of Auckland are currently exploring the possibility that HD may involve alterations to epigenetic processes. Explain what the epigenome is and discuss potential effects of alterations in epigenetic processes on structure and function within an organism. Scientists have identified that the human brain has adult stem cells and that when affected by HD, the human brain tries to repair itself by making replacement brain cells (a process called neurogenesis). While the potential to replace diseased brain cells using stem cells is exciting, the research is still in the phase of development and understanding whether this is potentially viable or not will take many years. Compare and contrast the potential of embryonic and adult stem cells as future treatment options for neurological disease, examining both biological and ethical issues associated with this potential. Login and contribute your answers at http://lens.auckland.ac.nz/index.php/Seminar_1_2011_Discussion_Page Copyright © Liggins Institute 2011 http://LENS.auckland.ac.nz 3 LENScience Senior Biology Seminar Series Huntington's disease: Understanding a mutation Post Seminar Challenge Questions 1. Huntington’s Disease is caused by a gene mutation of the IT15 gene on chromosome 4. The pattern of inheritance is autosomal dominant. 2. Compare and contrast autosomal dominant, autosomal recessive, sex linked dominant, and sex linked recessive inheritance patterns and discuss the relationship between inheritance patterns of a disease and the likelihood of offspring being affected by the disease. The IT15 gene shows variation in the number of CAG repeats between individuals. In a normal allele there are between 10 and 35 CAG repeats, whereas in the mutant allele there can be 36 or more CAG repeats. 3. 4. Using your understanding of gene expression and protein structure, explain the impact of additional CAG repeats on the structure of the huntingtin protein. Evidence from research shows that there is both genotypic and phenotypic variation present in Huntington’s disease. Some aspects of this variability can be explained while other aspects are not well understood. a. Using information presented in the seminar paper, discuss aspects of the phenotypic variability seen in HD that can be explained to some extent by research evidence. b. Scientists at the University of Auckland are currently exploring the possibility that HD may involve alterations to epigenetic processes. Explain what the epigenome is and discuss potential effects of alterations in epigenetic processes on structure and function within an organism. Scientists have identified that the human brain has adult stem cells and that when affected by HD, the human brain tries to repair itself by making replacement brain cells (a process called neurogenesis). While the potential to replace diseased brain cells using stem cells is exciting, the research is still in the phase of development and understanding whether this is potentially viable or not will take many years. Compare and contrast the potential of embryonic and adult stem cells as future treatment options for neurological disease, examining both biological and ethical issues associated with this potential. Login and contribute your answers at http://lens.auckland.ac.nz/index.php/Seminar_1_2011_Discussion_Page Copyright © Liggins Institute 2011 http://LENS.auckland.ac.nz 4