BTEC 3301 S15 ResearchProject

BTEC 3301 Spring 2015 Research Project Description

For your research project, you will research a human genetic disease through the application of bioinformatics methods to understand the disease, and current and future treatment regimes.

You will complete the project as a series of five tasks. Each task will be assigned to you following the completion of the related topic in class. You will turn in a 1-­‐2 page report for each task. Please remember that this is a research report, so do not submit a list of one/two-­‐line short answers. You should write full paragraphs to concisely describe the tasks accomplished. I am more interested in your interpretation of the results than the results themselves, so be sure to describe in detail your evaluation of the task, and when appropriate the statistical and biological significance of each result.

Please be sure to give web-­‐links (URL pointers) to the disease, gene, bioinformatics tools and all references and web sites used in your bibliography or as footnotes in your submitted task-­‐reports. Also please be sure to put any copied material in quotes with complete reference or URL pointer to the source of the material copied in your paper. Failure to properly reference source material, even from the Internet, is plagiarism and is considered academic dishonesty.

IMPORTANT NOTE: if you need assistance with writing your task reports in terms of writing skills related to logical organization of the material, vocabulary, expression of thoughts, language, grammar, and other general tips on writing research papers/reports. Please consult the UH Writing Center.

SUBMISSION DETAILS You will use TURNITIN LINKs on BBLearn to submit your reports for each task. The link will be provided on the Blackboard Learn Page closer to the submission deadlines.

Task 1: Disease Fact-­‐Sheet 1) You will be assigned a single gene, Mendelian disease from one of the Disease databases (Genes and Diseases, Genetics Home Reference, Gene Reviews, or Online Inheritance in Man (OMIM), or Gene Cards.

2) Your task is to create a disease fact that will briefly describe what is known about the genetic variations that cause that disease. Provide at least one mutation/deletion/duplication in the gene for the disease that is causative of the disease. Provide a basic description of the disease and its symptons (reference the URL to OMIM or Gene Reviews entry for your disease). Is there a classical (pre-­‐genetic) differential diagnosis of the disease or treatment of the disease? What is the world and ethnic distribution of the disease gene? 3) Complete a 2 page report. Page 1 will be the FACT SHEET, and page 2 will include your bibliography, and details of any searches conducted on PubMED/WoS/Google Scholar.

Task 2: Sequence Retrieval

1) Retrieve the genomic and/or mRNA sequence for the gene (normal). Review the Gene record (if available) in Entrez Gene and determine the structure and function of the gene. 2) Search the database to see if the corresponding genomic/mRNA sequence is available for the mutant/abnormal/disease. If yes, retrieve the sequence and save it as the “mutant sequence”. If not, create a mutant sequence based on the genetic mutation. 3) Retrieve the corresponding protein sequence. 1

4) Turn in a ½ -­‐ 1 page report on your search strategy for find the sequences, and list the AC#s of the DNA and protein sequences.

Task 3: Sequence Analysis

1) Analyze the gene sequence to determine number of exons/introns, mRNA transcripts and other features. 2) Search for the protein in UNIPROT or SWISSPROT. Identify the domains? Does the protein have a well-­‐understood biological function. You can check the biological functions of your protein choice by examining the Gene Ontology terms in the UniProt entry for your protein. How do the domains relate to the function of the protein. 3) Turn in a 1 – 2 page report on you're the structure/features of the DNA and protein sequences.

Task 4: Sequence Alignment 1) Perform a pairwise alignment of the abnormal sequence with the normal sequence (gene and/or protein). Justify the your choice of the tool, parameters and explain the results. 2) Turn in a 1½ -­‐ 2 page report describing the method used and explaining your results.

Task 5: Discussion

1) Prepare a 1-­‐page summary of your research (Tasks 1-­‐4) on the gene and the inferences you made from the sequence analysis. The summary should discuss: What is the causative genetic disorder? How does the mutated sequence compare to the normal? Did you find the mutation? Is it in a functionally or structurally important site? It is critical that you describe how the genetic variation may cause the disease. For example, is it by:

Ø A mutation within the coding region of the protein Ø A mutation altering gene expression by affecting the promoter Ø A mutation altering gene expression by affecting a transcription factor binding site Ø A mutation altering gene expression indirectly by mutating a transcription factor itself Ø A mutation altering copy number, hence changing gene expression levels Ø A mutation altering other regulatory sites (miRNA targets) Ø A mutation altering splice signals Ø Etc. … Often there will be several types of mutations that can cause the disease. Please comment on at least ONE type that is known for the disease. Justify the variation as a potential cause of the disease by supporting it with the sequence analysis you did in Task 3-­‐4. Are there any genetic tests available for the disease and/or any potential treatments. Are there any novel diagnostics that have resulted from knowing the genetics? Is there any novel understanding of the disease that has lead to novel therapy based on genetic knowledge.

References: (Use RefWorks to manage your citations and create your reference LIST in reports). Your bibliography can include: Ø Citations of articles

Ø Website for Tools Ø Note you can also cite the ORIGINAL RESEARCH PAPER describing the tool or database

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