Identifying Disease Genes using BLAST
(Basic Logical Alignment Search Tool)
Briarcliff High School
Westchester, New York
Summer Research Program for Science Teachers
Course: Living Environment (New York State Regents Curriculum)/Biology
Grade Level: 9th and 10th (may also be adapted for 11th and 12th grade classes)
Objectives: Students will be able to:
§ Navigate the National Center for Biological Information (NCBI) website and BLAST program
§ Compare a given nucleotide sequence with known sequences in BLAST
§ Analyze the results of a BLAST search
§ Identify human disease genes using a BLAST search
§ Determine the chromosomal locations of genetic disease genes
§ Discuss the underlying mutation(s) and clinical features associated with certain genetic diseases
§ Explain the potential applications of using BLAST and other online genetic databases
Introduction: Given the increasing role of computers in processing large amounts of information, it is important for students to understand the potential applications of bioinformatics and its impact on science, medicine, and society as a whole. This activity provides a hands-on learning experience for students using an online database accessed every day by countless numbers of research scientists all over the world, and is most suitable towards the end of a unit on genetics.
(This lesson was adapted from The American Biology Teacher, Volume 65, No. 8, October 2003.)
§ Index cards with sample nucleotide sequences for known disease genes
§ One Teacher Computer Station (with Internet access)
§ LCD projector
§ SMART Board™ (lesson can be modified if not available)
§ Computers with Internet access (enough for students to work in groups of 2)
Time Required: Two 40-minute periods (may take longer or shorter, depending on time constraints and logistics of using computers and accessing the Internet); Steps 1-5 for the 1st period, Steps 6-7 for the 2nd period)
1) Using a computer hooked up to an LCD projector (preferably with a SMART Board, but not necessary), go to the NCBI website, found at http://www.ncbi.nlm.nih.gov/, and project this web page up front for the class to see (preferably on a SMART Board, but a whiteboard/screen will also do). After explaining briefly what the NCBI does, click on the word “BLAST”, located on the dark blue bar near the top of the page.
2) Under the heading “Nucleotide”, click on the link for “Nucleotide-nucleotide BLAST”. Review briefly what nucleotides are, asking them to name the 4 different nucleotide bases in DNA, and then enter the letters “ATCG” into the large empty “Search” box. When you finish typing, click on the “BLAST!” button, and after it brings you to the next screen, click on the “Format!” button.
3) After waiting a few seconds for the results to appear on the screen, discuss why there was “No significant similarity found” as stated on the bottom of the page. At this time, you may invite students to submit another sample query by listing a random sequence of 4-8 nucleotide bases, discussing further the reasons for a result similar to the first one, and the relationship between the number of nucleotides entered and the specificity of matches found in the database (touch on probability/statistics, presence of repetitive DNA elements, etc.).
4) Distribute the index cards with the sample nucleotide sequences to the different lab groups, one card per group. Tell the class that each group has a different sequence for a possible human genetic disease, and that they are going to use the BLAST program to determine the identity of the disease gene they were given.
5) Now hand out the Identifying Disease Genes Worksheet and use it to provide a brief overview of the activity, telling them that they are expected to complete it by the end of the class period (or for homework, depending on time constraints and your personal preference).
6) Have each group of students report to the class the results of their BLAST search, making sure to discuss the identity of their assigned disease gene, the chromosomal location of their gene, and the underlying mutation(s) and clinical features associated with the disease.
7) Close the lesson by getting student feedback on the activity and discussing the potential applications of using BLAST and other online genetic databases (studying evolution by comparing sequences from different organisms, privacy issues and insurance, potential careers in bioinformatics, etc.).
New York State Math, Science, and Technology Learning Standards met by this lesson:
§ Standard 1: Analysis, Inquiry and Design – Students will use mathematical analysis, scientific inquiry, and engineering design, as appropriate, to pose questions, seek answers, and develop solutions
§ Standard 2: Information Systems – Students will access, generate, process, and transfer information using appropriate technologies
§ Standard 4: Science – Students will understand and apply scientific concepts, principles, and theories pertaining to the physical setting and living environment and recognize the historical development of ideas in science
§ Standard 5: Technology – Students will apply technological knowledge and skills to design, construct, use, and evaluate products and systems to satisfy human and environmental needs
§ Standard: Interdisciplinary Problem Solving – Students will apply the knowledge and thinking skills of mathematics, science, and technology to address real-life problems and make informed decisions
National Science Learning Standards met by this lesson:
§ Content Standard A: As a result of activities in grades 9-12, all students should develop abilities necessary to do scientific inquiry and understanding about scientific inquiry
§ Content Standard B: As a result of activities in grades 9-12, all students should develop understanding of the structure and properties of matter, chemical reactions, motions and forces, and interactions of matter and energy
§ Content Standard C: As a result of activities in grades 9-12, all students should develop understanding of the molecular basis of heredity, and matter, energy, and organization in living systems
§ Content Standard E: As a result of activities in grades 9-12, all students should develop abilities of technological design and understandings about science and technology
§ Content Standard F: As a result of activities in grades 9-12, all students should develop understanding of science and technology in local, national, and global challenges
§ Content Standard G: As a result of activities in grades 9-12, all students should develop understanding of the nature of scientific knowledge