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The DNA Bead String Exercise Anita L DeStefano, PhD Department of Biostatistics BU School of Public...
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Transcript of The DNA Bead String Exercise Anita L DeStefano, PhD Department of Biostatistics BU School of Public...
The DNA Bead String Exercise
Anita L DeStefano, PhDDepartment of BiostatisticsBU School of Public Health
Co-Director Biostatistics ProgramAssociate Director Genome Science Institute
Innovation Inspiration
• National Heart Lung and Blood Institute (NHLBI) funded Summer Institute in Training in Biostatistics (SIBS)
• 6 week intensive summer course for undergraduates
• Addressing dearth of Biostatisticians
Innovation Inspiration
• Modules in –Biostatistics–Epidemiology–Clinical Trials–Statistical Genetics
Innovation Inspiration
• Modules in –Biostatistics–Epidemiology–Clinical Trials–Statistical Genetics
Lisa Sullivan, Chair Department of BiostatisticsAssociate Dean of Education, SPHMetcalf Award Winner
Wayne LaMorte, Assistant Dean of Education, SPHPresenting later today
Me
Innovation Inspiration
• Need to keep up with excellent faculty– Hands on activities– Counting M&M colors to assess statistical
distribution• I teach the last week
– Even highly motivated students start to wane a bit
Innovation Inspiration
• Statistical Genetics– Application of statistical tests to genetic data– Often to identify variation in the human genome
that confers risk for disease– Requires understanding of both the statistical and
genetic concepts• SIBS students have varying background in
biology and genetics
How do I…
• Provide a hands on way to “see” DNA?• Show students how DNA is analyzed without
taking them into a lab?• Bring students of varying background to the
same level• Cover both genetic and statistical concepts?• Have students interact with each other?• Have students interact with me?
DNA Bead Exercise
• In the laboratory can examine a small segment of DNA and characterize
• Recreated a small DNA segment with beads incorporating key genetic concepts– Non-coding region– Promoter region– Coding region– Restriction enzyme cut site– Tetranucleotide repeat– Single Nucleotide Polymorphism (SNP: missense)
• Carefully constructed to incorporate statistical concepts– Disease association– Linkage disequilibrium
ATGC
GATA repeat
promoter region
codons
String color indicates disease status
ECOR1 cut site
ECOR1 cut site
Single Nucleotide Polymorphism SNP
DNA Bead Exercise: Implementation
• Randomly hand out bead strings to student– Half blue strings (unaffected with disease)– Half yellow strings (affected with disease)
• Students must pair based on same string color• Characterize their “individual”
– Affected/Unaffected with disease– Length of DNA segment (based on GATA repeats)– Presence or Absence of ECOR1 cut site– Amino Acid sequence
• Aggregate data across the class
ATGC
GATA repeat
promoter region
codons
String color indicates disease status
ECOR1 cut site
ECOR1 cut site
DNA Bead Exercise: Implementation
• Discuss correct statistical test– No association with disease status
Allele (Length of Bead String: varies by number of GATA repeats)80 84 88 92 96
Affected 2 1 4 2 3
Unaffected 1 2 3 3 3
Table 1. Allele Frequencies based on 12 individuals (24 chromosomes)
DNA Bead Exercise: Implementation
• Create similar tables for other genetic characteristics
• Association between presence/absence of ECOR1 cut site and disease status
• Stronger association between amino acid change and disease status
• Correlation between the ECOR1 cut site and amino acid change– Linkage disequilibrium
DNA Bead Exercise: Implementation
• Exercise used in– Summer Institute for Training in Biostatistics
(undergraduates)– SPH BS858 Statistical Genetics I (graduate students)– Upward Bound (high school students)
• Well received by students• Helps achieve learning objectives• Could be adapted for your course in genetics,
medical genetics, population genetics, bioinformatics