The DNA Bead String Exercise

1. The DNA Bead String Exercise Anita L DeStefano, PhD Department of Biostatistics BU School of Public Health Co-Director Biostatistics Program Associate Director Genome Science Institute

2. 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

3. Innovation Inspiration • Modules in • Biostatistics • Epidemiology • Clinical Trials • Statistical Genetics

4. Innovation Inspiration Lisa Sullivan, Chair Department of Biostatistics Associate Dean of Education, SPH Metcalf Award Winner • Modules in • Biostatistics • Epidemiology • Clinical Trials • Statistical Genetics Wayne LaMorte, Assistant Dean of Education, SPH Presenting later today Me

5. 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

6. 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

7. 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?

8. DNA Bead Exercise • In the laboratory can examine a small segment of DNA and characterize • Recreated a small DNA segment with beadsincorporating 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

9. promoter region codons ECOR1 cut site A T G C String color indicates disease status ECOR1 cut site GATA repeat

10. Single Nucleotide Polymorphism SNP

11. 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

12. promoter region codons ECOR1 cut site A T G C String color indicates disease status ECOR1 cut site GATA repeat

13. DNA Bead Exercise: Implementation Table 1. Allele Frequencies based on 12 individuals(24 chromosomes) • Discuss correct statistical test • No association with disease status

14. 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

15. 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