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 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 Lisa Sullivan, Chair Department of Biostatistics Associate Dean of Education, SPH Metcalf Award Winner
Biostatistics Epidemiology Clinical Trials Statistical Genetics Wayne LaMorte, Assistant Dean of Education, SPH Presenting 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 promoter region codons ECOR1 cut site A T G
C ECOR1 cut site GATA repeat String color indicates disease status 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 promoter
region codons ECOR1 cut site A T G C ECOR1 cut site
GATA repeat String color indicates disease status DNA Bead Exercise: Implementation Table 1. Allele Frequencies based on 12 individuals (24 chromosomes) 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 Discuss correct statistical test No association with disease status 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
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