Transcript The DNA Bead String Exercise

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
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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