Transcript Microbes R the Biosphere? - Georgia Institute of Technology

Georgia Tech School of Biology
A $1,000 human genome sequence?
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Georgia Tech School of Biology
DNA sequencing and genomic medicine
Nicholas Volker
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Georgia Tech School of Biology
Clinical presentation
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Georgia Tech School of Biology
The case history
Born October 2004
First abscess near rectum in 2006, hole (fistula) appears
that leaks stool
2007 -symptoms resemble Crohn's disease (IBD), but
medical, surgical, diet treatments fail. Colostomy. More
fistulas. Sepsis. ER, antibiotics, blood transfusions.
2008 – more inflammation, fistulas, no diagnosis
2009 – By fall, more than 300 days (250 consecutive) at
hospital, 100 operations. Out of options, out of clues.
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The roles
Nick's pediatrician
Nick's parent (mom or dad)
Nick's older sibling
Institutional Review Board member
Georgia Tech School of Biology
Discussion: should Nick's DNA be sequenced?
For each of the roles, what questions would the person have?
What would he/she want to know? What concerns or worries?
Georgia Tech School of Biology
The decision: should Nick's DNA be sequenced?
What are the odds that his DNA sequence will be useful? What
might be learned?
What are the financial costs?
Who will pay?
Who else has a stake in Nick's DNA sequence?
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Work out a protocol:
1. What should be sequenced: exome, whole
genome, or just certain genes?
2. Who gets the results? Privacy and data
security?
3. What information should be returned to the
family?
4. What should be published and/or publicized?
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First look at sequencing results
Over 16,000 variants (differences from reference
genome)
Is there a way to sift these variants according to how
likely they are to cause Nick's disease?
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Georgia Tech School of Biology
Georgia Tech School of Biology
Mutation in the XIAP gene
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Georgia Tech School of Biology
The XIAP gene
Regulation of cell death
Regulation of gut immune system
X-linked
Mutation in gene leads to extremely rare disease called
XLP, inability to fight Epstein-Barr virus, death by
age 10. Only cure is bone marrow transplant.
Nick's copy of gene has one base change:
A TGT codon changed to TAT
How does this affect Nick's XIAP protein?
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Nick’s mutation changes a key amino acid
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Georgia Tech School of Biology
Bone marrow transplant for Nick
For each of the roles, discuss questions and
concerns.
How might each person react and feel about the
results thus far?
Georgia Tech School of Biology
Would you get your genome sequenced?
• What would motivate you to get your genome
sequenced?
• What would you want to know about your genome?
• What information, if any, would you want withheld?
• Who would you share the information with?
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