By Andy Goren, CEO Dermagenoma Presentation from the World Vitiligo Symposium 2011. Sponsored by the VR Foundation.

1. Vitiligo Genetics:
scientific discovery to clinical utility
Presented by:
Andy Goren, CEO
DermaGenoma, Inc.
Wednesday, July 6, 2011

2. Venue
Vitiligo World Symposium
IV Russian Congress of Dermatovenerology
July 7, 2011
Saint Petersburg, Russia
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3. Disclosure Statement
Employee of DermaGenoma, Inc. - a company that develops
and markets diagnostic and therapeutic products for cosmetic
dermatology
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4. Overview
• The information stored in each person’s cell nucleus
holds the promise for early disease screening,
preventive treatment and perhaps cure to some
diseases
• To date the main effort focused on associating coding
regions of DNA with disease state
• Discoveries of new associations between phenotype and
genotype are made almost daily
• Are there any clinical implications to vitiligo?
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5. Common Genetic Terms
• SNP - single nucleotide polymorphism
• Sequencing - determine continuous sequence of
DNA
• GWAS - Gene Wide Association Study
• Gene wide “scan” using of high density SNP Chip
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6. The Human DNA
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7. Genetic Association Studies
• Prior to starting a genetic study we review the
hereditary evidence for the phenotypical trait
• Generalized Vitiligo (GV) suggest an inheritance
model mediated by other factors
• Sibling risk in Caucasians approximately 6% or 16x
increased risk (0.38% prevalence)
• Concordance in monozygotic twins is 23%
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8. Genetic Association Studies
• We then study disease etiology/pathogenesis to
identify plausible genes or epigenetic mechanisms
• In GV immune related genes may be of interest
• We select patients with GV and normal controls
• Patient selection is often the limiting step in
finding and replicating genetic association
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9. Genetic Association Studies
• We either sequence a very specific region or gene
or perform a gene wide SNP “scan”
• Gene wide scans are good for broad discovery, but
tend to result in weaker associations
• We statistically associate GV phenotype with the
genetic variances
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10. Genetic Association Studies
• Select patients with GV and normal controls
• Use a SNP chip to discover association
Fig. 1. A patient with generalized
vitiligo. Note obvious patches of white skin
in typical distribution involving the perior-
bital region and hands.
have yet been identified with certainty. This limited progress has resulted, in 10
large part, from the lack of a clear definition of the disorder and the lack of a
Wednesday, July 6, 2011 tractable experimental animal model of typical human generalized vitiligo that

11. Genetic Association Studies
• Results are often conflicting due to improper
patient selection. GV presents a significant
challenge due to diagnostics
• Good rule of thumb is a minimum of 3 replicated
studies
• Additional markers are not always additive
• A high Relative Risk or increased risk with a low
prevalence usually has little clinical value
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12. Clinical Utility
• The DNA is a blueprint to one’s life hence has
potential predictive power
• Can we use genetics to screen for a disease?
• Will the screening change the course of therapy?
• Can we use genetics to diagnose for a disease?
• Can we use genetics to predict treatment outcome?
(PGx)
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13. Clinical Utility - Example
• Can we use genetics to screen for GV?
– To date traditional genetic association studies
are not able to find a clinical useful screening
model for GV
– GV prevalence is low (less then 1%)
– GV inheritance is not very strong (MZT 23%) i.e.,
environmental affects are strong
– Increased Risk not clinically useful
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14. Clinical Utility - Example
• Can we use genetics to screen for GV?
– New approach is needed
– Epigenetic could be influenced by environment
– Chicken model (feather depigmentation) induced
demethylation exhibits auto-immune symptoms
(Sreekumar et al)
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15. Clinical Utility - Example
• Can we use genetics to screen for GV?
– Abnormal DNA methylation in peripheral blood
mononuclear cells in GV patients (Zhao et al)
– My group recently published AR epigenetics in
female AGA. New evidence emerging in male
AGA
– My group is embarking on a new cutaneous
tissue methylation map study. Promising for GV
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16. Clinical Utility - Example
• Can we use genetics to predict treatment outcome?
– NB-UVB and PUVA are common treatments for GV
– Approximately 50% of patients respond to
phototherapy. Expensive and time consuming.
– We recently completed a phototherapy response
genetic study in psoriasis
– p53 homozygous alleles strongly predict response in
psoriasis (90% PPV)
– We plan to next study the p53 pathway in GV
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17. Future Developments
• Better understanding of the basic science of DNA -
epigenetics and marker interaction
• Full “nucleus” mapping and sequencing
• Discovery of new therapeutic targets (not always
same as screening or diagnostic markers)
• ICD type classification not rich enough to describe
molecular variants
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18. Q&A
Andy Goren, President & CEO
DermaGenoma, Inc.
e-mail: andyg@dermagenoma.com
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