Genetics science utility by Andy Goren


Published on

By Andy Goren,
CEO Dermagenoma

Presentation from the World Vitiligo Symposium 2011. Sponsored by the VR Foundation.

  • Be the first to comment

  • Be the first to like this

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Genetics science utility by Andy Goren

  1. 1. Vitiligo Genetics: scientific discovery to clinical utility Presented by: Andy Goren, CEO DermaGenoma, Inc.Wednesday, July 6, 2011
  2. 2. Venue Vitiligo World Symposium IV Russian Congress of Dermatovenerology July 7, 2011 Saint Petersburg, Russia 2Wednesday, July 6, 2011
  3. 3. Disclosure Statement Employee of DermaGenoma, Inc. - a company that develops and markets diagnostic and therapeutic products for cosmetic dermatology 3Wednesday, July 6, 2011
  4. 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? 4Wednesday, July 6, 2011
  5. 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 5Wednesday, July 6, 2011
  6. 6. The Human DNA 6Wednesday, July 6, 2011
  7. 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% 7Wednesday, July 6, 2011
  8. 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 8Wednesday, July 6, 2011
  9. 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 9Wednesday, July 6, 2011
  10. 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 aWednesday, July 6, 2011 tractable experimental animal model of typical human generalized vitiligo that
  11. 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 11 9Wednesday, July 6, 2011
  12. 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) 12Wednesday, July 6, 2011
  13. 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 13Wednesday, July 6, 2011
  14. 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) 14Wednesday, July 6, 2011
  15. 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 15Wednesday, July 6, 2011
  16. 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 16Wednesday, July 6, 2011
  17. 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 17Wednesday, July 6, 2011
  18. 18. Q&A Andy Goren, President & CEO DermaGenoma, Inc. e-mail: 18Wednesday, July 6, 2011