1. Keratoconus genetics research at CERA Tuesday 24 November 2015 Professor Paul Baird Ocular Genetics Unit TRANSLATIONAL GENOMICS

2. Keratoconus – a genetic involvement Few genes replicated in more than one study so limited data to work with

3.  We would like to identify genes that influence the disease process - Disease progression - Response to treatment - Allow for detection of risk genes in children - Pre-diagnosis

4. Ways we are identifying KC genes 3 approaches being used: Genes from corneal curvature from a myopia study - some of these genes appear associated with KC - establishing an international consortium eg HK RNA Sequencing - allows all expressed genes to be assessed Family studies - need KC families

5. Keratoconus tissue Control tissue cornea Various molecular steps RNA Sequencing Extract RNA from tissue sample Run samples on sequencing machine Compare KC and control samples for differences

6. Is this a true figure? Sporadic vs familial detection of early changes needs good imaging analysis eg Pentacam

7. Assessing family history in Keratoconus

8. Keratoconus Family 2 issues Unaffected individuals do not want to participate Unaffected individuals may have mild KC without knowing – need to image

9. Keratoconus appears to have multiple genes – need to look for genes turned on/off - RNA Seq Need more individuals from KC families Need advanced imaging for detection of early changes to allow a better determination of family history Putting these findings together will allow a better understanding of disease and help improve patient care Key points

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