1. MRC Mouse Network Jan 2012 Mouse eyes and vision research consortium Prof Marcela Votruba PhD FRCOphth Prof Ian Jackson PhD

2. MRC Mouse Network Jan 2012 Ocular Genetics 4 newly visually impaired children each day in UK Every day 100 people in the UK start losing their sight

3. MRC Mouse Network Jan 2012 First early modern description of a genetic disease: –colour blindness, Dalton 1794 First disease mapped to a chromosome: –colour vision deficiency, X chromosome, Wilson 1911 First textbook of human genetics: ‘The human eye and its genetic disorders’ –Waardenberg 1932

4. MRC Mouse Network Jan 2012 First human disease linked to an autosome: –autosomal dominant cataract and the Duffy blood group, Renwick and Lawler 1963 First human disease to show digenic inheritance: –Retinitis Pigmentosa, Damji and Allingham 1997 Gene based therapies!

5. MRC Mouse Network Jan 2012 Investigators Cardiff: PI: Professor Marcela Votruba: optic neuropathies & mitochondrial disease Professor James E Morgan: glaucomas Dr Jez Guggenheim: myopia and refractive errors Edinburgh: PI: Professor Ian Jackson: eye phenotype analyses on mutagenised mice Professor David FitzPatrick: developmental eye disorders Professor John West: cornea Oxford: Professor Russsell Foster: circadian clocks Professor Robert E MacLaren: inherited retinal disease & retinal degeneration Bristol: Professor Andrew Dick: inflammatory eye diseases Dr Denize Atan: retinal development Southampton: Prof Andrew Lotery: age related macular degeneration Leeds: Professor Chris Inglehearn: retinitis pigmentosa

6. MRC Mouse Network Jan 2012 Themes Ocular development Ocular ageing Neurodegeneration Cornea Retina Optic nerve

7. MRC Mouse Network Jan 2012 Gene groups arising from investigators interests Ocular development –Coloboma –Anophthalmia/ microphthalmia –Retinal differentiation/ Prdm family Ocular ageing –Age related macular degeneration Cornea –Wound healing Retina –Retinitis pigmentosa –Other CRD/ RCD Optic nerve –Glaucoma genes –Optic neuropathy including

8. MRC Mouse Network Jan 2012 Principal Aims To identify the pathways that underlie normal eye function and how these are disrupted in disease To provide platforms for therapeutic developments To integrate basic scientists and clinicians and human geneticists

9. MRC Mouse Network Jan 2012 Objectives To establish novel phenotyping infrastructure at each centre according to expertise To capitalise on results from UK10K and DDD programmes of human genetics/genomics at the Wellcome Trust Sanger Institute which aim to find genes involved in human disease by patient genome sequencing To process lines in parallel in collaborative centres, depending on disease model To undertake groundbreaking research with translational impact To organize a collaborative meeting in early 2012 to prioritize genes and discuss models and new phenotyping To attract additional funding

10. MRC Mouse Network Jan 2012 Vision and ocular phenotyping Standard accepted tests: –Slit lamp –Ophthalmoscopy Possible additional screens: –Optokinetic nystagmus/ OKN –Ocular coherence tomography/OCT –electrophysiology/ERG –fundus autoflorescence/AF –fundus fluorescein angiography/FFA Potential future screens –Pupillary reflex Challenge niche tests –Circadian phase shift –More complex electrophysiology

11. MRC Mouse Network Jan 2012 Human disease gene identification The UK10K project –sequencing the exomes of 10,000 patients with a range of diseases –among them will be 100 patients with isolated coloboma and 25 with severe bilateral anophthalmia The Deciphering Developmental Disorders programme –will sequence 12,000 patients with developmental diseases which will include eye diseases, but the number is not fixed, or known. Some of the genes identified in these studies will be good candidates for later rounds of the KO programme.

12. MRC Mouse Network Jan 2012

14. Translational impact