Upload
derry
View
18
Download
0
Tags:
Embed Size (px)
DESCRIPTION
Mouse eyes and vision research consortium. Prof Marcela Votruba PhD FRCOphth Prof Ian Jackson PhD. Ocular Genetics. 4 newly visually impaired children each day in UK Every day 100 people in the UK start losing their sight. First early modern description of a genetic disease: - PowerPoint PPT Presentation
Citation preview
MRC Mouse Network Jan 2012
Mouse eyes and vision research consortium
Prof Marcela Votruba PhD FRCOphth
Prof Ian Jackson PhD
MRC Mouse Network Jan 2012
Ocular Genetics
4 newly visually impaired children each day in UKEvery day 100 people in the UK start losing their sight
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
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!
MRC Mouse Network Jan 2012
Investigators Cardiff:
PI: Professor Marcela Votruba: optic neuropathies & mitochondrial disease Professor James E Morgan: glaucomasDr Jez Guggenheim: myopia and refractive errors
Edinburgh: PI: Professor Ian Jackson: eye phenotype analyses on mutagenised miceProfessor David FitzPatrick: developmental eye disordersProfessor John West: cornea
Oxford: Professor Russsell Foster: circadian clocksProfessor Robert E MacLaren: inherited retinal disease & retinal degeneration
Bristol:Professor Andrew Dick: inflammatory eye diseasesDr Denize Atan: retinal development
Southampton: Prof Andrew Lotery: age related macular degeneration
Leeds: Professor Chris Inglehearn: retinitis pigmentosa
MRC Mouse Network Jan 2012
Themes
• Ocular development• Ocular ageing• Neurodegeneration
• Cornea• Retina• Optic nerve
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
MRC Mouse Network Jan 2012
Principal Aims
• To identify the pathways thatunderlie normal eye function andhow these are disrupted in disease
• To provide platforms fortherapeutic developments
• To integrate basic scientists andclinicians and human geneticists
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
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
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.
MRC Mouse Network Jan 2012
MRC Mouse Network Jan 2012
MRC Mouse Network Jan 2012
Translational impact