Chris Inglehearn
Understanding the causes of eye diseases
Our work aims to determine the causes of human visual defects and to find out more about normal eye function. Ultimately we aim to contribute to the search for cures for blinding diseases.
One major area of research is in autozygosity (homozygosity) mapping to identify mutations causing recessively inherited diseases. We carried out an empirical investigation of the theoretical basis of this technique (Woods et al. 2006) and used it to identify a strong candidate for the LCA5 gene, defective in Leber congenital amaurosis. Leber amaurosis is the commonest form of congenital blindness and is an autosomal recessive disorder that displays considerable locus heterogeneity. With colleagues from the Netherlands we identified lebercilin, a ciliary and microtubule-associated protein whose gene is mutated in LCA mapping to chromsome 6q.
In addition we played a major role in an international collaboration which identified
SLC4A11 as the defective gene in corneal hereditary endothelial dystrophy (Vithana et al. 2006).
We also continue our ongoing interest in determining the cellular basis for splicing factor retinitis pigmentosa. Finally, we translate research findings into a clinical setting by piloting diagnostic services for inherited retinal diseases, in collaboration with clinical colleagues.
Recent publications:
Den Hollander A, Koenekoop R, Mohamed M, Arts H, Boldt K, Towns K, Sedmark T, Beer M, Nagel-Wolfrum K, McKibbin M, Dharmaraj S, Lopez I, Ivings L, Williams G, Springell K, Woods CG, Jafri H, Rashid Y, Strom T, Zwaag B, Gosens I, Kersten F, Veltman J, Van Wijk E, Zonneveld M, Beersum S, Maumenee I, Wolfrum U, Cheetham M, Ueffing M, Cremers F, Inglehearn CF, Roepman R (2007). Mutations in lebercilin, a novel ciliary protein, cause Leber congenital amaurosis. Nature Genet 39:889-95
Vithana E, Morgan P, Sundaresan P, Ebenezer N, Tan DT, Mohamed MD, Anand S, Khine KO, Venkataraman D, Yong V, Salto-Tellez M, Venkataraman A, Guo K, Hemadevi B, Srinivasan M, Prajna V, Khine M, Casey JR, Inglehearn CF, Aung T (2006). Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endothelial dystrophy (CHED2). Nature Genet 38:755-7
Woods CG, Springell K, Hampshire D, Mohamed M, McKibbin M, Cox J, Stern R, Raymond F, Malik S, Karbani G, Ahmed M, Bond J, Clayton D, Inglehearn CF (2006). Quantification of homozygosity in consanguineous individuals with autosomal recessive disease. Am J Hum Genet 78:889-96
Pal B, Mohamed M, Keen T, Williams G, Bradbury J, Sheridan E, Inglehearn CF (2004). A new phenotype of recessively inherited foveal hypoplasia and anterior segment dysgenesis maps to a locus on chromosome 16q23.2-24.2. J Med Genet 41:772-7
Keen T, Mohamed M, McKibbin M, Rashid Y, Jafri H, Maumenee I, Inglehearn CF (2003). Identification of a locus for Leber's congenital amaurosis on chromosome 1p36. Eur J Hum Genet 11:420-3
AutoSNPa is a powerful graphical tool for identification of autozygous regions.