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Identification and Analysis of Genes Associated with Inherited Retinal Diseases

  • Protocol
Retinal Degeneration

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1834))

Abstract

Inherited retinal diseases (IRDs) display a very high degree of clinical and genetic heterogeneity, which poses challenges in finding the underlying defects in known IRD-associated genes and in identifying novel IRD-associated genes. Knowledge on the molecular and clinical aspects of IRDs has increased tremendously in the last decade. Here, we outline the state-of-the-art techniques to find the causative genetic variants, with special attention for next-generation sequencing which can combine molecular diagnostics and retinal disease gene identification. An important aspect is the functional assessment of rare variants with RNA and protein effects which can only be predicted in silico. We therefore describe the in vitro assessment of putative splice defects in human embryonic kidney cells. In addition, we outline the use of stem cell technology to generate photoreceptor precursor cells from patients’ somatic cells which can subsequently be used for RNA and protein studies. Finally, we outline the in silico methods to interpret the causality of variants associated with inherited retinal disease and the registry of these variants.

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Acknowledgments

The work of M.K. is supported by the Rotterdamse Stichting Blindenbelangen, the Stichting Blindenhulp, the Stichting tot Verbetering van het Lot der Blinden, and the Stichting Blinden-Penning (to F.P.M.C and S.R.). The work of Z.F. is supported by the Foundation Fighting Blindness USA Project Program Award grant no. PPA-0517-0717-RAD (to F.P.M.C. and S.R.). The work of M.K. and S.C. is supported by the RP Fighting Blindness, UK, grant no. GR591 (to F.P.M.C.). The work of S.C. is supported by the Fighting Blindness, Ireland (to F.P.M.C. and S.R.).

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  1. Department of Human Genetics, Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands

    Mubeen Khan, Zeinab Fadaie, Stéphanie S. Cornelis, Frans P. M. Cremers & Susanne Roosing

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  1. Mubeen Khan
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  2. Zeinab Fadaie
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  3. Stéphanie S. Cornelis
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  4. Frans P. M. Cremers
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  1. Institute of Human Genetics, University of Regensburg, Regensburg, Germany

    Bernhard H. F. Weber

  2. Department of Ophthalmology, University of Cologne, Cologne, Germany

    Thomas Langmann

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Khan, M., Fadaie, Z., Cornelis, S.S., Cremers, F.P.M., Roosing, S. (2019). Identification and Analysis of Genes Associated with Inherited Retinal Diseases. In: Weber, B.H.F., Langmann, T. (eds) Retinal Degeneration. Methods in Molecular Biology, vol 1834. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-8669-9_1

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