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Molecular Genetics Laboratory

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Maria Solaki

Surname Solaki
First name Maria
Position and Title PhD student
Project Functional assessment of CNGA3 variants using an aequorin-based bioassay

Business address

Molecular Genetics Laboratory
Institute for Ophthalmic Research
Centre for Ophthalmology,
University of Tübingen
Elfriede-Aulhorn-Strasse 7
D-72076 Tübingen,

Phone: +49 (0)7071 29-80706

E-mail: maria.solaki[at]med.uni-tuebingen.de

Project descriptions

Functional assessment of CNGA3 variants using an aequorin-based bioassay

Achromatopsia (ACHM) is a rare autosomal recessive retinal disorder characterized by absent color discrimination, severely reduced visual acuity, photophobia and nystagmus. To date, mutations located in six genes, mainly playing an important role in the cone phototransduction machinery, have been associated with ACHM in humans. Identification of variants in patients with inherited retinal diseases is nowadays facilitated by high‑throughput sequencing technologies such as disease targeted gene panels and whole exome sequencing. However, assessing the potential pathogenicity of the identified variants remains challenging hampering genetic diagnosis and identification of patients eligible for gene supplementation trials.

My project aims to establish an expert-based assessment of mutations and genotypes for CNGA3 which is one of the major genes implicated in achromatopsia. CNGA3 encodes the A‐subunit of the cyclic nucleotide‐gated (CNG) channel in cone photoreceptors and accounts for up to 33% of ACHM cases in the European population. To develop an efficient scoring system for CNGA3 variants, we will be performing an in silico analysis using data from bioinformatic prediction tools and population databases to classify the pathogenic potential of the identified CNGA3 variants.

Following the in silico analysis, mutant homomeric CNGA3 channels will be assessed using an aequorin-based bioassay in transiently transfected human embryonic kidney cells (HEK293T). To analyze the functionality of mutant versus wildtype homomeric CNGA3 channels, the applied in vitro assay uses the Ca2+-sensitive photoprotein aequorin to detect the luminescence signal triggered by the ligand-activated calcium influx. Finally, we will compare the results obtained in the in silico analysis with our functional data to validate the in silico classification of the examined CNGA3 variants.