1. Human Genome Variation

a. Genetics of eye diseases

The main objective of this research group is to study sporadic and familial cases with ophthalmological, developmental or neurological disorders to improve the overall genetic diagnosis and provide targets for therapeutic interventions.  

Advanced DNA technologies including SNP-array, whole exome and genome sequencing are performed in patients and families to extract the relevant genetic information. State-of-the-art computational tools have been developed and bioinformatic pipelines have been employed to analyze the genomic data to identify the causative variants in the known and candidate genes.

The cellular and animal models are used to study the functional role of identified causative variants and their phenotypic consequences to elucidate the molecular mechanisms of the disease.

The aim is to develop a translational platform for hereditary diseases to enhance our understandings of new genes and to facilitate the development of various treatment options and personalized medicine for a diverse group of patients.

b. Genomic Database of homozygous variants

Our large scale genotyping and massively parallel sequencing efforts in consanguineous families are generating a valuable dataset which is helping to build-up a database representing inbred populations. We are recruiting samples from diverse consanguineous populations around the globe, to develop a unique comprehensive genomic database. This resource will serve as a one-stop shop genomic tool to study different attributes such as the ‘’runs-of-homozygosity’’, copy number variations, and to extract homozygous variants of interest.

The ultimate goal is to create an in-depth, publicly available database of genetic changes encompassing homozygosity to improve our understanding of various types of ‘variants of uncertain significance’ lying in different regions of the genome. All kinds of variants such as coding, variants located in regulatory regions, and variants affecting splicing will be documented in this database. This database will be useful for both research and diagnostic settings, and will be the best platform for the evaluation of ‘’human knockouts (i.e. with truncating mutations). The primary objective of this project is to extensively study and understand the functions and underlying mechanism of uncharacterized relevant coding and non-coding elements of DNA.   

2. Development of potential treatment approaches

The gene discovery project is extended towards the development of novel therapeutic approaches for rare eye disorders. A proof-of-concept study to treat a severe syndromic form of retinal and neurological phenotype, known as Cohen Syndrome (CS), which is caused by the biallelic pathogenic variants in the gene VPS13B, will be expanded to other similar disorders.

Mainly, three different approaches are being developed: (1) the use of antisense oligonucleotides (AONs) to induce skipping of exons that contain truncating variants, (2) the construction of minigenes by characterizing the essential domains of large size genes to make them suitable for gene replacement therapy especially in the retina (3) the use of small compounds, with major focus to be applied to the retina and the prevention of photoreceptor dystrophy.

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