About

Our group focuses on the driving genetic factors behind rare and developmental disorders. Our current research can be divided three major compartments: 1. Inherited Retinal Disease, 2. General Developmental Disorders and 3. Disorders of Sex Development. We  have active projects on Stargardt Disease, North-Carolina Macular Dystrophy and Blepharophimosis syndrome. We leave no stone unturned and use state-of-the-art laboratory techniques to investigate at both the genomic (single nucleotide variations, structural variants and copy number variations) and the epigenomic (regulatory elements, non-coding RNAs and epigenetic modifications) level. For functional analyses we use commercially available cell lines, patient-derived cells as well as frog and zebrafish in vivo models (Xenopus tropicalis and Danio rerio). It is our hope that by mapping the complex (epi-)genetic landscape of rare diseases as thoroughly as possible, future patients can enjoy better treatment options and a better quality of life.

AJHG ​Award for Outstanding Trainee Publication

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Dr. Stijn Van De Sompele will receive the prestigious price for outstanding trainee publication, granted by the American Society for Human Genetics (ASHG), during the annual ASGH meeting in Washington (1-5  Nov 2023)

​Congratulations Stijn!

King Baudouin Foundation Grant

Prof. Elfride De Baere, received a generous fund granted by the King Baudouin Foundation last week. This grant will be used for further research studies in our research group on functional genomics in the retina. 

FWO PhD fellowship

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Last week, 3 PhD fellowships were granted to our team members, Kyana Van Acker,
​Lieselot Vincke & Charlotte Matton.

​Congratulations to all!

NEW PAPER ALERT

By Alfredo Duenas Rey & Victor Lopez Soriano
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Cross-species genome comparisons have revealed a substantial number of ultraconserved non-coding elements (UCNEs). Several of these elements have proved to be essential tissue- and cell type-specific cis-regulators of developmental gene expression. Here, we characterized a set of UCNEs as candidate CREs (cCREs) during retinal development and evaluated the contribution of their genomic variation to rare eye diseases, for which pathogenic non-coding variants are emerging. Integration of bulk and single-cell retinal multi-omics data revealed 594 genes under potential cis-regulatory control of UCNEs, of which 45 are implicated in rare eye disease. Mining of candidate cis-regulatory UCNEs in WGS data derived from the rare eye disease cohort of Genomics England revealed 178 ultrarare variants within 84 UCNEs associated with 29 disease genes. Overall, we provide a comprehensive annotation of ultraconserved non-coding regions acting as cCREs during retinal development which can be targets of non-coding variation underlying rare eye diseases.
By Alexandre Segers

​RNA-sequencing (RNA-seq) is increasingly used to diagnose patients with rare diseases by prioritising genes with aberrant expression and/or splicing. State-of-the-art methods for detecting aberrant expression and splicing, however, are extremely slow. The latter, also discard much information because they only use junction reads to infer aberrant splicing. In this contribution, we show that replacing the offset for library size unlocks conventional bulk RNA-seq workflows for fast and scalable differential usage, aberrant splicing and expression analyses. Our method, saseR, is several orders of magnitude faster than the state-of-the-art methods and dramatically outperforms these in terms of sensitivity and specificity for aberrant splicing, while being on par with these inferring differential usage and aberrant expression. Finally, our framework is also very flexible and can be used for all applications that involve the analysis of proportions of short- or long RNA-seq read counts. 
By Alfredo Duenas Rey

​This study focuses on the significance of 5' untranslated region (5'UTR) variants in inherited retinal diseases (IRDs). It presents a comprehensive approach involving the analysis of retinal RNA data for 378 IRD genes, assessment of 5'UTR coverage in whole exome sequencing data, and evaluation of 5'UTR variants in large patient cohorts. The study identified 11 potentially pathogenic variants in 10 genes, with two of them validated as having functional effects. Notably, the MERTK:c.-125G>A variant reduced luciferase mRNA levels and activity, while the RDH12:c.-123C>T variant, found in conjunction with another reported variant, resulted in reduced RDH12 protein levels. This research underscores the importance of 5'UTR variants in IRDs and offers a systematic strategy for annotating and validating such variants, applicable to other inherited diseases.
NEW PAPER ALERT

​By Dr. Eva D'haene & Victor Lopez Soriano

Through extensive comparative 3D genome mapping, based on genome-wide (Hi-C), promoter-centric (HiChIP) and locus-specific (UMI-4C) assays of human neural retina and RPE, we have shown that gene regulation at key IRD loci is likely mediated by tissue-specific chromatin interactions. These findings do not only provide insight into tissue-specific regulatory landscapes of IRD genes, but also delineate the search space for non-coding genomic variation underlying unsolved IRD.
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De Baere Lab © 2020