Invited speakers

Prof. Isidro Cortes Ciriano

EMBL-EBI, UK

Research Group: Cancer Genomics
The group develops computational tools to characterise the mechanisms and consequences of genome instability processes in human cancers through the analysis of genome sequencing data from clinical samples and preclinical models using artificial intelligence and statistical methods. Our ultimate goals are to deliver computational tools in the field of cancer genomics to study cancer evolution and facilitate the discovery of novel biomarkers and therapeutic targets, and analytical methods applicable in clinical settings to improve cancer diagnosis and treatment selection.

Prof. Brunella Franco

Università degli Studi di Napoli “Federico II”, Napoli

Research Group: cell biology and disease mechanisms
Her laboratory focuses on the understanding of the molecular bases underlying rare diseases. Current research interests include Cilia and cilia associated disorders, the role of autophagy in cilia associated pathological conditions and disorders associated to mitochondria mediated neurodegeneration.

Prof. Christian Gilissen

Radboudumc University medical center, Nijmegen

Research Group: Genome Bioinformatics
He is working on the development and implementation of new genetic technologies and novel bioinformatics and AI algorithms for improving patient diagnostics, identifying novel genetic causes of disease and gaining fundamental understanding of genome variation.

Prof. Alexander Hoischen

Radboudumc University medical center, Nijmegen

Research Group: Genomic technologies for immune-mediated and infectious disease
He focuses on the application of the latest genomic technologies to understand human disease. A particular emphasis is put on the understanding of genetic defects that explain rare disease specifically immune diseases, such as inborn errors of immunity (IEIs).

Long-read read genomic technologies are strongly emerging. These include mapping technologies such as optical genome mapping (OGM), but also long-read sequencing (LRS) technologies, such as PacBio HiFi genome sequencing.

LRS allow to assess the full human genome for the first time and have the potential to revolutionize human genetics. This technology could offer a comprehensive first-tier test for clinical genetics and rare disease research. To determine the clinical utility of LRS, we performed Revio HiFi genome sequencing on 1,500 human genomes with ~30-fold coverage, including 100 mutation-positive controls that are impossible or challenging to identify by standard short-read genome sequencing, 100 severe sporadic rare disease cases as patient-parent trios, and 100 severe rare disease cases as singletons who remained undiagnosed after standard-of-care testing. Finally, we run a prospective clinical utility study of 1,000 samples representing the annual germline testing of our diagnostic division.

These studies suggest LRS could serve as a first tier generic test across many rare disease, and as such replace almost all standard-of-care assay for germline testing. In addition, LRS suggests an additional yield between 10-20% by previously hidden variants in several rare disease studies.

Prof. Alexandre Reymond

Center for Integrative Genomics, University of Lausanne

Research Group: Genome Structure and Expression
His laboratory has assessed the functional impact of genome structural changes, such as CNVs and balance rearrangements. His team demonstrated that expression levels of genes within CNVs tend to correlate with copy number changes, and that structural changes influence the expression of genes in their vicinity – an effect that may extends over the entire length of the affected chromosome. They provided initial evidence that CNVs shape tissue transcriptomes on a global scale and thus represent a substantial source for within-species phenotypic variation. His laboratory participated in disentangling the natural history of the 16p11.2 rearrangements, i.e. their evolution, associated phenotypes and identification of major driver genes.

Recurrent 600kb-long genomic rearrangements at 16p11.2 BP4-5 represent one of the most common causes of genomic disorders. They are mediated by human-specific duplications that appeared at the beginning of the modern human lineage, suggesting that their expansion has a possible evolutionary advantage that outweighs chromosomal instability.

These copy number variants (CNVs) are among the most frequent genetic causes of neurodevelopmental and psychiatric disorders, as they are found in 1% of individuals with autism spectrum disorders and schizophrenia. They were also originally associated with reciprocal defects in head size and body weight, but have since been associated with a plethora of phenotypic alterations, albeit with high variability in expressivity and incomplete penetrance. Revealing the complex and variable clinical manifestations of these CNVs is crucial for accurate diagnosis and personalized treatment strategies for carriers.

The 16p11.2 BP4-5 CNVs showcase variable expressivity and pleiotropy, as they are deleterious enough to be enriched in clinical cohorts but not enough so to be absent from population cohorts.