Malte Spielmann
University Hospital Schleswig-Holstein
Germany

The Dark Side of the Genome: Challenges and Opportunities in the Post-Genomic Era

Clinical genome sequencing has become a reality in most European countries. However, more than 50% of rare disease patients remain without a molecular diagnosis even after undergoing advanced genomic testing. One possible reason for this gap is the lack of focus on the "dark side" of the genome—the 98% that is non-coding—which is often overlooked when diagnosing patients or studying cancer biology.

In my presentation, I will discuss the role of non-coding mutations and structural variants in causing human disease. Our research aims to understand the pleiotropic effects of these mutations and structural variants during embryogenesis, as well as their impact on the 3D architecture of the genome.
To achieve these objectives, we leverage cutting-edge, high-throughput technologies during mouse embryonic development, including single-cell analysis, chromosome conformation capture techniques, and massively parallel reporter assays.

Nicola Whiffin
University of Oxford
United Kingdom

The non-coding exome in rare disease: from diagnosis to therapies

Over 300 million people worldwide have a rare disorder. Currently, less than half of all individuals with a rare disorder receive a genetic diagnosis and even if the genetic cause of disease is known, over 95% of rare disorders have no specific treatments available. Current approaches to identify genetic diagnoses focus almost exclusively on regions of the genome that directly encode proteins, even when genome sequencing data are available. In this talk, I will discuss how studying gene regulation and genetic variants in regions of the genome that are exonic, but do not encode proteins (i.e. untranslated regions and non-coding RNAs) can identify new diagnoses for rare disease patients and help to develop treatments.

Zoltan Kutalik
University of Lausanne
Switzerland

Making sense of genetic associations

Genome-wide association studies have generated tens of thousands of associations between complex diseases and sequence variants. Despite the remarkable efforts of the past 15 years, the interpretation of these links and their clinical translation remains elusive.

I will explain how these vast amount of associations can be combined together (via extensions of the Mendelian Randomisation principle) in various fashions to learn about meaningful epidemiological phenomena (different disease consequences of various obesity subtypes), human behaviour (partner choice, parental rearing), biases in the data collection (due to study participation behaviour, self reporting errors), drug target- / biomarker genes.