Understanding the Mechanisms of Variant Effects in the Era of Genome Sequencing

Reductions in the costs of DNA sequencing have enabled inexpensive whole human genome and exome sequencing, thereby opening the era of precision medicine. However, these new advances in genome sequencing are necessary but not sufficient for understanding the origins of allelic variation in human genes and mechanisms of human genetic diseases and phenotypes. Although the majority of variants are likely to be neutral, a substantial fraction of them may explain the origins of Mendelian inherited disorders, inherited complex traits and diseases, as well as diseases caused by somatic mutations. However, finding functionally important variants and separating them from neutral polymorphisms remains a significant challenge.

Many computational and experimental methods have been developed to estimate the phenotypic effects of variants and this Gordon Conference will discuss new developments and approaches in this field. In parallel, significant efforts are being invested to catalog naturally occurring genetic differences, those found in the general population and those known to be disease-associated. The rapid growth of these databases and the current status of collection and categorization of genomic variation data will be another important topic of the conference. Database developers and researchers will have the opportunity to get together and bridge their research.

Another aspect of the conference will be addressed by the researchers working in the field of biological networks and pathways. Indeed, a defect in a single gene may sometimes be pathological, while in other cases a series of mutations in different genes are responsible for a disease. Can our understanding of biomolecular interaction networks contribute to predictions of the effects of disease mutations on cellular function? The conference participants will be able to share ideas about the interplay between molecular characteristics of individual network elements, effects of variants and networks’ topological properties.

In summary, the goal of this conference is to bring together researchers that work on diverse experimental and computational aspects related to inferring and analyzing the effects of human mutations on cellular function and their role in causing different diseases. It will help to advance the field by merging genomics and proteomics approaches, and by bringing together scientists who work on the same problems from different perspectives. We especially aim to provide a stimulating environment where students, postdocs and junior investigators can present and discuss their research with the best minds in the field. We believe the meeting will have significant impact on the research and development in the fields of human genetics, bioinformatics, translational and precision medicine.