Our group applies experimental and computational genomics approaches to study the extent,
functional impact, as well as mutational and evolutionary origins of genetic variants, particularly genomic structural variants (SVs).
SVs, which include copy-number variants (e.g. deletions/duplications) and balanced inversions, are the major form of genetic variation in humans accounting for most varying DNA bases between individuals.
Major objectives of the lab include to decipher the origin
and impact of SVs in healthy individuals and disease states, specifically in cancer. Our activities in international consortia, including the 1000 Genomes
Project and the Pan-Cancer Analysis of Whole Genomes (PCAWG) initiative, facilitate pursuing these objectives. We are particularly interested in understanding determinants of genomic DNA rearrangments, such as enhancer hijacking events (Northcott et al. Nature 2014
), androgen-associated rearrangements in prostate cancer (Weischenfeldt et al. Cancer Cell 2013
), or catastrophic DNA alterations also referred to as chromothripsis events (Rausch et al. Cell 2012
). We envision that breakthroughs in the genetic variation field will pave the way towards novel medical applications, enabling specific personalized treatments following
detailed assessment of patient genome sequences.
Our laboratory has also been investigating evolutionary determinants of DNA rearrangements, e.g.
in a recent survey of structural variation in several non-human primate species (Gokcumen et al. PNAS 2013
Heidelberg: One of the deadliest forms of paediatric brain tumour, Group 3 medulloblastoma, is linked to a variety of large-scale DNA rearrangements which all have the same overall effect on specific genes located on different chromosomes. The finding, by scientists at EMBL Heidelberg and collaborators, is published online today in Nature