Dovetail Genomics Workshop – Solving Complex Genomic Challenges with a Multi-Dimensional View of the Genome
Saturday, June 15, 2019 | 10:00 AM – 11:30 PM | A4
Reconstructing shattered chromosomes and other applications for Dovetail™ Hi-C
Jannat Ijaz, BSc., Wellcome Sanger Institute, Cambridge, UK
Dovetail Genomics Technologies and Applications
Kai Kleiber, Dovetail Genomics, LLC, Scotts Valley, CA
Chromothripsis is a catastrophic genome reshuffling event in which tens to hundreds of structural variants occur in a single crisis. It is a major driver of cancer development in some tumour types such as sarcomas and some paediatric cancers. Chromothripsis provides a natural experiment to elucidate functional and epigenetic consequences of genome rearrangement. We selected 5 patient derived oesophageal adenocarcinoma organoid models with chromothripsis on which to build reference genome assemblies, coupled with comprehensive chromosome conformation mapping. These organoids contain massively restructured chromosomes, with fragments that have been fused together ranging from tens of bases to megabases.
We have sequenced these organoid cell lines at high depth using a range of sequencing technologies including Illumina x10, 10X Genomics, PacBio and Dovetail™ Hi-C chromosome capture. Integration of these different sequencing methods provides a more complete picture of the chromothriptic regions and has allowed us to reconstruct a highly shattered chromosome with over 800 rearrangements. As a result, we now have a better understanding of the mechanisms of chromothripsis and the generation of structural variants.