Sustainability and economic consequences of creating marine closed areas in a multi-species and multi-activity context


Subhajyoti De
(University of Colorado School of Medicine)

2014/2/17, 15:00- at The 1st meeting room of the Biology Department (Room1203, 2nd floor of the main building of the Faculty of Sciences)


Genomic alteration such as point mutations, amplification or deletion of genetic material is a hallmark of many cancer types, but the mechanistic basis behind the genome-wide landscape of such events is poorly understood. Using cancer genomics and high dimensional data analysis approach we address this topic at the two levels - the 3D nuclear architecture and DNA secondary structure. In the first part of my talk, we show that DNA replication timing patterns, chromatin organization, and long-range interactions in the nucleus can predict the genome-wide distributions of not only point mutations, but also amplifications, deletions, and loss of heterozygosity events. This is noteworthy since the boundary-pairs of large genomic alterations may be far apart on the linear DNA and the region in between may not be replicated at the same time. Our results provide mechanisms for generation of genomic alterations, and suggest that nuclear architecture and DNA replication timing data can help identify a significant proportion of such events. In the second part, we focus on the sequence context of the boundaries of the genomic alterations. We observe a significant enrichment for one type of DNA secondary structure, called G-quadruplex (G4) in the vicinity of the boundaries and find evidence for a causal role of G4s in generation of many of these events. Notably, abnormal loss of DNA methylation near G4-rich regions is a common signature for many such boundaries. We propose a mechanistic hypothesis that abnormal loss of methylation in genomic regions enriched for G4s acts as a mutagenic factor driving tissue-specific mutational landscapes in cancer. Together, our findings add momentum to the ongoing debate about epigenetic origin of cancer.


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