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Developing and Applying Chromatin Proximity Ligation Methods

  • Author(s): O'Connell, Brendan L.
  • Advisor(s): Haussler, David
  • Green, Richard E
  • et al.
Abstract

Proximity ligation methods are a means of capturing long-range spatial information about DNA sequences with short-read sequencing compacted and concatenated DNA molecules. HiC, a method of gathering genome spatial information by the process of chromatin proximity ligation and capture, represents a powerful and versatile tool for modern genomics. Over the course of this dissertation, I demonstrate improvements to the HiC method and novel uses for the HiC data. An early novel use of chromatin proximity data was in the form of Chicago, an in vitro assembled chromatin version of HiC primarily used for de novo genome assembly scaffolding. This method was used to scaffold nearly one hundred new, high contiguity genome assemblies over the last two years. I next describe my own improvements to the HiC method, resulting in a faster, more economical version of HiC, and apply the improvements to explore the rapid-aging ICE mouse model and to scaffold a high-contiguity assembly of the Atlantic herring genome. I also show that the haplotype informative nature of HiC, when combined with recombined germline samples, allows for individual, personalized recombination maps, using both the Atlantic herring and human samples.

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