Genome reconstruction and haplotype phasing using chromosome conformation capture methodologies.

Abstract

Genomic analysis of individuals or organisms is predicated on the availability of high-quality reference and genotype information. With the rapidly dropping costs of high-throughput DNA sequencing, this is becoming readily available for diverse organisms and for increasingly large populations of individuals. Despite these advances, there are still aspects of genome sequencing that remain challenging for existing sequencing methods. This includes the generation of long-range contiguity during genome assembly, identification of structural variants in both germline and somatic tissues, the phasing of haplotypes in diploid organisms and the resolution of genome sequence for organisms derived from complex samples. These types of information are valuable for understanding the role of genome sequence and genetic variation on genome function, and numerous approaches have been developed to address them. Recently, chromosome conformation capture (3C) experiments, such as the Hi-C assay, have emerged as powerful tools to aid in these challenges for genome reconstruction. We will review the current use of Hi-C as a tool for aiding in genome sequencing, addressing the applications, strengths, limitations and potential future directions for the use of 3C data in genome analysis. We argue that unique features of Hi-C experiments make this data type a powerful tool to address challenges in genome sequencing, and that future integration of Hi-C data with alternative sequencing assays will facilitate the continuing revolution in genomic analysis and genome sequencing.