A new method for long-range haplotype phasing with short-read sequencing data.

DESCRIPTION provided by applicant A key challenge to the integration of genomics into the clinical setting is the ability to link genomic variation within a chromosome i e to separat and characterize the two copies of a genome present in a diploid cell This linkage process known as haplotype phasing is difficult to accomplish using the short read high throughput sequencing technologies in routine use today Haplotype phasing is critical for many clinical genomics interests including linking compound heterozygote variants within disease associated genes and untangling complex genomic rearrangements frequently found in cancers Attempts to circumvent the limitations of short read sequencing in haplotype phasing by using longer read sequencing technology are in the early stages of development and years from routine use Given the demand for haplotype phasing in the clinical setting new approaches that can immediately leverage proven short read sequencing technologies are needed Dovetail Genomics has developed and generated preliminary feasibility data for a method that generates short read sequencing libraries for phasing haplotypes This technique promises more complete contiguous and accurate haplotype characterization than existing approaches and does so simply and affordably In order to successfully develop the concept and continue to demonstrate feasibly the following two goals will be met First computational models will be used to determine the parameters required for haplotype phasing with the method and these parameters will be tested and adjusted Second the methodandapos s capacity to phase haplotypes and reconstruct reference genome standards at high accuracy and completeness will be tested Successful demonstration of feasibility will permit further development of the method with the goal of developing a commercially viable kit and complementary software analysis suite for clinical genomics PUBLIC HEALTH RELEVANCE The integration of genomics into the clinic and medicine remains challenging due to technological shortcomings with sequencing technology In particular long range genomic information suitable for linking genomic variants in studies of genetic disease remains elusive We propose to test the feasibility of a technology that will overcome these limitations and improve health outcomes for genetic disorders and cancers