RAPiD Genomics LLC — Department of Agriculture SBIR Phase I: 8.300000000000001

Description

Project Summary/AbstractProblem and Proposed Solution: Genomic selection or the ability to predict complexphenotypes using DNA information has tremendously accelerated animal breeding programs inrecent years. This revolutionary approach is already mainstream to breeding species such asdairy cattle in advanced programs. However further expansion of genomic selection to largerpopulations additional breeding programs underserved species and developing countriesrequires greater prediction accuracy at lower genotyping cost. The first challenge can beaddressed by whole genome re-sequencing to generate ultra-high-density DNA marker panels inthe training population. Unfortunately the species that would benefit the most from genomere-sequencing as a genotyping approach such as cattle pigs and fish species havenotoriously repetitive genomes. The drawback of sequencing genomes with high repetitivecontent is that a significant portion of the sequencing cost is spent characterizing theseuninformative regions. Up to 80% of the short-reads generated from a re-sequencing project maybe expected to map to high-copy regions and be discarded during bioinformatic analysis.Addressing the challenge of targeting genome re-sequencing to non-repetitive regions of thegenome will reduce cost increase throughput eliminate wasteful sequencing of non- informative regions improve the prediction accuracy of genomic selection and increaseaccess to the process to a wider range of producers. Furthermore directing sequencing to non- repetitive genic and regulatory regions is more likely to uncover variants that impact traits ofimportance. As a strategy to reduce costs further genomes can be sequenced at low sequencingdepth followed by imputation to solve the high missing data inherent to these approaches. Theproblem with this solution is that some markers associated with key genetic conditions andabnormalities cannot be inferred via imputation and remain missing. Therefore an ideal productfor whole-genome sequencing-based genotyping of cattle will involve depleting unwantedrepetitive elements but simultaneously enriching for key regions of the genome. The marketcurrently lacks a product that allows rapid and efficient elimination of repetitive regions fromgenomes while enriching for key variants and that can be readily integrated to standard re- sequencing pipelines.The goal of this SBIR Phase I is to determine the technical feasibility of GD-Seq aproduct to characterize the cattle genome using an improved whole-genome sequencing- based genotyping approach. Upon completion of the product we anticipate that regulatory andgenic regions of the genome will be enriched a minimum of 300-500% compared to standardWGS sequencing. Simultaneously the company expects to enrich markers associated with keytraits around 100 times. This will allow sequencing resources to be better allocated towardsimportant regions of the genome and key markers to be accurately genotyped even when the restof the genome is sequenced at low sequencing depth. This product presents a significantimprovement over current methodologies because it will solve major pain points currentlyassociated with SNP chips and other sequencing-based approaches.Anticipated Results and Commercial Applications: The commercial focus of thistechnical project is to facilitate the conversion of genotyping using DNA chip to a newgeneration of genotyping that relies on re-sequencing using GD-seq. The process is highlyscalable and automatable yet remaining cost-effective by improving sequencing data utilization.This provides the opportunities for more animals to be genotyped with higher marker densitywhich will support an industry that increasingly demands higher genetic gains especially onmore complex traits like feed efficiency fertility and animal health. A significant market existsfor this technology among animal