The 200 Mammals Project: Sequencing Genomes by a Novel Cost-Effective Method, Yielding a High-Resolution Annotation of the Human Genome

One of the most difficult challenges in the medical genomics field is the correct interpretation of GWAS peaks and identifying causative genomic changes.  Comparative genomics has been shown to be a powerful tool to help with this issue, providing evidence for functionality in the genome by using conservation data across species.  Combining this data with GWAS peaks can prioritize genomic changes for follow-up functional studies, especially for non-coding mutations, which make up 88% of disease-associated GWAS loci.

Previously, the 29 Mammals project yielded 12bp resolution of conserved elements.  From this data we can extrapolate that ~200 mammals are needed to reach single basepair resolution.  There are roughly 50 high quality mammalian assemblies, and the Broad Institute is leading an effort to bring that number up to 200 in a cost effective manner.

To this end, the Broad Institute is developing a new assembly algorithm, DISCOVAR, a graph-based assembly method that relies on data from a single PCR-free Illumina library as its input.  Pilot data has shown that we achieve very high base-quality scores, full polymorphism/variant information for every base, larger contig sizes and most importantly, similar gene content as extant assemblies.

Once produced, these additional genome assemblies will provide a valuable research resource and enable a wide range of analysis on the resultant data set to refine the annotation of the human genome, including constraint measurements, detection and annotation of RNA structures and conserved regulatory motifs, gene family expansions/contractions and accelerated regions across the mammalian lineages.