Exploiting Single Nucleotide Polymorphisms for Extreme Performance

Advances in DNA sequencing technology have generated a rapid expansion of human genome information and the revelation of extraordinary individual-level genetic variation. Individual genome sequencing will soon be routine and cost-effective. To exploit this resource to the benefit of warfighters, we propose an approach for identifying and characterizing genetic variants that compromise metabolic efficiency (and ultimately physical and cognitive performance), yet are amenable to nutritional optimization. There are 600+ cofactor-dependent enzymes in the human proteome, and preliminary studies provide ample precedence for the remediation of dysfunctional enzyme variants by straightforward vitamin/mineral supplementation. We describe a technology platform in which all possible enzyme variants are functionally assessed and pre-determined for each enzyme/gene. These datasets will serve to rapidly identify carriers of variant enzymes who can metabolically benefit from cofactor supplementation. In Phase I, the approach will be developed on a single high-value target gene, Cystathionine beta-Synthase, necessary for homocysteine clearance and cardio-respiratory fitness. These studies will facilitate Phase II to query all genes related to homocysteine clearance, and to spur a field trial in which individual genotype and metabolite profile are diagnostic for potential performance enhancement. This pioneering work will render genome sequence an asset to improve health, fitness and readiness.