Accurate, long read length, whole human genome sequencing under 100

DESCRIPTION (provided by applicant): The aim of this project is to investigate a simple method for slowing down the rate of electrophoretic translocation of DNA through a nanopore. Unique modulations of current across nanopores produced by individual basesduring such translocation forms the basis of DNA nanopore sequencing. The nanopore method requires very simple sample preparation with potentially no amplification steps and can achieve long read sequences with inexpensive hardware and biochemical reagents. Hence, nanopore technology holds a great deal of promise in the effort to achieve rapid, low cost sequencing. However, current high bandwidth methods are limited by the inability to accurately distinguish various bases due to the extremely rapid natureof freely translocating DNA. Methods proposed here maintain the simplicity of nanopore sequencing through biological and electronic innovations. Progress made through this proposal will potentially lead to an inexpensive and rapid benchtop DNA sequencing solution that will contribute significantly towards the goal of the 1000 genome. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: In this proposal, we use biological and electronic innovations to address critical issues that will enable the useof nanopores as viable tools in DNA sequencing. Due to its relative simplicity and low cost of instrumentation and materials, nanopore technology is considered a key piece of attaining the goal of sequencing genomes at low costs and in a rapid manner. This will have significant impacts on human health, including improved understanding of genetic causes of disease, development of personalized medicine, as well as faster identification of pathogens.