ARRA IMPACT REPORT:
Advanced DNA Sequencing Technology Program


Public Health Burden
When the Human Genome Project was completed in 2003, the cost to sequence a human genome was more than $10 million. NHGRI understood that human genome sequencing, far from being over, was just beginning, but that to conduct the research needed to dissect genomic contributions to disease, hundreds of thousands to millions of human sequences would be needed, so lowering the cost was a high priority. The resulting technologies have revolutionized the study of human genetic variation in studies ranging from the 1000 Genomes Project to The Cancer Genome Atlas and enabled the recently-initiated Centers for Mendelian Genomics. The focus of the sequencing technology program has shifted toward achieving human genome sequencing for $1,000 or less, which will offer the possibility of using genome sequence information in a routine healthcare setting.

NHGRI ARRA Investment in DNA Sequencing Technology Development
ARRA funding expanded the support for development of novel DNA sequencing technologies that will speed the discovery of heritable contributions to disease and will eventually enable individualized medicine. While ARRA support helped numerous investigators to advance a variety of DNA sequencing approaches, the two most dramatic advances are described here.

  • Not only the identity of the DNA subunit, called a nucleotide (A, T, C or G), is important for understanding genetic contribution to disease; also important is whether certain of those nucleotides have chemical groups attached. The most common attachments are methyl groups These nucleotide modifications can change the way in which particular DNA sequences are expressed and have been associated with normal and abnormal embryonic development and with diseases. Under ARRA support, the first method for directly determining the presence and identification of modified nucleotides as an integral part of the DNA sequencing process was developed.1   Results from the ARRA project include peer-reviewed publications, commercial applications notes, and software upgrades so that users of the vendor’s systems are able to determine DNA sequences in a way never before possible, directly from DNA purified from patients’ cells.
  • Initial demonstration of electronic DNA sequencing using a nanopore was enabled by an ARRA grant that supported painstaking studies on the manner in which the enzyme, DNA polymerase, may be used to control the movement of the DNA relative to the electronic sensor. DNA suspended in a nanopore interrupts the flow of ions through the pore, and that ion flow can be measured electronically. An ARRA-supported study reported, for the first time, electrical signals that correspond directly to the sequence of DNA subunits passing by the sensor.2 This DNA sequencing approach has been investigated for nearly 20 years, so the culmination of this research under ARRA support is particularly gratifying.

Contributing NIH Institutes & Centers

  • National Human Genome Research Institute (NHGRI)

  1. 1RC2HG005618-01 - TURNER, STEPHEN WHITFIELD - PACIFIC BIOSCIENCES OF CALIFORNIA, INC. - MENLO PARK - CA
  2. 1RC2HG005553-01 - AKESON, MARK A - UNIVERSITY OF CALIFORNIA SANTA CRUZ - SANTA CRUZ - CA