BETHESDA, Md.--Bioinformatics will be a major component of one of the US National Human Genome Research Institute’s latest projects involving human DNA variation, said Robert Nussbaum, chief of the institute’s genetic disease research branch.
NHGRI, part of the US National Institutes of Health, has installed mass spectrometry equipment from Sequenom of San Diego, Calif., to assist in its research of single-nucleotide polymorphisms. Specifically, the institute is now using Sequenom’s MassArray system to identify and investigate SNPs in genes that cause human disease, including Type 2 diabetes.
Sequenom, Nussbaum, and NHGRI director Francis Collins formed a Cooperative Research Development Act agreement.
Bioinformatics is key to NHGRI’s investigation in two ways, Nussbaum explained. One is in the development of databases that contain the results of testing for these SNPs: "These databases are absolutely essential to be able to make any sense out of the data that you generate." NHGRI mines a database from the National Center for Biotechnology Information to find SNPs and then adapt them for its assays, he added.
Additionally, to determine whether DNA variations contribute to disease, researchers conduct statistical genetics analyses to detect higher frequencies of certain variations in individuals who have propensities to disease.
Sequenom has put together an automated platform for identifying SNP variations rapidly and accurately, said Nussbaum. The company has taken existing equipment and combined it into a stable system which, along with its software, makes it possible to test "genotypes quickly and capture them easily," he added. "They also have spent quite a bit of time developing molecular biology techniques to investigate how best to assay SNPs using mass spectrometry."
Besides learning more about the relationship between SNPs and disease, Nussbaum said NHGRI would like to make SNP detection cheaper and more rapid so that "ultimately, we can look at an extremely large number of SNPs in large numbers of people in a cost-effective and powerful way."
"The collaboration’s research goals are to develop and expand the use of matrix-assisted laser desorption and ionization mass spectroscopy, to use that for genotyping SNPs," Nussbaum told BioInform. Although there are many different technologies that can be used to study SNPs, Collins and Nussbaum decided that this approach was worth investigating because of the promise it appears to hold in automation, speed, and cost.
Sequenom describes its system as a novel approach to genotyping that combines the company’s proprietary enzymology and bioinformatics in a miniaturized chip-based format with mass spectrometry technology.
This achieves highly accurate results, said Toni Schuh, executive vice-president at Sequenom. An important difference between Sequenom’s and other gentoyping approaches is the company’s reliance on mass spectrometry for separation and detection.
"We therefore can work on label-free DNA and acquire the direct signal from the molecule," said Schuh. "Just about everybody else who does DNA analysis analyzes a tag--a fluorescent tag, a radioactive tag, or a mass tag.