"We could eventually do direct detection of a DNA sequence from native DNA" without manipulation now performed in the laboratory, said Dr. Michael L. Metzker, assistant professor in the BCM Human Genome Sequencing Center and adjunct assistant professor of chemistry at Rice. "We could make sequencing portable and do it faster."
The research appears this week in the journal Proceedings of the National Academy of Sciences. In the paper, Metzker, Rice University Professor Robert Curl and colleagues from BCM and Rice describe a new way of doing DNA sequencing that could be more accurate than current methods.
DNA in the nucleus of every human cell is made of long chains of building blocks called nucleotides. DNA is made up of just four types of nucleotides referred to as A, C, G and T and is organized in such a way that A binds T and G binds C, forming a double helical structure. Each person's genome consists of a unique ordering of some 3 billion base pairs, and 'DNA sequencing' refers to the process scientists use to read out the order of those nucleotides.
In sequencing, scientists first extract DNA from the nuclei of cells and through a painstaking series of bacterial cloning and/or polymerase chain reaction (PCR) steps, reduce its length to a manageable size of thousands of nucleotides. Using natural replicating enzymes, the DNA is tagged with four fluorescent dyes, each corresponding to a particular nucleotide. This tagging process, called Sanger sequencing, results in smaller DNA fragments, which are then separated base-by-base. Because the DNA fragments are tagged with dyes, they glow when they are struck by laser light to determine t