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In 1975, Sanger published his own DNA sequencing method alongside laboratory technician Alan Coulson, called the “plus and minus” technique. First, scientists mixed the DNA strand to be sequenced with an enzyme, DNA polymerase, as well as a primer, three normal dNTPs and one radiolabeled dNTP. Radiolabeled nucleotides are incorporated into growing DNA strands just like normal nucleotides, but are tagged with radioactive isotopes, such as phosphorus-32 or sulfur-35, so they can be detected using radiation-measuring equipment.
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