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In addition to DNA sequencing and mapping methods, a broad spectrum of laboratory methods for manipulating DNA were crucial in the run-up to the sequencing of the human genome. The discovery of restriction enzymes allowed for the manipulation of genes and the ability to stitch genes of interest into cloning vectors. Restriction enzyme cleavage of patient DNA was the pre-requisite to performing linkage analysis; radioactively labeled DNA probes were hybridized to cleaved DNA separated on an agarose gel and transferred to a nitrocellulose membrane using the Southern blot, named after Ed Southern. (The corresponding method for RNA was dubbed the Northern blot). These methods also paved the way for the discovery of DNA fingerprinting, with the focus on inheritance of repetitive DNA fragments rather than single genes. Perhaps the most important lab method was the DNA amplification method called polymerase chain reaction (PCR), developed by Kary Mullis and colleagues in the mid- 1990s.

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