In October 2000, a collaboration of American, Japanese, German, and Swedish researchers accomplished a major first: They positionally cloned the gene associated with a common polygenic disorder, namely, type 2 diabetes or non-insulin-dependent diabetes mellitus (NIDDM).1 Despite this Hot Paper's importance, researchers continue to dispute the significance of the gene across multiple ethnic populations. The intricacies of the positional cloning process and the investigators' seemingly unlikely culprit gene have generated skepticism from many.
As senior author Graeme Bell explains, positional cloning is difficult because the targeted genome regions are not as precisely defined by recombination events as they are with monogenic disorders. Instead, the gene's location is defined statistically. "We worked in a region where we thought we had a 95% chance of finding it," says Bell, a Howard Hughes Medical Institute investigator and professor of molecular biology and biochemistry at the University of Chicago. "There was a 5% chance ...
