Multidisciplinary Collaborations Lead to Successful Genetic Research

Steps in positional cloning. Positioning of disease loci to chromosomal regions requires multidisciplinary collaborations. "You have a clinician out in Israel gathering patients, a medical geneticist doing genetic mapping, my lab doing physical mapping, and Washington University sequencing. All these things come together and, boom, in record time you have this gene," says Green. Green goes on to point out that this is a classic example of finding a gene from sequences the Human Genome P

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Green goes on to point out that this is a classic example of finding a gene from sequences the Human Genome Project is posting on the World Wide Web every night (www.nhgri.nih.gov/Data/#mapping). Other groups trying to find PDS were looking at the Washington University sequence as well.3 "It was a horse race. We competed to the end," says Green.

"We spent several months trying to manipulate the system in various ways to demonstrate sulfate transport. After getting negative results, it finally dawned on us that maybe we should be looking for other possible anions the protein could transport," says Karniski. Iodide, given pendrin's high expression in the thyroid, and chloride, due to its structural similarity to iodide, were logical candidates.

Karniski showed pendrin actually transports chloride and iodide ions, and not sulfate as previously assumed.4 This demonstrates the need to be careful about homology searches. Karniski warns, "Just because proteins ...

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