"Mario figured out a way to delete genes in mice," Jorgensen says. "Golic figured out how to do it in fruit flies. And we figured out how to delete genes in worms. There is an institutional excellence in genetics at the University of Utah."
A Genetic Knife Rather than a Hand Grenade
Genes are on long strands of DNA known as chromosomes. Until now, the main way of altering nematode genes was by using chemicals to induce mutations randomly. The method cannot specify how much DNA should be deleted or exactly where.
"It's like throwing a hand grenade at the genome [genetic blueprint]," Jorgensen says. "Our method is like a surgeon perfectly cutting out a gene."
He says random mutation doesn't always cripple an entire gene, but just part of it, and can perturb other genes, making it difficult to determine what the targeted gene does.
Random mutagenesis has been able to delete only 5,003 of the 20,160 genes in nematode worms, Jorgensen says. Scientists want to knock out almost all nematode worm genes because "many of the genes in worms are the same as in humans. If we are to understand human genes, it's easier to understand their function in a worm."
The method developed by Capecchi can hit every gene in mice, crippling them but usually not completely deleting them entirely because mouse genes are large, Jorgensen says. In nematode worms, "we're knocking out the entire gene, but we cannot knock out every individual gene in the worm yet," although the method should be able to delete 20,043 of 20,160 nematode genes, or 99.4 percent, he adds.
Exploiting a Cell's DNA Repair Mechanism
The new knockout method is named MosDel for Mos-mediated deletion because it involves a transposon or jumping gene named Mos1. Jumping genes are pieces of DNA that can jump from one chromosome to another, cutting the DNA where they le
|Contact: Lee Siegel|
University of Utah