Procedure to knock out genes in nematode discovered

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London, Apr 26 (ANI): After developing knockout mice and fruit flies, scientists have now devised a procedure for knocking out genes in nematode worms.

By knocking genes out of action, researchers led by biologist Erik Jorgensen University of Utah at, could learn what genes do by seeing what goes wrong without them.

"We developed a method that allows us to walk through the worm genome and determine the function of each gene, and thereby infer the function of these genes in humans," Nature quoted Jorgensen as saying.

The study shows how a transposon or "jumping gene" can be used to delete specific genes from the 1-millimeter-long nematode worm, Caenorhabditis elegans.

"We are trying to understand how genes work and are regulated, and the easiest way to do that is to use a simple organism. The amazing thing is that cellular processes in a lowly worm are similar to the biology in humans. We've made it much easier and faster to change the genetic blueprint of a simple worm so we can study and understand how genes are regulated," said Christian Frokjaer-Jensen, the study's first author.

Jorgensen added: "We want to know what human genes do because they allow us to do all the wonderful things we do - run, speak, live - and understand what goes wrong in genetic diseases and how we can possibly treat them."

"Mario figured out a way to delete genes in mice. 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," said Jorgensen.

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 added.

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 leave one chromosome and cutting DNA to insert themselves in another.

The Mos1 gene carries the code to make an enzyme named Mos1 transposase.

That enzyme does the actual cutting of DNA, said Frokjaer-Jensen.

The transposons in the new study came from fruit flies and were placed into the worm genetic blueprint by French scientists who provided them to the Utah team.

Frokjaer-Jensen said that the Utah researchers crippled the jumping genes put into worms "so we can control when and where they hop."

The Utah biologists used a plasmid - a circular piece of DNA - as a carrier by injecting it with the gene for Mos1 transposase, the "scissors" that cut DNA. Then, a glass needle was used to inject the combination into a worm's gonad.

The transposase-carrying plasmid then cuts out a Mos1 jumping gene adjacent to a gene that researchers want to knock out, leaving a break in the chromosome's DNA.

Cell machinery kicks in to repair the DNA break.

Since chromosomes come in pairs, the repair process normally uses the undamaged twin chromosome as a template for repairing the break.

But "in this case, we flood the cell with DNA that's similar to where the DNA was broken. We essentially trick the DNA machinery into repairing off a template we supply," said Frokjaer-Jensen.

But the template provided by the biologists lacks the DNA for the gene they want to delete. Thus, the gene is knocked out in the worm's offspring.

The study has been published in the journal Nature Methods. (ANI)

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