Fish Lend Insight into Human DNA

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Scientists at the Lawrence Berkeley Laboratory have embarked upon a new endeavor to sequence the genome of a Japanese pufferfish - an undertaking that will help decipher the recently completed map of the human genome and provide insight into how specific human genes function.

Researchers from the Lawrence Berkeley Laboratory, along with a team of scientists from around the world, launched the Fugu genome project in an effort to help scientists understand genes from the humane genome data.

"The Fugu genome fits into the Human Genome Project because one of the great feats of science and biology is to try to figure out where the human genes are in the genome and where the control regions of those genomes actually are," said Trevor Hawkins, deputy director of the Joint Genome Institute of the U.S. Department of Energy.

Hawkins, who developed the international consortium, said the team hopes to finish sequencing the genome of Fugu rebripes, the pufferfish, by March of next year.

Finding the genes and controlling sequences through the pufferfish model makes understanding the roles of genes an easier task because the Fugu genome contains just three billion bases, compared to the four hundred billion bases that make up human DNA.

The pufferfish, which is often served as a Japanese delicacy, has a smaller number of base pairs in its genome, which helps scientists immensely because it eliminates the hundreds of billions of pairs considered "junk" DNA in the genome that do not code for any function.

"Only three to five percent of the human genome actually encodes genes," Hawkins said. "That means that only ninety-five percent of the genome does virtually nothing."

The remaining DNA sequences from the pufferfish would have similar function to human DNA sequences.

"Evolution tends to keep a good thing," Hawkins said. "It doesn't fix what isn't broken."

The sequencing project is part of an effort to identify the location of human genes within the human genome. Scientists are studying organisms with genome sequences that diverge from humans and using those sequences to learn about human beings.

"You can't do experiments with humans, so you need models," said Lee Rowen, who works alongside members of the consortium at the Institute for Systems Biology. "There are a number of model organisms being sequenced such as yeast, fruit flies and worms."

Researchers plan to use comparisons between the Fugu genome and the existing mouse genome project to provide the scientific world with critical information about the human genome.

"The Fugu genome project is important because although there is a risk, we will learn more by looking at the Fugu sequence," Rowen said. "The Fugu genome will provide us with more tools to work with, enabling us to gain more knowledge about the human genome."

With the sequencing of the mouse, Fugu, and human genome, scientists will have a greater likelihood of locating the position of genes.

"The more data points you can collect, the easier it is to pinpoint common elements between three different species, and the more likely you are to pinpoint where genes and the control regions are located," Hawkins said. "If you take the human, mouse and Fugu genetic sequences and layer them on top of each other, there are regions that are different but there will also be regions that are very similar because they encode genes. These regions are the control regions."

Rowen suggested that the Fugu genome project will enable researchers to identify what drugs will work better for different people with different genes.

"Different people have different side effects to drugs," he said. "The new discovery of genes can help us understand why different people have different side effects to drugs and will help tell us what drugs will work best with what people."

The pufferfish is a more cost-efficient model that is significantly better than other organisms because it is more closely related to humans than the previous models, Rowen said.

"The Fugu genome will provide an additional model system to understand the basic biology of human cell development," he said.

Rowen stressed the importance of the Fugu project in providing new genomic data that will generate a greater understanding about genes.

"By understanding what genes are, what they do, and how they vary between individuals by identifying what variations in sequences exists between species, we will be able to see how various genes function," Rowen said.

Although Hawkins acknowledges that it is difficult to quantify the real effects of sequencing the Fugu genome, he said he remains confident that the project will create immense benefits, such as the ability to find diseased genes.

"One will be able to use the genes found in the mouse and compare that to human genes," Hawkins said. "People will be able to find particular diseases caused by genes in the mouse and relate that to humans."

The Human Genome Project was initiated in 1986 after Congress mandated a study of the genetic and health effects of radiation and chemical by-products of energy production, according to the Lawrence Berkeley National Laboratory.

Hawkins is currently working in collaboration with Fugu genome project creator Sydney Brenner and other scientists from around the world. The project has benefited immeasurably with the inclusion of international laboratories have been indispensable to the genome project.

"The laboratories in Singapore and the other countries are invaluable resources for the project with their clones and knowledge about the kinds of sequences that have already been produced," Hawkins said.

The international team said they plan to have a draft of the Fugu genome project by March of next year and a high draft of the project by April or May.

Hawkins remains confident that although the Fugu genome project is only the starting point to a long process of gene delineation, the project will have a significant effect in the scientific field.

"There will be a very tremendous impact from sequencing the Fugu genome," Hawkins said.


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