Scientists map all mammalian gene interactions

Aug 09, 2010
This map of subnetwork centered around the gene cyclooxygenase-1 (COX1 or PTGS1) involved in synthesis of prostaglandins, which control smooth muscle activity in the body along with many other physiological functions. Credit: UCLA

In one of the first efforts of its kind, UCLA researchers have taken mammalian genome maps, including human maps, one step further by showing not just the order in which genes fall in the genome but which genes actually interact.

The findings, published in the August issue of the journal Genome Research, will help researchers better understand which work together and shed light on how they collaborate to help cells thrive or die.

Mammals, including humans, have roughly 20,000 different genes. Genes hold instructions to create proteins that determine not only physical characteristics, like outward appearance, but all bodily processes, from moving blood through the veins to stimulating the immune system to attack a cold virus. They can also be pivotal in the development of diseases like cancer.

Each mammalian cell contains the full complement of genes, although depending on the activity of the cell, not all the genes are active. The genes engage not only in one-on-one interactions but also create wide networks involving dozens of genes. Little had previously been known about which genes work together most often in mammals and the networks they form.

For this study, the UCLA scientists used human radiation hybrid genome maps developed several years ago for the worldwide , as well as several other mammalian radiation hybrid maps, for dogs, cats and mice.

They found substantial overlap and commonalities between gene interactions and networks across all four species, thus creating the first complete and comprehensive genetic interaction maps for mammalian cells.

Previous research had mapped interactions between proteins, which are set in motion by genes, but not the genes themselves, which provide more direct and nearly comprehensive
information about the connection strength between genes. Researchers say this is an important step in furthering the understanding of the role each gene plays in triggering a process or function in the body.

"We were surprised that no one had done this before and that it worked so well," said study author Desmond Smith, a professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA. "Modern genome science, although still in its infancy, has accumulated enormous amounts of information that can be repurposed to produce findings such as ours for decades to come. We've just scratched the surface."

To explore the gene interactions, the scientists statistically tested how often one gene appeared with another gene in a cell and which ones appeared together most often.

They determined that genes that frequently appear simultaneously in the radiation hybrid cells, even though they reside far apart on the genome, must be coming together for biological interactions. They found a network of more than 7 million interactions encompassing essentially every one of the genes in the mammalian genome.

The new findings go beyond just understanding where a gene is located, based on DNA sequencing — that is, the order in which they reside in a cell.

"Current genetic maps show the order of genes and where they physically reside, like a street map of homes," Smith said. "We took it one step further and were able to map which genes interact when they leave their homes and go to work."

"By looking at a gene's network of 'friends and co-workers,' we can tell a lot about its role and purpose," said study author Andy Lin, a postdoctoral researcher in the UCLA Department of Molecular and Medical Pharmacology. "Mapping gene interactions is useful for both basic science and clinical research."

According to the researchers, some genes were found to have more extensive interactions than others, which may be helpful in finding specific drug targets to fight diseases such as cancer.

Smith compared the gene networks involved in promoting disease to the criminal world.

"The most well-connected gene represents someone powerful, like Al Capone, surrounded by his gang of mobsters. If we don't have a drug to target this main gene, there may be an existing drug that will effectively knock out a second-in-command, launching a flank attack that would cripple the primary gene's actions."

The findings, the researchers said, will help researchers in the field.

"The UCLA interaction map is a significant one that will help broaden the understanding of the working relationships between genes," said Tara C. Matise, an associate professor in the department of genetics at Rutgers University and director of the Laboratory of Computational Genetics, who was not part of the study. "The more information we acquire about genetic interactions, the more effective scientists can be in developing bench-to-bedside research."

Now that the researchers have mapped these interactions, the next step is to conduct biological experiments to further understand these interactions and how the genes work together.

Explore further: Stress reaction may be in your dad's DNA, study finds

Provided by University of California - Los Angeles

4.7 /5 (7 votes)

Related Stories

Genetic 'atlas' of cells will pinpoint causes of disease

Jan 25, 2010

(PhysOrg.com) -- Scientists at the University of Toronto have discovered a way to map the interactions of genes within a cell, a significant breakthrough that promises to help researchers better understand the causes of disease, ...

Location matters, even for genes

Feb 13, 2008

Moving an active gene from the interior of the nucleus to its periphery can inactivate that gene report scientists from the University of Chicago Medical Center in an article to be published early online Feb.13, 2008, in ...

Connecting cancer genes

May 15, 2008

A large genetic study in mice has identified hundreds of genes involved in the development of cancer by examining the DNA of more than 500 lymphomas to find the cancer causing mutations.

Researchers map 'gene switches' within the human genome

Apr 10, 2006

Researchers have released a "map" of regions in the human genome that work as "switches" for turning genes on and off. The discovery, made by researchers from McGill University, the Institut de recherches cliniques de Montréal ...

Recommended for you

Stress reaction may be in your dad's DNA, study finds

Nov 21, 2014

Stress in this generation could mean resilience in the next, a new study suggests. Male mice subjected to unpredictable stressors produced offspring that showed more flexible coping strategies when under ...

More genetic clues found in a severe food allergy

Nov 21, 2014

Scientists have identified four new genes associated with the severe food allergy eosinophilic esophagitis (EoE). Because the genes appear to have roles in other allergic diseases and in inflammation, the ...

Brain-dwelling worm in UK man's head sequenced

Nov 20, 2014

For the first time, the genome of a rarely seen tapeworm has been sequenced. The genetic information of this invasive parasite, which lived for four years in a UK resident's brain, offers new opportunities ...

User comments : 2

Adjust slider to filter visible comments by rank

Display comments: newest first

TAz00
not rated yet Aug 10, 2010
Someone! make this into a coding language
Palli
not rated yet Aug 10, 2010
Someone! make this into a coding language

Please don't let it be google!

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.