SYDNEY: In the biggest contribution to genetics research since the Human Genome Project, scientists have compiled a comprehensive ‘parts list’ of the human genome.
The results have prompted a redefinition of the concept of a ‘gene’ and open up the ability to pinpoint genetic traits and diseases hidden in what was once considered ‘junk DNA’.
“This catalogue will serve as a basis for many biological and medical applications. It will ultimately be used to understand how the genome and the cells function,” said a lead researcher, Sarah Djebali, from the Centre for Genomic Regulation in Spain.
The Encyclopaedia of DNA Elements — or ENCODE — project has enabled scientists to assign specific biological functions to 80% of the human genome. The findings reveal that most of what was previously considered silent or ‘junk’ DNA is in fact more like a complex control panel responsible for switching genes ‘on’ and ‘off’.
“ENCODE tells us where the controls are”
“When the Human Genome Project was finished more than 10 years ago, we still didn't know what the vast majority of it meant,” Tim Reddy, from Duke University in North Carolina, said in a statement. Reddy was a lead analyst working on the ENCODE project.
“We knew back then where many of the genes were, but those genes only account for about 3% of the genome. ENCODE tells us where the controls are; it starts to fill in the 97% gap we had in our understanding,” he said.
ENCODE started in 2003 focussing on just 1% of the human genome, and moved to the entire genome in 2007. The project involved almost 500 scientists from 32 different labs around the world, and culminates this week with 30 publically available papers in the journals Nature, Science and Cell.
Boundaries between genes, and gene definition, blurred
The first draft of the human genome in 2001 described DNA as a string which contained genes in isolated sections that make up just 2% of its length. The space in between was dubbed ‘junk DNA’ and many researchers did not believe it served a function. Attention was focussed on the 'coding' genes that carried instructions for making the proteins that carried out basic biological functions.
However, among the new findings out of the ENCODE project, is that up to three-quarters of the human genome is capable of being transcribed — copied from DNA to RNA, which is the first step in gene expression — not just 2%.
The findings, published in Nature and co-authored by Djebali, challenge existing notions of what constitutes a gene and its boundaries on DNA.
"The boundaries of conventionally described genes are melding together, challenging the notion that a gene is a discrete, localised region of a genome separated by inert DNA," said another paper co-author Thomas Gingeras from Cold Springs Harbour Laboratory, New York, in a statement.
“New definitions of a gene are needed,” he said.
Answers for genetic traits and diseases
The new significance assigned to ‘junk DNA’ could hold the secret to pinpointing the genetic causes of a number of traits and diseases that previously eluded scientists.
"Genes occupy only a tiny fraction of the genome, and most efforts to map the genetic causes of disease were frustrated by signals that pointed away from genes," said John Stamatoyannopoulos, an ENCODE researcher at the University of Washington.
"Now we know that these efforts were not in vain, and that the signals were in fact pointing to the genome's 'operating system'," he said.
For instance, it took researchers decades to link a set of immune cells with the inflammatory bowel disease Crohn's. The ENCODE data was able to swiftly identify that the genetic variants associated with Crohn's were concentrated in that subset of cells.
Another ENCODE researcher, computer scientist Manolis Kellis, from the Massachusetts Institute of Technology in the U.S, said the next step was to "personalise" the findings. "To ask how they vary naturally between individuals, by profiling different cell types from different people, and how their variation relates to human disease and complex human traits," he said.
The research is funded by the U.S. National Human Genome Research Institute and has been made publically available to facilitate further research in the field.
