Washington: The massive Encyclopaedia of DNA Elements (ENCODE) reveals a human genome infinitely richer and more complex than envisioned even a decade ago, including how much of mom and dad are genetically active in each of us.
The lab of Mark Gerstein, professor of biomedical informatics at Yale University, has found order amid the seeming chaos of trillions of potential molecular interactions. Scientists show it is not just the gene, but the network that makes the human genome dynamic.
"We now have a parts list of what makes us human. What we are doing is figuring out the wiring diagram of how it all works," Gerstein said of the ENCODE, unveiled on Wednesday," according to the journal Nature.
What Gerstein has found is a regulatory network that has properties similar to, say, the connections in a social network or the organisational chart of a Fortune 500 company, according to an Yale statement.
Yale researchers say they can now tell how much "mom" and how much "dad" is genetically active in each of us.
These gender-specific markers may not determine which parent can take credit —or the blame— for the successes or shortcomings of their offspring. However, they could help explain differences in human populations.
Using sophisticated math modelling, his team traced the cascade of a half million molecular interactions triggered by 119 transcription factors — special genes that can simultaneously activate or silence thousands of genes.
The model shows that these transcription factors are wired together in a hierarchical fashion, with some factors operating like top-level executives, and some as middle managers or shop foremen.
Together they regulate the 20,000 or so genes in the human genome.
However, the "executive-level" transcription factors do tend to have the most influence in key functions such as driving gene expression, and also have better connections with other genes in different molecular networks.
Attesting to their importance to survival, these "executives" tend to be more conserved across populations.
The ENCODE project shows dramatically that there are hundreds of thousands of more distant elements, known as enhancers, that can influence human gene action from afar.
Gerstein's team found that networks regulated by enhancers tend to be wired differently than those regulated by nearby promoters.
"This wiring diagram gives us framework to interpret the many variants of personal genomes that don't directly affect genes," Gerstein said.
Key Yale contributors to this research include Koon-Kiu Yan, Chao Cheng, Xinmeng Jasmine Mu, Ekta Khurana, Joel Rozowsky, Roger Alexander, and Sherman Weissman. The work was funded by the National Human Genome Research Institute, US.
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