Public release date: 5-Sep-2012 [ | E-mail | Share ]

Contact: Jim Fessenden james.fessenden@umassmed.edu 508-856-2000 University of Massachusetts Medical School

WORCESTER, MA The first comprehensive decoding and annotation of the human genome is being published today by the ENCyclopedia Of DNA Elements (ENCODE) project, an international consortium of scientists from 32 institutions, including the University of Massachusetts Medical School. The groundbreaking ENCODE discovery appears in a set of 30 papers in Nature, Genome Research and Genome Biology.

Using data generated from 1,649 experiments with prominent contributions from the labs of UMMS professors Job Dekker and Zhiping Weng the group has assigned biochemical functions for an astounding 80 percent of the human genome. These findings promise to fundamentally change our understanding of how the tens of thousands of genes and hundreds of thousands of gene regulatory elements, or switches, contained in the human genome, interact in an overlapping regulatory network to determine human biology and disease.

As little as a decade ago, the human genome was viewed by scientists as a collection of independent genes that contained the instructions for making the proteins that carried out the basic biological functions necessary for life. Driven by this premise, most researchers focused on understanding the relatively small portion of the genome that made up protein-coding genes while the non-coding portion of the genome often referred to as "junk DNA" received little attention. The sequencing of the human genome in 2003 and more recent efforts by the ENCODE consortium, which is funded by the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH), and others over the last decade, has begun to fundamentally change researchers' views on the importance of the non-coding portion of the genome.

Scientists now know that the protein-coding portions of the genome make up only one part of our genetic picture. Of equal importance are those areas of the genome that regulate genes. These elements, such as regulatory DNA elements and non-coding RNA, control when a gene is turned on and off and can also amplify or curtail expression of a gene. Even a small change in when a gene is turned on can have a huge biological impact, or in specific circumstances, contribute to disease.

Taken together, genes and their regulatory elements create a vast network of overlapping systems that carry out the basic biological processes necessary for life, a system that scientists are only now beginning to understand. Using a wide variety of experimental and computational approaches, members of the ENCODE consortium have generated comprehensive information about the identities, locations and characteristics of human genes and regulatory switches throughout the genome. This data represents an expansive resource that biomedical researchers can use to begin unraveling how this system works and how it contributes to disease.

"This work provides a critical map of tens of thousands of genes and hundreds of thousands of regulatory switches that are scattered all over the 3 billion nucleotides of the genome," said Dr. Dekker, PhD, professor of biochemistry & molecular pharmacology and co-director of the Program in Systems Biology at UMMS. "As a group, we've identified more than 4 million sites that through binding specific proteins affect biological function."

Three dimensional wiring of the genome

What this map doesn't tell scientists, though, is which switches or elements regulate which genes. That is where the work of Dekker, the lead author on one of the six ENCODE papers that appear in Nature, provides unique insights. Over the last decade, Dekker has pioneered the development of chromosome conformation capture technologies (3C) and combined it with next-generation sequencing technologies (5C) to create three-dimensional models of folded chromosomes. In turn, these models can be used to determine which parts of the genome, when folded, come in physical contact.

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UMASS Medical School faculty annotate human genome for ENCODE project