Featured Research

from universities, journals, and other organizations

Biochemical functions for most of human genome identified: New map finds genetic regulatory elements account for 80 percent of our DNA

Date:
September 5, 2012
Source:
Massachusetts Institute of Technology
Summary:
Only about 1 percent of the human genome contains gene regions that code for proteins, raising the question of what the rest of the DNA is doing. Scientists have now begun to discover the answer: About 80 percent of the genome is biochemically active, and likely involved in regulating the expression of nearby genes, according to a study from a large international team of researchers.

Only about 1 percent of the human genome contains gene regions that code for proteins, raising the question of what the rest of the DNA is doing. Scientists have now begun to discover the answer: About 80 percent of the genome is biochemically active, and likely involved in regulating the expression of nearby genes, according to a study from a large international team of researchers.

Related Articles


The consortium, known as ENCODE (which stands for "Encyclopedia of DNA Elements"), includes hundreds of scientists from several dozen labs around the world. Using genetic sequencing data from 140 types of cells, the researchers were able to identify thousands of DNA regions that help fine-tune genes' activity and influence which genes are expressed in different kinds of cells.

Just as the sequencing of the human genome helped scientists learn how mutations in protein-coding genes can lead to disease, the new map of noncoding regions should provide some answers on how mutations in the regulatory elements lead to diseases such as lupus and diabetes, says Manolis Kellis, an associate professor of computer science at MIT, an associate member of the Broad Institute and an author of a paper describing the findings in the Sept. 5 online edition of Nature.

"Humans are 99.9 percent identical to each other, and you only have one difference in every 300 to 1,000 nucleotides," Kellis says. "What ENCODE allows you to do is provide an annotation of what each nucleotide of the genome does, so that when it's mutated, we can make some predictions about the consequences of the mutation."

Kellis, who leads MIT's Computational Biology Group, is one of the principal investigators involved in the Nature paper. The ENCODE collaboration is publishing about two dozen additional papers this week detailing the new results.

Mapping noncoding DNA

ENCODE was established in 2003 to extend our understanding of the human genome beyond protein-coding genes. One way to do that is by studying the chemical modifications of individual stretches of DNA, which control when genetic regions will be active. These modifications vary by cell type and can modify either DNA directly or the histone proteins that DNA wraps around.

To map these modifications, known collectively as the epigenome, the research groups had to collect many different kinds of data from different cell types. Some labs measured DNA or histone modifications, while others gauged the accessibility of different stretches of DNA by cutting it into fragments with enzymes.

Kellis and his group were among the computational scientists leading the effort to analyze and integrate the huge amount of data generated by different labs. "Given that we were getting more than 1,000 data sets, we had to figure out ways to automatically calibrate experiments," says Anshul Kundaje, a research scientist in MIT's Computational Biology Group. "We developed an almost purely automated system that did all of this."

The ENCODE researchers found that 80 percent of the genome experiences some kind of biochemical event, such as binding to proteins that regulate how often a neighboring gene is utilized. They also discovered that the same regulatory region can play different roles, depending on what type of cell it's acting in.

The findings should have a major impact on scientists' understanding of human biology and how genomic variations can cause disease, says Ben Raphael, an associate professor of computer science at Brown University.

"The most exciting part is now we're getting a whole genome annotation of functional elements," says Raphael, who was not part of the research team. "Every time you want to understand what a particular piece of the genome is doing, you can use the data from this project."

Human variation

The researchers also studied the conservation of nucleotides -- the A, T, C and G "letters" of DNA -- in the newly identified regulatory regions. Nucleotides are conserved if they remain the same over long evolutionary periods, which can be measured by analyzing the variability between species, or among individuals within a species.

A recent paper by Kellis and colleagues showed that 5 percent of noncoding DNA is conserved across mammals. In one of the ENCODE companion papers appearing online Sept. 5 in Science, Kellis and MIT postdoc Lucas Ward show that an additional 4 percent is conserved within the human lineage, suggesting that those elements control recently evolved traits, some of which are unique to humans.

When the researchers looked at the functions of genes near newly evolved regulatory regions, they found many genes that encode regulators that activate other genes. "Genes involved in the nerve growth pathway and color vision, both of which have been hypothesized to be recent innovations in the primate lineage, are enriched in human-constrained elements in non-conserved regions," Ward says.

The researchers found that the most highly conserved nucleotides were also the ones most likely to be associated with disease when mutated. They also showed that variants associated with autoimmune diseases such as lupus and rheumatoid arthritis are located in regions active only in immune cells, while variants linked to metabolic diseases are in regions active only in liver cells.

In their next phase, the ENCODE researchers hope to determine just how those variations lead to human disease.

"What we've done over this series of papers is effectively paint a set of reference annotations of common human genome function," Kellis says. "Our next steps will be to personalize these maps -- to basically 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."

In one follow-up project, Kellis and colleagues are comparing activity levels of regulatory elements in different cell types from the same person, across many individuals. Another project is looking at DNA modification patterns across the entire genome of many individuals, in hopes of identifying how variation of specific elements relates to disease.

The research was funded by the National Human Genome Research Institute.


Story Source:

The above story is based on materials provided by Massachusetts Institute of Technology. The original article was written by Anne Trafton, MIT News Office. Note: Materials may be edited for content and length.


Cite This Page:

Massachusetts Institute of Technology. "Biochemical functions for most of human genome identified: New map finds genetic regulatory elements account for 80 percent of our DNA." ScienceDaily. ScienceDaily, 5 September 2012. <www.sciencedaily.com/releases/2012/09/120905154823.htm>.
Massachusetts Institute of Technology. (2012, September 5). Biochemical functions for most of human genome identified: New map finds genetic regulatory elements account for 80 percent of our DNA. ScienceDaily. Retrieved January 30, 2015 from www.sciencedaily.com/releases/2012/09/120905154823.htm
Massachusetts Institute of Technology. "Biochemical functions for most of human genome identified: New map finds genetic regulatory elements account for 80 percent of our DNA." ScienceDaily. www.sciencedaily.com/releases/2012/09/120905154823.htm (accessed January 30, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, January 30, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Oxfam Calls for Massive Aid for Ebola-Hit West Africa

Oxfam Calls for Massive Aid for Ebola-Hit West Africa

AFP (Jan. 29, 2015) Oxfam International has called for a multi-million dollar post-Ebola "Marshall Plan", with financial support given by wealthy countries, to help Guinea, Sierra Leone and Liberia to recover. Duration: 01:10 Video provided by AFP
Powered by NewsLook.com
Are We Winning The Fight Against Ebola?

Are We Winning The Fight Against Ebola?

Newsy (Jan. 29, 2015) The World Health Organization announced the fight against Ebola has entered its second phase as the number of cases per week has steadily dropped. Video provided by Newsy
Powered by NewsLook.com
Calif. Health Officials Campaign Against E-Cigarettes

Calif. Health Officials Campaign Against E-Cigarettes

Newsy (Jan. 29, 2015) The California Health Department says e-cigarettes are a public health risk for both smokers and those who inhale e-cig smoke secondhand. Video provided by Newsy
Powered by NewsLook.com
Measles Scare Sends 66 Calif. Students Home

Measles Scare Sends 66 Calif. Students Home

AP (Jan. 29, 2015) Officials say 66 students at a Southern California high school have been told to stay home through the end of next week because they may have been exposed to measles and are not vaccinated. (Jan. 29) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

More Coverage


Human Genome Far More Active Than Thought: GENCODE Consortium Discovers Far More Genes Than Previously Thought

Sep. 5, 2012 The GENCODE Consortium expects the human genome has twice as many genes than previously thought, many of which might have a role in cellular control and could be important in human disease. This ... read more

Comprehensive Transcriptome Analysis of Human ENCODE Cells

Sep. 5, 2012 ENCODE, an international research project led by the National Human Genome Research Institute (NHGRI), has produced and analyzed 1649 data sets designed to annotate functional elements of the entire ... read more

Fast Forward for Biomedical Research: Massive DNA Encyclopedia Scraps the Junk

Sep. 5, 2012 Today, an international team of researchers reveal that much of what has been called 'junk DNA' in the human genome is actually a massive control panel with millions of switches regulating ... read more

Huge Human Gene Study Includes Penn State University Research

Sep. 5, 2012 The first integrated understanding of how the human genome functions will be published this week -- the triumphant result of a collaborative five-year project called ENCODE, involving more than 440 ... read more

UMASS Medical School Faculty Annotate Human Genome for ENCODE Project

Sep. 5, 2012 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 ... read more

UC Santa Cruz Provides Access to Encyclopedia of the Human Genome

Sep. 5, 2012 The ENCODE project has enabled scientists to assign specific functions for 80 percent of the human genome, providing new insights into the mechanisms of gene regulation and giving biomedical ... read more

Yale Team Finds Order Amidst the Chaos Within the Human Genome

Sep. 5, 2012 The massive Encyclopedia of DNA Elements (ENCODE) unveiled Sept. 5 reveals a human genome vastly more rich and complex than envisioned even a decade ago. In a key supporting paper published in the ... read more

First Holistic View of How Human Genome Actually Works: ENCODE Study Produces Massive Data Set

Sep. 5, 2012 The Human Genome Project produced an almost complete order of the 3 billion pairs of chemical letters in the DNA that embodies the human genetic code -- but little about the way this blueprint works. ... read more

Allegedly Useless Parts of the Human Genome Fulfil Regulatory Tasks

Sep. 7, 2012 Heidelberg scientists contribute to the encyclopedia of all functional DNA elements in the human ... read more

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins