This surprising result comes from a study at the Wellcome Trust Sanger Institute of the activity of almost 14,000 genes in 270 DNA samples collected for the HapMap Project. The authors looked at 2.2 million DNA sequence variants (SNPs) to determine which affected gene activity.
They found that activity of more than 1300 genes was affected by DNA sequence changes in regions predicted to be involved in regulating gene activity, which often lie close to, but outside, the protein-coding regions.
"We predict that variants in regulatory regions make a greater contribution to complex disease than do variants that affect protein sequence," explained Dr Manolis Dermitzakis, senior author from the Wellcome Trust Sanger Institute. "This is the first study on this scale and these results are confirming our intuition about the nature of natural variation in complex traits.
"One of the challenges of large-scale studies that link a DNA variant to a disease is to determine how the variant causes the disease: our analysis will help to develop that understanding, a vital step on the path from genetics to improvements in healthcare."
Past studies of rare, monogenic disease, such as cystic fibrosis and sickle-cell anaemia, have focused on changes to the protein-coding regions of genes because they have been visible to the tools of human genetics. With the HapMap and large-scale research methods, researchers can inspect the role of regions that regulate activity of many thousands of genes.
The HapMap Project established cell cultures from participants from four populations as well as, for some samples, information from families, which can help to understand inheritance of genetic variation. The team used these resources to study gene activity in the cell cultures and tie that to DNA sequence variation
‘We have generated an information resource readily available to investigators working in the mapping of variants underlying complex traits. Regions of association can be correlated with signatures of regulatory regions affecting gene expression' explained Dr Panos Deloukas, Senior Investigator at the Wellcome Trust Sanger Institute
"We found strong evidence that SNP variation close to genes - where most regulatory regions lie - could have a dramatic effect on gene activity," said Dr Barbara Stranger, postdoctoral fellow at WT Sanger Institute. "Although many effects were shared among all four HapMap populations, we have also shown that a significant number were restricted to one population."
They also showed that genes required for the basic functions of the cell - so-called housekeeping genes - were less likely to be subject to genetic variation. "This was exactly as we would expect: you can't mess too much with the fundamental life processes and we predicted we would find reduced effects on these genes," said Dr Dermitzakis.
The study also detected SNP variants that affect the activity of genes located a great distance away. Genetic regulation in the human genome is complex and highly variable: a tool to detect such distant effects will expand the search for causative variants. The authors note, however, that the small sample size of 270 HapMap individuals is sensitive enough to detect only the strongest effects.
The results of this study are becoming available in public databases such as Ensembl for researchers to use.
The paper is accompanied by two others examining effects of changes to regulatory DNA in samples from asthma and from heart study patients.
Scientists discover species of dolphin that existed along South Carolina coast
24.08.2017 | New York Institute of Technology
The science of fluoride flipping
24.08.2017 | University of North Carolina Health Care
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
24.08.2017 | Medical Engineering
24.08.2017 | Earth Sciences
24.08.2017 | Earth Sciences