This discovery of the extent of genetic variation, by Howard Hughes Medical Institute (HHMI) international research scholar Stephen W. Scherer, and colleagues, is expected to change the way researchers think about genetic diseases and human evolution.
Genes usually occur in two copies, one inherited from each parent. Scherer and colleagues found approximately 2,900 genes--more than 10 percent of the genes in the human genome--with variations in the number of copies of specific DNA segments. These differences in copy number can influence gene activity and ultimately an organism's function.
To get a better picture of exactly how important this type of variation is for human evolution and disease, Scherer's team compared DNA from 270 people with Asian, African, or European ancestry that had been compiled in the HapMap collection and previously used to map the single nucleotide changes in the human genome. Scherer's team mapped the number of duplicated or deleted genes, which they call copy number variations (CNVs). They reported their findings in the November 23, 2006, issue of the journal Nature.
Scherer, a geneticist at the Hospital for Sick Children and the University of Toronto, and colleagues searched for CNVs using microarray-based genome scanning techniques capable of finding changes at least 1,000 bases (nucleotides) long. A base, or nucleotide, is the fundamental building block of DNA. They found an average of 70 CNVs averaging 250,000 nucleotides in size in each DNA sample. In all, the group identified 1,447 different CNVs that collectively covered about 12 percent of the human genome and six to 19 percent of any given chromosome--far more widespread than previously thought.
Not only were the changes common, they also were large. "We'd find missing pieces of DNA, some a million or so nucleotides long," Scherer said. "We used to think that if you had big changes like this, then they must be involved in disease. But we are showing that we can all have these changes."
The group found nearly 16 percent of known disease-related genes in the CNVs, including genes involved in rare genetic disorders such as DiGeorge, Angelman, Williams-Beuren, and Prader-Willi syndromes, as well as those linked with schizophrenia, cataracts, spinal muscular atrophy, and atherosclerosis.
In related research published November 23, 2006, in an advance online publication in Nature Genetics, Scherer and colleagues also compared the two human genome maps--one assembled by Celera Genomics, Inc., and one from the public Human Genome Project. They found thousands of differences.
"Other people have [compared the two human genome sequences]," Scherer said, "but they found so many differences that they mostly attributed the results to error. They couldn't believe the alterations they found might be variants between the sources of DNA being analyzed."
A lot of the differences are indeed real, and they raise a red flag, he said.
Personalized genome sequencing--for individualized diagnosis, treatment, and prevention of disease--is not far off, Scherer pointed out. "The idea [behind comparing the human genome sequences] was to come up with a good understanding of what we're going to get when we do [personalized sequencing]," he explained. "This paper helps us think about how complex it will be."
In a "News and Views" article in the same issue of Nature, HHMI professor Huntington F. Willard writes, "the stage is set for global studies to explore anew…the clinical significance of human variation." Willard is director of the Institute for Genome and Science Policy at Duke University.
To fully extract meaningful data using the human genome maps, researchers must know what's missing and how much variation exists, Scherer said. "Our computer algorithms are smart, but it is hard to find something if it is not there in the reference you are comparing against."
In fact, Scherer's group found some 30 million nucleotides that are seemingly not yet represented at all, or in different copy numbers or orientations, when comparing the Celera assembly to the public human genome sequence. The entire human genome is thought to contain about 3 billion nucleotides.
The discovery of an abundance of DNA variation puts a whole new spin on the study of genetic disease. Most research has focused on small alterations, called single nucleotide polymorphisms (SNPs). It may be, said Scherer, that some diseases are caused by copy number variations rather than SNPs. In fact, recent research has already linked such variations to kidney disease, Parkinson's disease, Alzheimer's disease, and AIDS susceptibility.
The discovery also provides a new outlook on evolution.
"Until now, our focus has been on examining evolution through either small SNP changes or larger chromosomal alterations you can see under the microscope, because that's what we could detect," Scherer said. "But now there's a whole new class of mid-sized variants encompassing millions of nucleotides of DNA to consider."
This change in the way scientists think about human genetics is exciting, but it is still very early to know what all this means, said Scherer. "Though it does make you wonder, he added. "If you have 1 million fewer nucleotides than your buddy, shouldn't you get a break on your golf handicap?"
Jennifer Donovan | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy