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Human variation revealed

Scientists have generated the most comprehensive map of the structural variation that exists among normal, healthy humans, according to a study published online today in Nature. Understanding normal variation between individuals is critical to identifying abnormal changes that may contribute to a wide variety of heritable diseases. Image: Wikimedia commons"I think it's considered to be a landmark paper," said geneticist linkurl:Frank Speleman;http://users.ugent.be/%7Efspelema/neubla/nb.htm of t

By | October 7, 2009

Scientists have generated the most comprehensive map of the structural variation that exists among normal, healthy humans, according to a study published online today in Nature. Understanding normal variation between individuals is critical to identifying abnormal changes that may contribute to a wide variety of heritable diseases.
Image: Wikimedia commons
"I think it's considered to be a landmark paper," said geneticist linkurl:Frank Speleman;http://users.ugent.be/%7Efspelema/neubla/nb.htm of the Center for Medical Genetics at Ghent University Hospital in Belgium, who was not involved in the work. "It's quite important in the complete context of genome wide association studies and genetic predisposition." Using microarrays that contained more than 42 million probes, genome scientist linkurl:Stephen Scherer;http://www.tcag.ca/scherer/ of The Hospital for Sick Children in Toronto and the University of Toronto and his colleagues searched the genome of 40 healthy individuals for copy number variants (CNVs) -- areas of the genome that come in varying quantities as a result of deletions, insertions, or duplications. The researchers identified 11,700 CNVs 443 base pairs or greater in size, with an average of approximately 1,000 CNVs differing between any two individuals. "[That's] an important amount of normal variation that happens in the genome," Speleman said. The team then genotyped more than 5,000 of the CNVs from 450 individual genomes pulled from the International HapMap project to determine the population frequency and distribution of these variable regions. This generated a database of normal variation that can be correlated to specific populations and examined for patterns of inheritance among related individuals. "There is this paradigm shift that CNVs are being incorporated into genetic studies," Scherer said. "And I think it's going to enlighten a lot of our interpretations" of genome wide association studies and other human genetics research. Scherer and his colleagues generated a similar map in 2006 which, "while comprehensive," Scherer said, "was pretty low resolution." At that time, the researchers could only confidently detect CNVs of 50 kilobases or more. "We had no real idea of what the characteristics looked like," Scherer said. "Some of the CNVs were in fact overlapping with other CNVs and we couldn't really tell what was what." Now, just three years later, they've upped their resolution by two orders of magnitude -- a goal coauthor linkurl:Matthew Hurles;http://www.sanger.ac.uk/Teams/Team29/ linkurl:quoted to The Scientist;http://www.the-scientist.com/news/display/36731/ after publishing the first map. With this higher resolution technology, the researchers believe they have documented about 70% of the common CNVs (those that occur in more than 5% of the population). The CNVs they identified, however, failed to explain the high heritability of many complex diseases. The contributing factors, Scherer suggested, are likely to be the rare CNVs, which are more difficult to identify. While the results of this study clearly fill in some important detail to the map of human CNVs, there are still many CNVs left to be discovered, the authors admit. "I'm excited by the fact that they've finally released this data," said human geneticist linkurl:Evan Eichler;http://eichlerlab.gs.washington.edu/ of the University of Washington. "[But] I think this is far from being comprehensive at this point." The next step, he said, is sequencing individual genomes with long reading frames to further increase the resolution. "You're only as good as you can genotype," he said. The study "tells us something about the frequency of CNVs and sheds a little bit of light on their role in common disease," said molecular biologist linkurl:George Zogopoulos;http://www.mshri.on.ca/gallinger/aboutthelab.htm of the University of Toronto, who also did not participate in the research. "[Now] we need to look at diseased genomes." Comparing the genomes of individuals affected by certain diseases to healthy controls may identify important CNV-disease associations, he explained. Despite all that remains to be done, this study -- along with other ongoing efforts to further characterize the human genome -- have added tremendously to our understanding of human genetics, Speleman said. "In the past years, an enormous leap has been taken. We're looking at huge amounts of information, which are generating a lot of new views on the variability of the genome."
**__Related stories:__***linkurl:Genomic Alterations 2.0;http://www.the-scientist.com/article/display/53607/
[October 2007]* linkurl:Tips for CNV Detection;http://www.the-scientist.com/article/display/53644/
[October 2007]*linkurl:Structural variations common in human genome;http://www.the-scientist.com/news/display/36731/
[22nd November 2006]
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Comments

Avatar of: Dov Henis

Dov Henis

Posts: 97

October 8, 2009

Science Blindness To Gene's Lifehood\n\n\nA. From "Better sensing through empty receptors"\n\nhttp://tinyurl.com/y9fxnks\n\nA new model suggests cells may be more sensitive to their environment than previously thought.\n\nThis work deals with the mechanism and efficiency of some components of the sensing system on a monocell organism's outer membrane. It refers to\n\n- cells may benefit...\n- how a cell sorts information...\n- single-celled organisms, such as bacteria and yeast, must accurately judge their landscape to find food and avoid trouble.\n\n\nB. From "Bacterium With Chemoreceptors Versus Multicelled Organisms"\n\nhttp://www.the-scientist.com/community/posts/list/200/122.page#3489\n\nFrom sensing to signalling to tumbling to re-swimming. This goes on in a bacterial cell. Who and how assesses the information and draws and issues instructions? \n\n\nC. 21st Century Science Is Still Blind To Gene's Lifehood\n\nThis blindness is one of the hallmarks of the scientifically decadent corrupt still ongoing 20th century technology culture.\n\n\nD. Cells are just the functional housings of the organisms genes-genome\n\nNature evolved genes to constrain energy as long as possible and to replicate for augmenting the amount of constrained energy.\n\nGenes evolved the capability and technique first to adapt and later to manipulate their environments by means of their expressions. Their expressions handle everything for the genes, from sensing to remembering to signaling through foraging through all components of surviving. Each and all of their expressions are targeted for augmented constrained energy survival.\n\nIs this so difficult to notice and accept scientifically?\n\nIt seems that mundane scientific decadence blinds 21st century science to the lifehood of genes.\n\n\nDov Henis\n(Comments From The 22nd Century)\nUpdated Life's Manifest May 2009 \nhttp://www.the-scientist.com/community/posts/list/140/122.page#2321\nImplications Of E=Total[m(1 + D)] \nhttp://www.the-scientist.com/community/posts/list/180/122.page#3108
Avatar of: denil corn

denil corn

Posts: 1

October 9, 2009

Alan R. Templeton, Ph.D., professor of biology in Arts and Sciences at Washington University, has analyzed DNA from global human populations that reveal the patterns of human evolution over the past one million years. He shows that while there is plenty of genetic variation in humans, most of the variation is individual variation. While between-population variation exists, it is either too small, which is a quantitative variation, or it is not the right qualitative type of variation -- it does not mark historical sublineages of humanity. This means Race doesn't matter. In fact, it doesn't even exist in humans, that, in the scientific sense, the world is colorblind. "Race is a real cultural, political and economic concept in society, but it is not a biological concept, and that unfortunately is what many people wrongfully consider to be the essence of race in humans.
Avatar of: MURTHY PUVVADA

MURTHY PUVVADA

Posts: 3

October 9, 2009

The usability of this information rests on one important yardstick: definition of 'normal, healthy' individuals.
Avatar of: anonymous poster

anonymous poster

Posts: 85

October 10, 2009

\n\nI fully appreciate what Dov Henis is trying to say, and in fact I agree that living systems, even (perhaps especially) at the cellular and subcellular level, possess the remarkable "life property" of adaptation to environmental ("environmental" broadly writ) signals which results in reprogramming of gene expression (sometimes with irreversible consequences). This has been described experimentally in cell culture systems where such processes would not have been expected based on current paradigms by several reports from different labs over the past several years. And of course it happens in every organism in the process of differentiation (even bacteria undergo differentiation, e.g., in response to quorum sensing). \n\nHowever, while the genome ("the genes") do not dictate a static situation for the cell or the organism, they do provide the overarching information from which the cell draws upon. Thus, the emphasis on the genome and on the "genes" at this point in our scientific inquiry is well justified and worthwhile. And we should not forget that some of our genome does not necessarily code for proteins but rather "codes" for expression-related functions and also for ____ (yet to be discovered, fill in the blank!). And some of the proteins are themselves agents of gene expression reprogramming, such as transcription factors, histones, or proteins involved in signal transduction mechanisms. Once we understand the genetic material, and once we understand the molecular and physical-chemical interactions that turn them on or off, or even cause them to undergo somatic recombination (a phenomenon well understood for higher vertebrate immmunology, but not yet not well understood or even yet recognized for other systems), then we can begin to ask good, meaningful questions based on the issues raised by Dov Henis. \n\nBTW, mathematical modeling (including chaos theory, which has already proved useful for biological systems) and "systems analysis" methodologies will be increasingly useful for this purpose.
Avatar of: Dov Henis

Dov Henis

Posts: 97

October 10, 2009

Not Just Genes Lifehood\n\nRe the 2009-10-10 07:37:19 comment\nby anonymous poster\non Dov Henis' comments\n\nThe scope of the issue is not just the lifehood of genes.\n\nI suggest and urge looking up the two succinct refs. They are the basis of a unified field theory covering the universe big bang inflation-gravity-expansion-E/m transformations-impansion back to E/m superposition.\n\n\nDov Henis \n(Comments From The 22nd Century) \nUpdated Life's Manifest May 2009 \nhttp://www.the-scientist.com/community/posts/list/140/122.page#2321 \nImplications Of E=Total[m(1 + D)] \nhttp://www.the-scientist.com/community/posts/list/180/122.page#3108

October 11, 2009

\n\nStimulating article and comments! Thanks!\n\nIt brought me memories of the first lessons I learned with my first book on Biology by Paul Weiss. That was quite sometime ago. In that interval of time, my concept of life has been expanded and resituated thanks to the creative work of so many more authors.\n\nLife, in its multiple forms and systems, appeared to have originated in a simple but rich context, (Paul Weiss called it ?soup? with atoms and molecules), that expanded in diversity and complexity and yet the emphasis appear to be in commonness. Why and how? I have no answers.\n\nRecent stories of science, ribosomes and telomeres, are reminiscent of a forth-back-forth process generated by and from commonness and yet the incorporation of unique elements appeared to have conferred unprecedented advantages for life and function. Perhaps, commonness has to do with an intrinsic strive for survival. Uniqueness might drive life, in its inherent dynamism, to a higher dimension ??.\n\nWhat might be going wrong in a process, presumably intended, to create productively efficient beautiful living systems? What kind of internal and/or external interventions might be triggering inefficiency or dysfunction?. \n\nNo answer, just questions but the feeling is that life in its commonness and uniqueness has only one destiny: life itself. We are alive and on our way home to life.\n\nEnya says it very nicely in the song: On my way home\n\n\nOn my way home\nI remember\nonly good days\nOn my way home \nI remember all \nthe best days\nAnd on my way home\nI can remember \nevery new day.\n

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BD Biosciences
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