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Giant gene banks take on disease

Posted: October 15, 2014 at 9:46 am

Joe Raedle/Getty

Vast stores of DNA samples and data have been produced by the increasing pace of genetic sequencing.

Early last year, three researchers set out to create one genetic data set to rule them all. The trio wanted to assemble the worlds most comprehensive catalogue of human genetic variation, a single reference database that would be useful to researchers hunting rare disease-causing genetic variants.

Unlike past big data projects, which have involved large groups of scientists, this one deliberately kept itself small, deploying just five analysts. Nearly two years in, it has identified about 50million genetic variants points at which one persons DNA differs from anothers in whole-genome sequence data collected by 23other research collaborations. The group, called the Haplotype Reference Consortium, will unveil its database in San Diego, California, on 20October, at the annual meeting of the American Society of Human Genetics.

Geneticists have not always been so willing to share data. But that seems to be changing. Its been surprisingly easy to bring all these data sets together, says Jonathan Marchini, a statistical geneticist at the University of Oxford, UK, and one of the consortiums leaders. There is a lot of goodwill between the people in the field; they all understand the benefits of doing this and have worked hard to make their data available.

In the past five years, there has been an explosion in rates of sequencing human genomes thanks to the falling cost of the technology. At the same time, geneticists have realized that linking genes to diseases and traits will require much bigger sample sizes than any one research centre can assemble.

It was once assumed that common diseases and traits could be traced to a few common genetic variants that would be relatively easy to find. But that has turned out not to be the case. It is now clear that thousands of different variants each play a small part in determining a persons height or risk of schizophrenia, for example. And finding those thousands of variants means looking at a daunting number of people. At the same time, the increased pace of genetic sequencing has made it possible to collect enough genomes to uncover those variants.

Here are a bunch of data sets that individually cost millions of dollars to generate, and you have people willing to make that data available to a shared resource, which is amazing, says geneticist Daniel MacArthur of Massachusetts General Hospital in Boston.

MacArthur is part of the Exome Aggregation Consortium, another attempt to create a supersized library of human genetic variation. On 20October, MacArthur and his colleagues plan to unveil their own public database containing the protein-coding portions, or exomes, of 63,000 human genomes originally gathered by other researchers. We can say from looking at a very large cohort of peoplethis is what the distribution of rare variation looks like, says MacArthur. And that is very powerful.

MacArthur is developing tools to comb the data for mutations that disable genes. Only some of these loss-of-function mutations cause harm; predicting which are pathogenic will require knowing more about which ones regularly occur in healthy people.

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Giant gene banks take on disease

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Dr Brock Foru DNA part 1 – Video

Posted: at 9:45 am


Dr Brock Foru DNA part 1
Dr Brock discusses DNA test http://www.lovingourchildren.foru.com.

By: Elia Arriaga

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Dr Brock Foru DNA part 1 - Video

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Dr Brock DNA Part 3 – Video

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Dr Brock DNA Part 3
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By: Elia Arriaga

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Dr Brock DNA Part 3 - Video

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Dr Brock DNA Part 2 – Video

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Dr Brock DNA Part 2
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By: Elia Arriaga

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Dr Brock DNA Part 2 - Video

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Loka – D.N.A – Video

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Loka - D.N.A

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Abhishek Bachchan Flags Off DNA Womens Half Marathon – Video

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Abhishek Bachchan Flags Off DNA Womens Half Marathon
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Abhishek Bachchan Flags Off DNA Womens Half Marathon - Video

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Andy Falco ~ Adam Gieckel ~ DNA – Video

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Andy Falco ~ Adam Gieckel ~ DNA
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Andy Falco ~ Adam Gieckel ~ DNA - Video

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Abhishek Bachchan Flags Off The DNA Women’s Half Marathon – Video

Posted: at 9:45 am


Abhishek Bachchan Flags Off The DNA Women #39;s Half Marathon
Bollywood Actor Abhishek Bachchan Flags Off The DNA Women #39;s Half Marathon. Visit - https://www.unitezz.com . India #39;s Biggest Bollywood Entertainment Website for More Exclusives Like us on...

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Abhishek Bachchan Flags Off The DNA Women's Half Marathon - Video

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niall horan // d n a – Video

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niall horan // d n a
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Charged graphene gives DNA a stage to perform molecular gymnastics

Posted: at 9:45 am

When Illinois researchers set out to investigate a method to control how DNA moves through a tiny sequencing device, they did not know they were about to witness a display of molecular gymnastics.

Fast, accurate and affordable DNA sequencing is the first step toward personalized medicine. Threading a DNA molecule through a tiny hole, called a nanopore, in a sheet of graphene allows researchers to read the DNA sequence; however, they have limited control over how fast the DNA moves through the pore. In a new study published in the journal Nature Communications, University of Illinois physics professor Aleksei Aksimentiev and graduate student Manish Shankla applied an electric charge to the graphene sheet, hoping that the DNA would react to the charge in a way that would let them control its movement down to each individual link, or nucleotide, in the DNA chain.

"Ideally, you would want to step the DNA through the nanopore one nucleotide at a time," said Aksimentiev. "Take a measurement and then have another nucleotide in the sensing hole. That's the goal, and it hasn't been realized yet. We show that, to some degree, we can control the process by charging the graphene."

The researchers found that a positive charge in the graphene speeds up DNA movement through the nanopore, while a negative charge stops the DNA in its tracks. However, as they watched, the DNA seemed to dance across the graphene surface, pirouetting into shapes they had never seen, specific to the sequence of the DNA nucleotides.

"It reminds me of Swan Lake," Aksimentiev said. "It's very acrobatic. We were very surprised by the variety of DNA conformations that we can observe at the surface of graphene when we charge it. There is one sequence that starts out laying down on the surface, and when we change the charge, they all tilt on the side like they are doing a one-armed push-up. Then we also have nucleotides that would lay back, or go up like a ballerina en pointe."

Aksimentiev hypothesizes that the conformations are so different and so specific to the sequence because each nucleotide has a slightly different distribution of electrons, the negatively charged parts of the atoms. There is even a visible difference when a nucleotide is methylated, a tiny chemical change that can turn a gene on or off.

By switching the charge in the graphene, the researchers can control not only the DNA's motion through the pore, but also the shape the DNA contorts into.

"Because it's reversible, we can force it to adopt one conformation and then force it to go back. That's why we call it gymnastics," Aksimentiev said.

The researchers extensively used the Blue Waters supercomputer at the National Center for Supercomputing Applications, housed at the University of Illinois. They mapped each individual atom in the complex DNA molecule and ran numerous simulations of many different DNA sequences. Supercomputing power was essential to carrying out the work, Aksimentiev said.

"This is a really computationally intensive project," he said. "Having access to Blue Waters was essential because with the sheer number of simulations, we would not have been able to finish them. It would have taken too long."

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