"Dark Matter' of the genome

Bishadi · Oct 13, 2011

http://www.sciencedaily.com/releases/2011/10/111012132655.htm

Their findings appear online October 12 in the journal Nature.

Early comparison studies of the human and mouse genomes led to the surprising discovery that the regulatory information that controls genes dwarfs the information in the genes themselves. But, these studies were indirect: they could infer the existence of these regulatory sequences, but could find only a small fraction of them. These mysterious sequences have been referred to as the dark matter of the genome, analogous to the unseen matter and energy that make up most of the universe
Click to expand...

eureka!

This new map helps pinpoint those mutations that are likely responsible for disease, as they have been preserved across millions of years of evolution, but are commonly disrupted in individuals that suffer from a given disease. Knowing the causal mutations and their likely functions can then help uncover the underlying disease mechanisms and reveal potential drug targets.

The scientists were able to suggest possible functions for more than half of the 360 million DNA letters contained in the conserved elements, revealing the hidden meaning behind the As, Cs, Ts, and Gs. These revealed:

Almost 4,000 previously undetected exons, or segments of DNA that code for protein

10,000 highly conserved elements that may be involved in how proteins are made

More than 1,000 new families of RNA secondary structures with diverse roles in gene regulation

2.7 million predicted targets of transcription factors, proteins that control gene expression

"We can use this treasure trove of new elements to revisit disease association studies, focusing on those that disrupt conserved elements and trying to discern their likely functions," said Kellis. "Using a single genome, the language of DNA seems cryptic. When studied through the lens of evolution, words light up and gain meaning
Click to expand...

waltky · Oct 4, 2012

Fast sequencing of baby DNA offers hope for ill infants...

Gene machines used to find cause of baby illnesses
Fri, Oct 05, 2012 - US scientists have sequenced the entire genetic code of four gravely ill newborns and identified genetic diseases in three of them in two days, quick enough to help doctors make treatment decisions.

Doctors behind the preliminary study released on Wednesday say it demonstrates a practical use for whole genome sequencing, in which researchers analyze all 3.2 billion chemical bases or letters that make up the human genetic code. It is now feasible to decode an entire genome and provide interim results back to the physician in two days, said Stephen Kingsmore, director of the Center for Pediatric Genomic Medicine at Childrens Mercy medical center in Kansas City, Missouri, whose study was published in the journal Science Translational Medicine. The study tested two software programs developed at Childrens Mercy that were used in conjunction with a high-speed gene sequencer from Illumina called HiSeq 2500, which can sequence an entire genome in about 25 hours. The company helped pay for the study and company researchers took part in it.

Next-generation gene sequencing machines have driven down the cost of whole genome sequencing, but making practical use of the data has been more challenging, largely because of the time it takes to analyze. As many as a third of babies admitted to a neonatal intensive care unit in the US have some form of genetic disease. Treatments are currently available for more than 500 diseases, but identifying them quickly has been a problem. Typically, genetic testing on newborns using conventional methods takes four to six weeks, long enough that the infant has either died or been sent home. Neil Miller, director of informatics at Childrens Mercy, said the software helps doctors identify which genes to test, and analyze the data quickly.

One of these programs, called SSAGA, allows doctors to order this test based on the childs symptoms, without having to know in advance which genes to test for. The software only maps genes associated with the childs symptoms. SSAGA does this for nearly 600 diseases, but the team is expanding this to include all 3,500 known disease genes, Miller told the briefing. The team developed a second software program called Runes that helps determine which of the suspected genes was most likely to be the cause of the childs illness.

Even though the study did not provide cures for the babies, she said, it could give parents more information about the cause of their childs illness. The test is projected to cost US$13,500, but the team believes that may be worth it given the high cost of care in a neonatal intensive care unit, which runs roughly US$8,000 per night. The next move is to broaden the test to include 100 or more babies to determine the benefits, costs and potential problems linked with the testing. Because the Illumina machine was not available in the US, the team had to discount the time it took to ship the blood samples to Britain, where the actual sequencing was done. However, Kingsmore said the hospital expects to receive its own HiSeq 2500 machine next month.

http://www.taipeitimes.com/News/world/archives/2012/10/05/2003544454
Click to expand...

See also:

'50-hour genome' test for babies with genetic diseases
4 October 2012 - Faster results mean sick babies can be given the correct medication

Doctors in the US say they have taken a big step forward in the speed of analysing the DNA of seriously ill babies with genetic diseases. The whole of a baby's genetic code - genome - was sequenced, analysed and the results given to doctors within 50 hours in intensive care units at Children's Mercy Hospital, Kansas City. The process would normally take at least a month, they said. Experts in the UK said it was an "impressive" technical achievement.

US doctors say up to a third of babies admitted to neonatal intensive care units are there because of genetic diseases caused by mutations in their DNA. However, there are more than 3,500 different genetic diseases meaning many are rare and difficult to diagnose. The first copy of the blueprint of human life - the Human Genome Project - took years to accomplish and an incredible amount of money. Since then both the time and the cost have fallen dramatically. Children's Mercy Hospital has been testing a new way of reading the genetic code which takes 50 hours from the moment a blood sample is taken. They were able to make a diagnosis in three out of the four babies they tested, according to a study published in Science Translational Medicine.

Costly business

Dr Stephen Kingsmore, director of the Center for Pediatric Genomic Medicine at the hospital, said: "We can now consider whole genome sequencing to be relevant for hospital medicine. "It is now feasible to decode an entire genome and provide interim results back to the physician in two days. "We think this is going to transform the world of neonataology." The results could help doctors provide the best treatment and counsel families. However, at a cost of about £8,400 ($13,500) it is still expensive.

Prof David Bonthron, from the University of Leeds, said: "It's pretty impressive technically, they're pushing the envelope of how fast you can turn this stuff around - two days is pretty fast." He said speed was also vital in analysing the genes of a foetus still in the womb if abnormalities have been identified. However, he added: "The speed issue is maybe a bit restricted in its applicability as other areas are not that time pressured. In outpatients a few days is not that important."

http://www.bbc.co.uk/news/health-19812067
Click to expand...

waltky · Apr 17, 2013

Pronounced Sea-la-canth...

'Living fossil' coelacanth genome sequenced
17 April 2013 - The genetic secrets of a "living fossil" have been revealed by scientists.

Researchers sequenced the genome of the coelacanth: a deep-sea fish that closely resembles its ancestors, which lived at least 300 million years ago. The study found that some of the animal's genes evolved very slowly, giving it its primitive appearance. The work also shed light on how the fish was related to the first land-based animals. The coelacanth has four large, fleshy fins, which some scientists believe could have been the predecessors of limbs. It had been suggested that this fish was closely related to early tetrapods - the first creatures to drag themselves out of the ocean, giving rise to life on land. But the study, published in the journal Nature, suggested that another fish called the lungfish, which also has four limbs, had more genes in common with land-based animals.

Slow to change

The coelacanth can reach up to 2m-long and is found lurking in caves deep beneath the waves. It was thought to have been extinct for millions of years, until it turned up in a trawlerman's net off the coast of Africa in 1938. Its ancient appearance has earned it the title "living fossil" - but it is so elusive, that it has been hard to study. To find out more, an international team of researchers sequenced the coelacanth's genome, which contained nearly three billion DNA bases.

The coelacanth is thought to have changed very little over millions of years

Professor Kerstin Lindblad-Toh, from the University of Uppsala in Sweden and the Broad Institute of MIT and Harvard in the US, said: "What we can see is that while the genome as whole changes, the protein-coding genes - that make the living fish - are much more stable and much more unchanging. "And if you think about it, this might be correlated to the fact that the coelacanth lives in a rather extreme and stable environment. "It lives several hundred metres down in the ocean, and it may also be in an environment where it doesn't have a lot of competitors. So maybe it adapted to that environment a long time ago and it doesn't have a huge need for change."

The researchers also used the study to try and solve the long-standing question of whether the first tetrapods were more closely related to the coelacanth or the lungfish. They compared DNA profiles of both of these fish with modern land-based animals, including mammals, birds and lizards. "We selected 251 genes that were very similar in all these genomes so we could build this picture of how closely related these species were," Prof Lindblad-Toh explained. "From that picture it was clear the lungfish is closer to tetrapods than the coelacanth."

Commenting on the research, John Hutchinson, professor of evolutionary biomechanics from the Royal Veterinary College, said it was an interesting study. "The lungfish-coelacanth question has gone back and forth over the years; the lungfish answer is not new, but this is a much better, bigger dataset so it does tip the balance a bit," he said. "They are missing some critical animals - it would be interesting to see what addition of salamander or more ray-finned fish would do to their analysis, but it might not change anything important."

This study is not the only one attempting to understand the coelacanth. Since the fish was rediscovered in the 1930s, only a few hundred have ever been found, many of these dead caught up in trawls. Scientists from the French organisation Andromede Oceanology are working with the Natural History Museum in Paris to attach acoustic tracking devices to the fish in order to study their behaviour and capture 3D moving images of their fins as they swim.

http://www.bbc.co.uk/news/science-environment-22184556
Click to expand...

Log in or Sign up

"Dark Matter' of the genome

Bishadi Banned

waltky Well-Known Member

waltky Well-Known Member

Share This Page

Log in or Sign up

"Dark Matter' of the genome

Bishadi Banned

waltky Well-Known Member

waltky Well-Known Member

Share This Page

Useful Searches