Daily Archives: March 2, 2013

Feb. 28, 2013 Earth Day may be more than a month away, but another, more personal, ecosystem has been shown to also be worth protecting -- within our bodies are communities of microbes that affect the behavior of human cells hosting them. These communities, called the "microbiome," is so crucial to our health that some consider it to be a complex "second genome." Understanding the interaction of these microbes among one another and their human hosts has the potential to yield insights into numerous diseases and complex human disorders from obesity to susceptibility to infection.

In a new report appearing in the March 2013 issue of The FASEB Journal, scientists take an important step toward designing a uniform protocol for microbiome research that ensures proper controls and considerations for variations among people. By doing this, future researchers should be able to better assess how what we ingest, whether drugs or food, affects our bodies.

"While historically pre and probiotics have dominated the microbiome landscape, emerging data from numerous labs as to the impact of dietary interventions and antibiotic exposure will play formative roles in tailoring therapy," said Kjersti M. Aagaard, M.D., Ph.D., from the Department of Obstetrics and Gynecology at Baylor College of Medicine in Houston, Texas. "We may find that the answers to our most common and prevalent health and disease states lies not in manipulating the human genome, but rather, in utilizing subtle shifts in diet and components of the diet, efficacy trials in prophylactic or preventative antibiotic therapies, and care attention to the over prescription of steroids and antibiotics."

Aagaard and colleagues completed comprehensive body site sampling in healthy 18-40 year old adults, creating an unparalleled reference set of microbiome specimens. Researchers then screened 554 individuals to enroll 300 (149 males, 151 females, mean age 26, mean BMI 24, 20.0 percent racial minority and 10.7 percent Hispanic). Scientists obtained specimens from several body sites to evaluate the longitudinal changes in an individual's microbiome by sampling 279 participants twice (mean 212 days after first sampling, range 30-359), and 100 individuals three times (mean 72 days after second sampling, range 30-224). This sampling strategy yielded 11,174 primary specimens, from which 12,479 DNA samples were submitted to four centers for metagenomic sequencing. This clinical design and well-defined reference cohort has laid a baseline foundation for microbiome research.

"Whether it is yogurt, penicillin, or diet soda, each alters the microbial communities that live within us," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "This pioneering study promises to provide their names and numbers, so that we can understand how diet, disease or drugs affect our internal ecosystem."

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The above story is reprinted from materials provided by Federation of American Societies for Experimental Biology, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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After the human genome project: The human microbiome project

Photo: Ava Helen and Linus Pauling Papers/ Oregon State University Libraries Photo 51: This historic X-ray diffraction image of DNA, taken in 1952 by Rosalind Franklin and Raymond Gosling, was obtained by stretching a fragile thread of crystalline DNA across a paper clip stuck in a cork, passing an X-ray beam through it for 100 hours, and capturing the results on photographic paper. Click on image to enlarge.

Next month marks the 60th anniversary of the discovery of the double helix structure of DNA by James Watson and Francis Crick. To ordinary folks, the image (known as Photo 51) that confirmed the Watson-Crick model doesnt look like anything. But without this imageand without the brilliant work of X-ray crystallographer Rosalind Franklinthe Cambridge lads had a theory and a model but no actual proof that DNA was indeed the molecule of life. It took Franklins technical know-how and perseverance for that secret to be revealed.

Biology is now one of many sciences thats almost completely dependent on technology: The technologies that allow us to view human biology at the molecular level have driven the genomic revolution. Automation, robotics, high-speed processors, and sophisticated computer programs have taken what was once the painstaking handwork of DNA identification, isolation, preparation, and sequencing and turned them into digital processes. The first sequencing of the human genome took 13 years and US $3 billion. Now machines the size of a multipurpose office printer will soon be able to do the same for sums of about $1000, and all in a days time.

But what will this mean on a human level? Eliza Stricklands article in this issue, The Gene Machine and Me, is about her very personal experience with Ion Torrents semiconductor-based genome-sequencing machines. These machines, which turn chemical signals into digital form, are the latest demonstration of the powerful electronic technologies driving all things genomic. In an echo of events 60 years ago, when several labs [PDF] competed to discover the true nature of DNA, several companies are now racing to create genomic technology for widespread use.

Why is this significant? After all, for $100 you can already send away a bit of spit to a direct-to-consumer DNA testing company like 23andMe. Their results will tell you if youre related to Genghis Khan, carry disease traits you could pass on to your children, or have an elevated risk of developing diabetes. These companies use a technology that examines the million points on the genome that vary among individuals.

But being able to predict, prevent, or treat disease based on the sequencing of your entire genomewhich is made up of 3 billion componentsis a far more complicated business. Its also more rewarding. The collection and analysis of large sets of individual genomes should eventually help researchers establish the root causes of complex diseases and allow them to create individualized treatment and even cures.

Patient-driven, personalized, precision medicine has significant hurdles to overcome, and not just technical ones. One of the most important is how to sequence millions, if not billions, of people to broaden our understanding of which genes correspond to which disease vulnerabilities, as well as other inherited characteristics. And while were doing that, well need to develop more big-data software programs to sift through all the information from these genomesa single human genome alone is about 4 gigabytes.

Other big challenges include training doctors to use genomic information in their practices, getting pharmaceutical companies to give up their blockbuster drug revenue model, and goading insurance companies into abandoning their rigid reliance on actuarial tables. And all this must happen as we simultaneously take on the inevitable genetic discrimination problems and myriad other ethical issues that will spring up.

As the former editor of a biotechnology journal, I have seen lots of breakthroughs, revolutions, and quantum leaps heralded as being on the brink of transforming our lives forever. But these transformations never occur overnight and take years, often decades, to reveal themselves.

Thats the case with human genomics and its impact on medicine. Genetics has been poised to change medicine since Gregor Mendel tended his peas. In 10 years or so, after weve all had our genomes sequenced and are toting them around on our tricorders, the benefits for medicine of genome sequencing and its attendant technologies should become truly apparentas will all the tics and bumps that make each of us uniquely human.

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Genome to Go

March 2, 2013

Brett Smith for redOrbit.com Your Universe Online

According to a report in the journal Nature Genetics, an international team of geneticists has announced the successful sequencing of the sea lamprey genome.

The sea lamprey makes for an interesting genetic case from an evolutionary standpoint, being a jawless vertebrate that diverged from jawed vertebrates millions of years ago.

The sea lamprey is a primitive jawless vertebrate that diverged from other jawed vertebrates early in the vertebrate ancestry, said co-author David McCauley, from Oklahoma University, in a statement. Because of its early divergence from other living vertebrates, the sea lamprey genome can provide insights for understanding how vertebrate genomes have evolved, and the origins of vertebrate character traits.

McCauley explained that vertebrates have multiple copies of many genes in their genome as the result of two whole-genome rounds of genetic duplication.

One outstanding question has been the timing of these duplications in vertebrate history, he said. Results from this project suggest that two rounds of duplication predated the divergence of the ancestral lamprey from modern jawed vertebrates. This result is important for understanding how vertebrate genomes have evolved, and in particular, for understanding if the organization of the genome is common to all vertebrates.

The OU geneticist added that the lampreys unique neural physiology makes for an interesting genomic and evolutionary study.

Most vertebrates contain an insulating layer of cells that surround nerve cells, he said. Cells that wrap around a nerve fiber, or axon, are enriched in a protein known as myelin. The insulating properties of myelin allow signals to be conducted rapidly along the nerve fiber, and the loss of myelin results in numerous neurodegenerative diseases in humans.

McCauley said the neurons within lampreys are unwrapped, suggesting that the insulation is specific to jawed vertebrates.

Excerpt from:
Geneticists Complete Sea Lamprey Genome Sequencing

Public release date: 28-Feb-2013 [ | E-mail | Share ]

Contact: Angela Startz astartz@ou.edu 405-325-6664 University of Oklahoma

Beginning in 2004, a group of scientists from around the globe, including two University of Oklahoma faculty members, set out to map the genome of the sea lamprey. The secrets of how this jawless vertebrate separated from the jawed vertebrates early in the evolutionary process will give insight to the ancestry of vertebrate characters and may help investigators more fully understand neurodegenerative diseases in humans.

David McCauley, associate professor in the Biology Department in the OU College of Arts and Sciences, and Sandra W. Clifton, with the OU Center for Advanced Genome Technology, collaborated with scientists from Japan, Germany, the United States, Canada and Great Britain.

McCauley isolated and prepared the liver tissue from the single adult female sea lamprey, from which genomic DNA was isolated for sequencing. Clifton was involved in management of the sea lamprey sequencing project at the Genome Institute at Washington University in St. Louis until her retirement in 2010. The project then was taken over by Patrick Minx. Clifton participated in the discussions regarding the paper preparation, and she is a senior author on the paper. Sequencing was performed at the Genome Institute and the project was directed by Weiming Li at Michigan State University with funding provided by the National Human Genome Research Institute at the National Institutes of Health.

"The sea lamprey is a primitive jawless vertebrate that diverged from other jawed vertebrates early in the vertebrate ancestry," writes McCauley. "Because of its early divergence from other living vertebrates, the sea lamprey genome can provide insights for understanding how vertebrate genomes have evolved, and the origins of vertebrate character traits. Several important findings arise from sequencing the sea lamprey genome: Vertebrates have undergone two 'whole-genome' rounds of duplication, resulting in multiple copies of many genes present in vertebrates. One outstanding question has been the timing of these duplications in vertebrate history. Results from this project suggest that two rounds of duplication predated the divergence of the ancestral lamprey from modern jawed vertebrates. This result is important for understanding how vertebrate genomes have evolved, and in particular, for understanding if the organization of the genome is common to all vertebrates.

"Most vertebrates contain an insulating layer of cells that surround nerve cells. Cells that wrap around a nerve fiber, or axon, are enriched in a protein known as myelin. The insulating properties of myelin allow signals to be conducted rapidly along the nerve fiber, and the loss of myelin results in numerous neurodegenerative diseases in humans."

McCauley adds that lampreys lack these "wrapped" neurons, suggesting the insulated neurons are specific to jawed vertebrates. "Somewhat surprisingly, the sea lamprey genome contains multiple proteins involved in the synthesis of myelin, including its basic protein. This important finding suggests the origin of myelin predated the divergence of lampreys from the lineage leading to jawed vertebrates, but the role of these proteins in lampreys is not known. Other important findings shed light on evolution of the vertebrate adaptive immune system, and the evolution of paired appendages, such as fins in fish and fore-limbs and hind-limbs in tetrapod vertebrates such as humans and animals."

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The findings recently were published in the March issue of Nature Genetics. To read the full article, visit http://www.nature.com/ng.

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Sea lamprey genome mapped with help from scientists at OU

Feb. 28, 2013 Beginning in 2004, a group of scientists from around the globe, including two University of Oklahoma faculty members, set out to map the genome of the sea lamprey. The secrets of how this jawless vertebrate separated from the jawed vertebrates early in the evolutionary process will give insight to the ancestry of vertebrate characters and may help investigators more fully understand neurodegenerative diseases in humans.

David McCauley, associate professor in the Biology Department in the OU College of Arts and Sciences, and Sandra W. Clifton, with the OU Center for Advanced Genome Technology, collaborated with scientists from Japan, Germany, the United States, Canada and Great Britain.

McCauley isolated and prepared the liver tissue from the single adult female sea lamprey, from which genomic DNA was isolated for sequencing. Clifton was involved in management of the sea lamprey sequencing project at the Genome Institute at Washington University in St. Louis until her retirement in 2010. The project then was taken over by Patrick Minx. Clifton participated in the discussions regarding the paper preparation, and she is a senior author on the paper. Sequencing was performed at the Genome Institute and the project was directed by Weiming Li at Michigan State University with funding provided by the National Human Genome Research Institute at the National Institutes of Health.

"The sea lamprey is a primitive jawless vertebrate that diverged from other jawed vertebrates early in the vertebrate ancestry," writes McCauley. "Because of its early divergence from other living vertebrates, the sea lamprey genome can provide insights for understanding how vertebrate genomes have evolved, and the origins of vertebrate character traits. Several important findings arise from sequencing the sea lamprey genome: Vertebrates have undergone two 'whole-genome' rounds of duplication, resulting in multiple copies of many genes present in vertebrates. One outstanding question has been the timing of these duplications in vertebrate history. Results from this project suggest that two rounds of duplication predated the divergence of the ancestral lamprey from modern jawed vertebrates. This result is important for understanding how vertebrate genomes have evolved, and in particular, for understanding if the organization of the genome is common to all vertebrates.

"Most vertebrates contain an insulating layer of cells that surround nerve cells. Cells that wrap around a nerve fiber, or axon, are enriched in a protein known as myelin. The insulating properties of myelin allow signals to be conducted rapidly along the nerve fiber, and the loss of myelin results in numerous neurodegenerative diseases in humans."

McCauley adds that lampreys lack these "wrapped" neurons, suggesting the insulated neurons are specific to jawed vertebrates. "Somewhat surprisingly, the sea lamprey genome contains multiple proteins involved in the synthesis of myelin, including its basic protein. This important finding suggests the origin of myelin predated the divergence of lampreys from the lineage leading to jawed vertebrates, but the role of these proteins in lampreys is not known. Other important findings shed light on evolution of the vertebrate adaptive immune system, and the evolution of paired appendages, such as fins in fish and fore-limbs and hind-limbs in tetrapod vertebrates such as humans and animals."

The findings recently were published in the March issue of Nature Genetics.

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Sea lamprey genome mapped

The human genome can generate molecular hoops similar in makeup to DNA that could potently interfere with genetic activity, researchers say.

These findings reveal there are secrets within the genomes of humans and other animals that scientists are still uncovering, and the old belief that life has useless junk DNA is more false than ever, scientists added.

Discovering more about circular versions of RNA (a molecule similar to DNA that can carry genetic information) could also lead to new ways of fighting diseases such as diabetes, brain tumors and Parkinson's disease, investigators added.

The human genome the blueprint for human life is made of DNA. From the genome, intermediate molecules known as RNA are created that help manufacture key biomolecules such as proteins, which then carry out cellular processes.

After international teams of researchers completely sequenced the human genome, they found about 95 percent of it unexpectedly did not code for proteins. Since this noncoding DNA initially seemed to have no known biological function, some scientists referred to it as junk DNA. [Unraveling the Human Genome: 6 Molecular Milestones]

However, over time, researchers have discovered this noncoding DNA can serve a wide variety of vital purposes. For instance, noncoding DNA can give rise to snippets of RNA known as micro-RNA that can suppress the so-called messenger RNA that normally helps manufacture proteins. This micro-RNA serves a key role in controlling genetic activity, and scientists are developing therapies based on micro-RNA to dampen harmful, malfunctioning genes.

Now researchers find the genomes of humans and other animals can generate circular RNA, highly stable rings that can sponge up micro-RNA, apparently keeping them from interfering with genetic activity if necessary.

"There seems to be a whole new layer of gene regulation," researcher Jrgen Kjems, a molecular biologist at Aarhus University in Denmark, told LiveScience.

For instance, Kjems and his colleagues found high levels of a circular RNA they dubbed ciRS-7 in the human and mouse brain. This molecule potently suppresses a micro-RNA named miR-7, which is found in everything from worms to humans. They also found a circular RNA known as Sry that is specific to testicles and targets a micro-RNA known as miR-138, suggesting that circular RNA might play a role in sex development.

In addition, when Nikolaus Rajewsky at the Max Delbrck Center for Molecular Medicine in Berlin and his colleagues analyzed human, mouse and nematode worm RNA, they detected thousands of circular RNAs. These were often linked with specific tissues or developmental stages.

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Weird Molecular Hoops Made From Human Genome