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Posts Tagged ‘genomes’

The genetic sequence has been published only in its raw state, not yet assembled into a more usable form. When the process is completed, though, it should be possible to isolate the genes responsible for the creation of the pharmaceutically active compounds by the plant, including THC, CBD, and some 60 other cannabinoids. Understanding these genes and their expression will make possible a fine degree of control over the production of these compounds, with significant implications for both the medical and recreational users of the drug. Particular drug-producing genes could be isolated and concentrated in particular strains of the plant, or even inserted in other species.

The genome of C. sativa is roughly 400 million base pairs long; the human genome has 3 billion.

[Nature News]

Using a new genome engineering method, researchers from Harvard University and MIT were able to systematically replace one three-letter DNA “word,” or codon, with another one, throughout the entire genome. Their method reimagines genomes as editable templates, allowing entire sections to be rewritten without interrupting the overall organizational structure.

Ever since genome sequences were unraveled, scientists have been experimenting with ways to edit them, to give cells new capabilities and to cure diseases. But progress has been slow, in part because the editing job must be incredibly precise — one misplaced allele on a chromosome can be lethal. Introducing individual changes is therefore laborious and difficult.

Genetic scissors like zinc-finger nucleases can do the job, glomming on to certain sequences of a genome and cutting it out. Engineered viruses can then bring new DNA to the targeted area. Just last month, researchers successfully snipped out the genes that cause hemophilia, in a study involving living mice.

Rather than using scissors, this new method is akin to the find-and-replace function on your word processor, seeking out individual codons and replacing all of them with something new. The researchers used E. coli bacteria and edited a codon that only appears 314 times in the genome, spelled TAG.

Most codons spell out the sequence of an amino acid, as a Harvard Medical School news release explains. But some codons direct a cell to stop adding amino acids to a protein chain. TAG is one such stop codon, and it happens to be the rarest word in the E. coli genome. The team used a method called multiplex automated genome engineering, or MAGE, to replace the TAG codon with another stop codon, TAA.

MAGE locates specific DNA sequences and replaces them with a new sequence as the cell copies its DNA. The team made 32 E. coli strains, each of which had 10 TAG codons replaced. Then they used a new technique called conjugative assembly genome engineering (CAGE), which allowed them to control the process that bacteria use to swap genetic material.

An evolutionary tournament of sorts reduced the number of strains to 16, each with double the amount of TAG edits that it started with; ultimately, a final four strains had one-fourth of all their TAGs replaced, MIT News explains.

The researchers believe they’re on track to replace all 314 of them — without harming the cells in any way.

The next step would be to take out the genetic sequences that allow the cell to read the TAG stop instructions. This machinery could then be used for an entirely new purpose, like encoding a new protein or function.

The research is described in today's issue of the journal Science.

[MIT News]

Scientists say the research is a major step forward for gene therapy, which has long promised to cure disease by editing genetic sequences.

The therapy is based on enzymes called zinc-finger nucleases, which serve as a sort of genetic scissors. The enzymes are engineered to match a specific gene location on a chromosome, where they snip through DNA’s double helix.

In this case, researchers led by Katherine A. High, a hematologist and gene therapy expert at The Children’s Hospital of Philadelphia, used ZFN proteins that were engineered to snip through the location of a genetic mutation that causes hemophilia. Hemophiliacs lack a blood-clotting factor made by the liver that helps stanch bleeding, so their blood cannot clot, meaning minor injuries can be life-threatening.

High and colleagues had to take another step in their research, because hemophilic mice have a different genetic mutation than humans. They engineered mice to express the faulty human sequence, located on the F9 gene, and they designed ZFNs to cut through it. Then they engineered a virus that targets the liver (where the blood clotting factor is made) to carry the normal, unmutated version of F9.

As a result, the mutated section was removed, and the unmutated gene was inserted instead. Then the DNA molecule is stimulated to repair itself, sewing the new gene in place.

This is an improvement over other genetic editing techniques that use viruses to cut and paste the new genes. Although they have been shown to work, viral therapy has some inherent problems, including unpredictable chromosomal insertion, which can induce unwanted mutations. But the ZFN is designed to home in on a precise location of mutated DNA.

After this treatment, the animals’ blood clotted in 44 seconds, compared with more than a minute for hemophiliac mice, according to Nature.

The study shows that zinc finger proteins and replacement genes can be used to induce changes in living animals, which is promising for a wide range of therapies. For instance, other researchers are using ZFNs to disrupt a gene that makes a receptor used by the AIDS virus, as the New York Times reports. People without that gene, CCR5, are naturally immune to HIV.

The mouse study is reported in this week's issue of the journal Nature.

[via Science Daily]

Entomologists are submitting suggestions for 5,000 insects and other arthropods whose genomes should be sequenced, in a hunt for vulnerable regions that can be targeted with pesticides. The five-year 5000 Insect and Other Arthropod Genome Initiative, otherwise known as the i5K Initiative, will target insects that are known to be important to worldwide agriculture, food safety and medicine, among other impacts.

The study will examine insects that serve as disease transmitters and close relatives that do not, so researchers can compare genes that make some insects disease vectors and others benign. Certain species of mosquito, for instance, carry diseases like malaria or yellow fever, while other species do not, and understanding the genomic difference could help fight the disease-carrying types.

Pinpointing the genes that cause susceptibility to pesticides could actually help beneficial insects, like bees, while eradicating harmful ones from farm fields. Geneticists could mine data for specific detoxification genes found in certain insects, said Kevin J. Hackett, a national program leader at the USDA Agricultural Research Service, in an interview in the magazine American Entomologist.

“If we know about those genes from one insect to another, we can use that information to actually kill the insects," he said. “Or if you take beneficial insects like honey bees, which do not have as many detoxifying genes and are more susceptible to chemicals, that kind of information could be used to help protect bees.”

The project is feasible now because the costs of genetic sequencing have fallen sharply in recent years. As researchers begin sequencing genomes, they will be available on several public domain databases, entomologists said.

Do you know a lot about bugs, or the troubles they cause? Click here to nominate a species for sequencing.

[via BBC]

[via Gizmodo]

Happy V-D!

Gonorrhea is one of very few diseases exclusive to our species, and is one of the oldest recorded diseases in human history. An ancient disease that resembles gonorrhea’s symptoms is even described in the Bible, according to Hank Seifert, senior author of a paper on the gene transfer.

The bacterium apparently picks up a genetic sequence from the host it is infecting, a novel ability that could help the bacteria adapt to its host, according to Seifert, a microbiology and immunology professor at Northwestern University Feinberg School of Medicine. This ability may enable it to develop different strains of itself, he said. The paper is published today in the online journal mBio.

The human genome has plenty of ghost DNA fragments, relics of viruses that entered after some past infection. Lateral gene transfer is pretty common between bacteria and multicellular organisms, according to several studies. But this is the first time that scientists have seen a bacteria pick up the genes, rather than depositing them.

“Whether this particular event has provided an advantage for the gonorrhea bacterium, we don’t know yet,” Seifert said in a NU press release.

Scientists discovered the gene transfer while they were examining the genomic sequences of several gonorrhea strains. Three of them had a piece of DNA wherein the sequence was identical to a sequence found in humans, according to NU. Further examination suggests this evolved relatively recently.

About 700,000 Americans and 50 million people worldwide are infected with gonorrhea every year. It’s curable with an antibiotic, but it developed resistance to several drugs over the past 40 years. Studying the bacteria’s human DNA fragment could conceivably help scientists find better treatments.

“The next step is to figure out what this piece of DNA is doing,” Seifert said.

Of all the invertebrate genomes sequenced so far, the water flea shares the most with us, and scientists hope these shared genes can help them understand how humans respond to environmental threats.

The water flea, a shrimp relative, makes for an interesting subject because it can transform in response to stresses — it can develop spines, helmets or neck-teeth (really) in response to predator threats, according to scientists who participated in the sequencing project. They believe the vast number of genes is related to these abilities — itss gene expression patterns change depending on its environment. It has been compared to a modern mineshaft canary because of its responses to pollutants and environmental changes.

Now that scientists know what its genome looks like, and that it shares lots of genes with humans, they can start to study the environment’s effects on human health, too. James E. Klaunig, chair of the Environmental Health department at Indiana University, said the water flea will help scientists understand how environmental factors can affect cellular and molecular processes in animals.

It has only about 200 million bases, making the genome tightly packed. More than one-third of the flea’s genes have never been seen in any other creature and are brand-new to science. Many of those are duplicates, and they are the ones that are most responsive to ecological challenges, according to the journal Science, which publishes the genome sequence study today.

The copied genes surprised scientists by acting quite un-copy-like — they changed their functions really quickly. The scientists assumed the genes would have the same functions at first, and mutate into new roles with age, but that wasn’t the case; they seemed to switch functions immediately, possibly right when they were copied. This phenomenon produces a steady pool of genes that have different expressions, allowing the preservation of some new functions through natural selection, said Kelley Thomas, co-author and a genomics professor at the University of New Hampshire.

All of this may help scientists understand how organisms, including us, respond to changes in their environments, said Joseph Shaw, co-author and a biologist at Indiana University's School of Public and Environmental Affairs.

"With many shared genes between Daphnia and humans, we will now also apply Daphnia as a surrogate model to address issues directly related to human health," he said.