Archive for the ‘gene’ Category


Sixty trays can contain the entire human genome as 23,040 different fragments of cloned DNA. Credit James King-Holmes/Science Source

By ANDREW POLLACK

Scientists are now contemplating the fabrication of a human genome, meaning they would use chemicals to manufacture all the DNA contained in human chromosomes.

The prospect is spurring both intrigue and concern in the life sciences community because it might be possible, such as through cloning, to use a synthetic genome to create human beings without biological parents.

While the project is still in the idea phase, and also involves efforts to improve DNA synthesis in general.

Organizers said the project could have a big scientific payoff and would be a follow-up to the original Human Genome Project, which was aimed at reading the sequence of the three billion chemical letters in the DNA blueprint of human life. The new project, by contrast, would involve not reading, but rather writing the human genome — synthesizing all three billion units from chemicals.

But such an attempt would raise numerous ethical issues. Could scientists create humans with certain kinds of traits, perhaps people born and bred to be soldiers? Or might it be possible to make copies of specific people?

“Would it be O.K., for example, to sequence and then synthesize Einstein’s genome?” Drew Endy, a bioengineer at Stanford, and Laurie Zoloth, a bioethicist at Northwestern University, wrote in an essay criticizing the proposed project. “If so how many Einstein genomes should be made and installed in cells, and who would get to make them?”

The project was initially called HGP2: The Human Genome Synthesis Project, with HGP referring to the Human Genome Project. An invitation to the meeting at Harvard said that the primary goal “would be to synthesize a complete human genome in a cell line within a period of 10 years.”

But by the time the meeting was held, the name had been changed to “HGP-Write: Testing Large Synthetic Genomes in Cells.”

The project does not yet have funding, Dr. Church said, though various companies and foundations would be invited to contribute, and some have indicated interest. The federal government will also be asked. A spokeswoman for the National Institutes of Health declined to comment, saying the project was in too early a stage.

Besides Dr. Church, the organizers include Jef Boeke, director of the institute for systems genetics at NYU Langone Medical Center, and Andrew Hessel, a self-described futurist who works at the Bay Area software company Autodesk and who first proposed such a project in 2012.

Scientists and companies can now change the DNA in cells, for example, by adding foreign genes or changing the letters in the existing genes. This technique is routinely used to make drugs, such as insulin for diabetes, inside genetically modified cells, as well as to make genetically modified crops. And scientists are now debating the ethics of new technology that might allow genetic changes to be made in embryos.

But synthesizing a gene, or an entire genome, would provide the opportunity to make even more extensive changes in DNA.

For instance, companies are now using organisms like yeast to make complex chemicals, like flavorings and fragrances. That requires adding not just one gene to the yeast, like to make insulin, but numerous genes in order to create an entire chemical production process within the cell. With that much tinkering needed, it can be easier to synthesize the DNA from scratch.

Right now, synthesizing DNA is difficult and error-prone. Existing techniques can reliably make strands that are only about 200 base pairs long, with the base pairs being the chemical units in DNA. A single gene can be hundreds or thousands of base pairs long. To synthesize one of those, multiple 200-unit segments have to be spliced together.

But the cost and capabilities are rapidly improving. Dr. Endy of Stanford, who is a co-founder of a DNA synthesis company called Gen9, said the cost of synthesizing genes has plummeted from $4 per base pair in 2003 to 3 cents now. But even at that rate, the cost for three billion letters would be $90 million. He said if costs continued to decline at the same pace, that figure could reach $100,000 in 20 years.

J. Craig Venter, the genetic scientist, synthesized a bacterial genome consisting of about a million base pairs. The synthetic genome was inserted into a cell and took control of that cell. While his first synthetic genome was mainly a copy of an existing genome, Dr. Venter and colleagues this year synthesized a more original bacterial genome, about 500,000 base pairs long.

Dr. Boeke is leading an international consortium that is synthesizing the genome of yeast, which consists of about 12 million base pairs. The scientists are making changes, such as deleting stretches of DNA that do not have any function, in an attempt to make a more streamlined and stable genome.

But the human genome is more than 200 times as large as that of yeast and it is not clear if such a synthesis would be feasible.

Jeremy Minshull, chief executive of DNA2.0, a DNA synthesis company, questioned if the effort would be worth it.

“Our ability to understand what to build is so far behind what we can build,” said Dr. Minshull, who was invited to the meeting at Harvard but did not attend. “I just don’t think that being able to make more and more and more and cheaper and cheaper and cheaper is going to get us the understanding we need.”

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In an ethically charged first, Chinese researchers have used gene editing to modify human embryos obtained from an in-vitro fertilization clinic.

The 16-person scientific team, based at the Sun Yat-Sen University in Guangzhou, China, set out to see whether it could correct the gene defect that causes beta-thalassemia, a blood disease, by editing the DNA of fertilized eggs.

The team’s report showed the method is not yet very accurate, confirming scientific doubts around whether gene editing could be practical in human embryos, and whether genetically engineered people are going to be born anytime soon.

The authors’ report appeared on April 18 in a low-profile scientific journal called Protein & Cell. The authors, led by Junjiu Huang, say there is a “pressing need” to improve the accuracy of gene editing before it can be applied clinically, for instance to produce children with repaired genes.

The team did not try to establish a pregnancy and say for ethical reasons they did their tests only in embryos that were abnormal.

“These authors did a very good job pointing out the challenges,” says Dieter Egli, a researcher at the New York Stem Cell Foundation in Manhattan. “They say themselves this type of technology is not ready for any kind of application.”

The paper had previously circulated among researchers and had provoked concern by highlighting how close medical science may be to tinkering with the human gene pool.

n March, an industry group called for a complete moratorium on experiments of the kind being reported from China, citing risks and the chance they would open the door to eugenics, or changing nonmedical traits in embryos, such as stature or intelligence.

Other scientists recommended high-level meetings of experts, regulators, and ethicists to debate if there are acceptable uses for such engineering.

The Chinese team reported editing the genes of more than 80 embryos using a technology called CRISPR-Cas9. While in some cases they were successful, in others the CRISPR technology didn’t work or introduced unexpected mutations. Some of the embryos ended up being mosaics, with a repaired gene in some cells, but not in others.

Parents who are carriers of beta-thalassemia could choose to test their IVF embryos, selecting those that have not inherited the disease-causing mutation. However, gene editing opens the possibility of germline modification, or permanently repairing the gene in an embryo, egg, or sperm in a way that is passed onto the offspring and to future generations.

That idea is the subject of intense debate, since some think the human gene pool is sacrosanct and should never be the subject of technological alteration, even for medical reasons. Others allow that germline engineering might one day be useful, but needs much more testing. “You can’t discount it,” says Egli. “It’s very interesting.”

The Chinese team performed the gene editing in eggs that had been fertilized in an IVF clinic but were abnormal because they had been fertilized by two sperm, not one. “Ethical reasons precluded studies of gene editing in normal embryos,” they said.

Abnormal embryos are widely available for research, both in China and the U.S. At least one U.S. genetics center is also using CRISPR in abnormal embryos rejected by IVF clinics. That group described aspects of its work on the condition that it would not be identified, since the procedure remains controversial.

Making repairs using CRISPR harnesses a cell’s own DNA repair machinery to correct genes. The technology guides a cutting protein to a particular site on the DNA molecule, chopping it open. If a DNA “repair template” is provided—in this case a correct version of the beta-globin gene—the DNA will mend itself using the healthy sequence.

The Chinese group says that among the problems they encountered, the embryo sometimes ignored the template, and instead repaired itself using similar genes from its own genome, “leading to untoward mutations.”

Huang said he stopped the research after the poor results. “If you want to do it in normal embryos, you need to be close to 100 percent,” Huang told Nature News. “That’s why we stopped. We still think it’s too immature.”

http://www.technologyreview.com/news/536971/chinese-team-reports-gene-editing-human-embryo/

Thanks to Michael Moore for bringing this to the It’s Interesting community.

In our cells, proteins are the tiny machines that do most of the work. And the instructions for making proteins — and for piecing together their building blocks, called amino acids — are laid out by DNA, then relayed through RNA. But now, researchers show for the first time that amino acids can be assembled by another protein — without genetic instructions. These surprising findings were published in Science this week.

If a cell is an automobile-making factory, then ribosomes are the machines on the protein assembly line that links together amino acids in an order specified by DNA and messenger RNA (mRNA), an intermediate template. If something goes awry and a ribosome stalls, the quality control team shows up to disassemble the ribosome, discard that bit of genetic blueprint, and recycle the partially-made protein.

Turns out, that assembly line can keep going even if it loses its genetic instructions, according to a large U.S. team led by University of Utah, University of California, San Francisco, and Stanford researchers. They discovered an unexpected mechanism of protein synthesis where a protein, and not the normal genetic blueprint, specifies which amino acids are added.

“In this case, we have a protein playing a role normally filled by mRNA,” UCSF’s Adam Frost says in a news release. “I love this story because it blurs the lines of what we thought proteins could do.”

Frost and colleagues found a never-before-seen role for one member of the quality control team: a protein named Rqc2, which helps recruit transfer RNA (tRNA) to sites of ribosomal breakdowns (tRNA is responsible for bringing amino acids to the protein assembly line). Before the incomplete protein gets recycled, Rqc2 prompts the stalled ribosomes to add two amino acids — alanine and threonine — over and over. And that’s because the Rqc2–ribosome complex binds tRNAs that carry those two specific amino acids. In the auto analogy, the assembly line keeps going despite having lost its instructions, picking up whatever it can and attaching it in no particular order: horn-wheel-wheel-horn-wheel-wheel-wheel-wheel-horn, for example.

Pictured above, Rqc2 (yellow) binds tRNAs (blue and teal), which add amino acids (bright sot in the middle) to a partially-made protein (green). The complex binds the ribosome (white). A truncated protein with a seemingly random sequence of alanines and threonines probably doesn’t work properly, and that tail could be a code that signals for the malformed protein to be destroyed.

http://www.iflscience.com/health-and-medicine/protein-directs-protein-synthesis-without-dna-blueprint

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

by Lisa Winter

Over 200 million people are infected by malaria each year, and the majority of the 627,000 deaths per year are children younger than five. The disease is carried by mosquitos who act as vectors for the parasite. It’s only transmitted to humans by female mosquitoes, as they’re the only ones who bite. A team of researchers led by Andrea Crisanti of the Imperial College London managed to genetically modify mosquitos to produce 95% male offspring, eliminating mosquito populations along with the risk of malaria. The results of the study were published in Nature Communications.

In most species of mosquito, the females need a blood meal in order to acquire the nutrients to create viable eggs. When she does, she can lay about 200 eggs at a time in water, and up to 3,000 eggs over the course of her lifetime. About half of those offspring will be daughters, many of whom will live long enough to produce that amount of offspring also. For humans living near mosquitos carrying the parasite that causes malaria, those numbers of female mosquitos present a very real threat.

But what if the numbers could be skewed so that the sex ratio favors males, who are harmless to humans? This is exactly what Crisanti’s team set out to do with Anopheles gambiae, a species of mosquito endemic to sub-Saharan Africa, where 95% of malaria deaths occur. The researchers modified the males with the enzyme I-Ppol, which excises the X chromosome during spermatogenesis. This renders sperm that would produce daughters to be non-functional, while the sperm that will create male offspring are unaffected. As a result, about 95% of the resulting offspring are male.

Next, modified males were introduced to five caged wild-type populations. As the males mated with the females, they passed along the same mutation until it dominated the population. For four of the five populations, it took only six generations for the mosquitos to die out due to a lack of females.

“What is most promising about our results is that they are self-sustaining,” co-author Nikolai Windbichler said in a press release. “Once modified mosquitoes are introduced, males will start to produce mainly sons, and their sons will do the same, so essentially the mosquitoes carry out the work for us.”

This study was the first to successfully manipulate mosquito sex ratios, and it was done in a big way. The researchers hope that this information will be used to develop genetic mutations to be used in the wild, bringing large populations of mosquitos to their knees.

“The research is still in its early days, but I am really hopeful that this new approach could ultimately lead to a cheap and effective way to eliminate malaria from entire regions,” added lead author Roberto Galizi. “Our goal is to enable people to live freely without the threat of this deadly disease.”

Of course, while eradicating the mosquitos would be fantastic for eliminating the threat of malaria, what other affects would it have? Wouldn’t there be harsh consequences for the ecosystem? After all, mosquitos have been on the planet for about 100 million years and represent 3,500 species. As it turns out, mosquitos wouldn’t really be missed if they were to disappear (http://www.nature.com/news/2010/100721/pdf/466432a.pdf). While mosquitos can act as pollinators as well as a food source for other animals, their absence would be merely a temporary setback before another species filled the niche. Of course, there is a gamble in assuming the replacement organism would be harmless.

“Malaria is debilitating and often fatal and we need to find new ways of tackling it. We think our innovative approach is a huge step forward. For the very first time, we have been able to inhibit the production of female offspring in the laboratory and this provides a new means to eliminate the disease,” Crisanti explained.

Each year, sub-Saharan Africa loses about $12 billion in economic productivity due to malarial infections. Considering developed areas in these countries have per capita incomes of about US$1500, this would have very real implications for the quality of life for people in those areas. Eliminating that disease would also allow doctors and hospitals to address other health concerns, and the environment would likely benefit from not having to use insecticides.

http://www.iflscience.com/health-and-medicine/gm-mosquitos-could-eradicate-wild-populations-only-producing-male-offspring

The genome of the termite has just been sequenced, and it is revealing several clues about how the pests create their rigid social order.

For instance, the new genome, detailed today (May 20) in the journal Nature Communications, uncovers some of the underpinnings of termites’ caste system, as well as the roots of the males’ sexual staying power.

Like other social insects— such as ants, honeybees and some wasps — termites live in highly structured “caste systems,” with each creature programmed to perform a rigidly defined job. A select few termite kings and queens reproduce, while drones and soldiers work, defend the colony or care for young.

Yet termites evolved their social structure independently from ants and bees, which belong to an order known as Hymenoptera.

To understand how this happened, Jürgen Liebig, a behavioral biologist at Arizona State University, and his colleagues collected dampwood termites(Zootermopsis nevadensis nuttingi) that lived in Monterey, California. The researchers then sequenced the genome of the insects and measured how those genes were expressed, or turned on and off.

The research revealed several insights about termite sexual and social behavior.

Termite society is roughly half males and half females. Termites have sexually active kings as well as queens, and kings make sperm throughout their lifetimes. Dampwood termite males also have testes that shrivel and grow seasonally.

Ants and honeybees, in contrast, live in predominantly female societies, and ant sex is a one-time affair.

“Their societies generally consist of females — the males are only there to fly out, mate and die,” Liebig told Live Science.

Sure enough, the termites had more gene variants associated with sperm production and degradation, and those genes were expressed to a greater extent than in ants, Liebig said. That finding suggested those genetic differences contributed to male termites’ sexual longevity.

The termite genome also contains a high fraction of genes that are turned off by chemical tags, or methyl groups, the researchers found. In honeybees, this process of methylation sets the fate of individual animals, determining their place in the caste system. The new findings suggest a similar process may be at play in termites.

In addition, both ants and termites communicate via chemical smell signals sensed by receptors on their antennas.

But while ants venture out for food, these particular termites spend their whole lives dining on one piece of wood.

The new analysis revealed that the termites have far fewer cell types for recognizing individual chemicals, probably because they rarely face off against foreign termites or search for food. They simply don’t need to recognize as many smells, Liebig said.

However, some termite species, such as Australian mound-building termites, do forage and encounter foreigners along the way, so as a follow-up, the team would like to see if those termites can detect a greater array of chemicals, Liebig said.

http://www.scientificamerican.com/article/termite-genome-reveals-details-of-caste-system/

Tastes are a privilege. The oral sensations not only satisfy foodies, but also on a primal level, protect animals from toxic substances. Yet cetaceans—whales and dolphins—may lack this crucial ability, according to a new study. Mutations in a cetacean ancestor obliterated their basic machinery for four of the five primary tastes, making them the first group of mammals to have lost the majority of this sensory system.

The five primary tastes are sweet, bitter, umami (savory), sour, and salty. These flavors are recognized by taste receptors—proteins that coat neurons embedded in the tongue. For the most part, taste receptor genes present across all vertebrates.

Except, it seems, cetaceans. Researchers uncovered a massive loss of taste receptors in these animals by screening the genomes of 15 species. The investigation spanned the two major lineages of cetaceans: Krill-loving baleen whales—such as bowheads and minkes—were surveyed along with those with teeth, like bottlenose dolphins and sperm whales.

The taste genes weren’t gone per se, but were irreparably damaged by mutations, the team reports online this month in Genome Biology and Evolution. Genes encode proteins, which in turn execute certain functions in cells. Certain errors in the code can derail protein production—at which point the gene becomes a “pseudogene” or a lingering shell of a trait forgotten. Identical pseudogene corpses were discovered across the different cetacean species for sweet, bitter, umami, and sour taste receptors. Salty tastes were the only exception.

“The loss of bitter taste is a complete surprise, because natural toxins typically taste bitter,” says zoologist Huabin Zhao of Wuhan University in China who led the study. All whales likely descend from raccoon-esque raoellids, a group of herbivorous land mammals that transitioned to the sea where they became fish eaters. Plants range in flavors—from sugary apples to tart, poisonous rhubarb leaves—and to survive, primitive animals learned the taste cues that signal whether food is delicious or dangerous. Based on the findings, taste dissipated after this common ancestor became fully aquatic—53 million years ago—but before the group split 36 million years ago into toothed and baleen whales.

“Pseudogenes arise when a trait is no longer needed,” says evolutionary biologist Jianzhi Zhang of the University of Michigan, Ann Arbor, who was not involved in the study. “So it still raises the question as to why whales could afford to lose four of the five primary tastes.” The retention of salty taste receptors suggests that they have other vital roles, such as maintaining sodium levels and blood pressure.

But dulled taste perception might be dangerous if noxious substances spill into the water. Orcas have unwittingly migrated into oil spills, while algal toxins created by fertilizer runoff consistently seep into the fish prey of dolphins living off the Florida coast.

“When you have a sense of taste, it dictates whether you swallow or not,” says Danielle Reed, a geneticist at the Monell Chemical Senses Center in Philadelphia, Pennsylvania. She was not involved with the current work, but co-authored a 2012 paper that found the first genetic inklings that umami and sweet taste receptors were missing in cetaceans, albeit in only one species—bottlenose dolphins.

Flavors are typically released by chewing, but cetaceans tend to swallow their food whole. “The message seems clear. If you don’t chew your food and prefer swallowing food whole, then taste really becomes irrelevant,” Reed says.

http://news.sciencemag.org/biology/2014/05/whales-cant-taste-anything-salt

Thanks to Dr. Rajadhyaksha for bringing this to the attention of the It’s Interesting community.


Workflow for 3D face scan processing, including the A) original surface, B) trimmed to exclude non-face parts, C) reflected to make mirror image, D) anthropometric mask of quasi-landmarks, E) remapped, F) reflected remapped, G) symmetrized and H) reconstructed.

By Philip Ross

Could a single hair be used to make an accurate 3D model of a criminal suspect’s face? Researchers from the U.S. and Belgium have developed a computer program that renders a crude genetic “mugshot” from a small sample of DNA.

Forensics can already predict eye and hair color relatively easily. Io9 notes that criminal investigators can even use maggots to extract a victim’s DNA from their unidentifiable body or find hidden faces by zooming into hi-res photos of eyes. But the face is a complex structure that’s more difficult to map from just one DNA sample.

According to New Scientist, researchers used a stereoscopic camera to make 3D images of roughly 600 volunteers with mixed European and West African ancestry. They identified more than 7,000 distinct points on the face to see how sex and racial ancestry affect the position of these points. The variations were used to develop a statistical model that reconstructs the overall shape of a person’s face.

The team also isolated 24 genetic variants, called single nucleotide polymorphisms, which play a role in shaping a face, such as those that shape the head during embryonic development. Lastly, researchers had volunteers rate the 600 faces on perceived ethnicity as well as on a scale of masculinity and femininity.

The new study, published in the journal PLOS Genetics, says this process could allow investigators to make computer-generated mugshots from genetic material left at a crime scene.

“We show that facial variation with regard to sex, ancestry, and genes can be systematically studied with our methods, allowing us to lay the foundation for predictive modeling of faces,” the authors note. “Such predictive modeling could be forensically useful; for example, DNA left at crime scenes could be tested and faces predicted in order to help to narrow the pool of potential suspects. Further, our methods could be used to predict the facial features of descendants, deceased ancestors, and even extinct human species. In addition, these methods could prove to be useful diagnostic tools.”

Any 3D renderings created using the new technology wouldn’t be used in a court of law – any person identified via the DNA mugshots would still have his DNA compared to the crime scene sample – but it could at least narrow the search for a suspected criminal. And there are still a few kinks to work out in the process before the technology is ever used in the field.

“I believe that in five to 10 years’ time, we will be able to computationally predict a face,” Peter Claes of the Catholic University of Leuven in Belgium told New Scientist.

http://www.ibtimes.com/dna-mugshot-how-crime-fighting-computer-sketch-program-can-predict-face-your-genes-1563049

Thanks to Da Brayn for bringing this to the attention of the It’s Interesting community.