Monthly Archives: March 2015

Small DNA changes separate chimp and human brains

Posted: March 10, 2015 at 3:45 am

Modern humans share about 95% of their genetic code with chimpanzees. Yet human brains, and what we do with them, are vastly different.

In the decade since the human genome was mapped, researchers have identified hundreds of small regions that differ between humans and fellow primates. Many show evidence of accelerated changes that might offer evolutionary clues to such fundamental differences as skeletal structure, motor skills and cognition since our human ancestors parted ways with chimpanzees some 6 million years ago.

A new study suggests that just 10 differences on one particular strand of human DNA lying near a brain-development gene could have been instrumental in the explosive growth in the human neocortex.

The DNA region, containing just 1,200 base pairs, is not a gene. But it lies near one that is known to affect early development of the human neocortex, according to the study, published online Thursday inCurrent Biology.

Researchers showed that the region, known as HARE5, acts as an enhancer of the gene FZD8. Embryos of mice altered with human HARE5 developed significantly larger brains and more neurons compared with embryos carrying the chimp version, according to the study.

"It could contribute to making us unique, and making our brains unique, said Duke University developmental neuroscientist Debra Silver, coauthor of the study. Were seeing the human enhancer turn on gene activity right at the onset of when a population of cells called neural stem cells are rapidly proliferating. They shift within a day or two to making neurons.

The type of neurons and the timing of their development are significant -- these excitatory neurons arise later in utero, which is consistent with human fetal brain development patterns driven by the gene in question.

So have they found the genetic missing link between chimp brains and human brains?

"We think its likely that theres many additional accelerated regions that are contributing to human brain development, and they may be impacting other aspects that make our brains unique, Silver said.

It still would be a pretty big gap to go all the way to: Oh, and thats why we have a spoken language, or different types of fine muscle movements or different cognitive abilities,'" said Katherine Pollard, an evolutionary genomics researcher at UC San Francisco's Gladstone Institutes, who was not involved in the study. "But this is certainly a big step in that direction."

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Small DNA changes separate chimp and human brains

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DNA analysis traces African slaves back to their roots

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Maxilla and mandible of one of the three 17th century skeletons from the Caribbean island of St. Martin showing a common type of African dental modification. PNAS/H. Schroeder et. al.

To better understand the complex history of slavery, it helps to know more about the origins of millions of individuals who were shipped from their homes in Africa to plantations in the Caribbean, South America and the United States.

Historians have a good idea that 12 million or so slaves came from West and West-Central Africa between 1500 and 1850. But incomplete and scarce historical records have made it difficult to offer crucial details about the slaves' ethnic origins and the regions from which they were taken.

Now, a team of researchers says they have for the first time used a new DNA technique to fill in these gaps, which could provide further insight into the slave trade.

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Writing in Proceedings of the National Academy of Sciences (PNAS) Monday, researchers led by Hannes Schroeder of the Centre for GeoGenetics at the University of Copenhagen described how they used whole genome capture to retrieve the DNA from 400-year-old skeletal remains of three slaves, known as the Zoutsteeg Three.

"There are historical records - merchant ledgers, shipping records and the like - but they tend to refer to coastal shipping points rather than the slaves' actual ethnic or geographic origins. This is where the DNA comes in," Schroeder said. "It can provide new insights where historical information is missing. In that way, DNA is simply another type of archive that we can use to study the past."

Schroeder and his team analyzed the DNA from teeth recovered from a construction site on the Caribbean island of Saint Martin back in 2010. They then used a different technique known as principal component analysis to compare that DNA with 11 modern West African reference populations. From that, they were able to conclude the individuals most likely came from Bantu-speaking groups in northern Cameroon and non-Bantu-speaking communities living in present-day Nigeria and Ghana.

When they were first uncovered, the remains of the three slaves were dated back to the 17th century by way of shards of pottery and other artifacts found at the site. It was also determined they were most likely slaves, given the time period and the fact their teeth had been filed, a common custom among Africans then.

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Hernandez's attorney continues to challenge DNA evidence

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FALL RIVER, Mass. Shortly before embarking on a journey that ended in an alleged murder of Odin Lloyd, Aaron Hernandez walked through his family room with a black object in his hands an object prosecutors claim was a pistol.

Jurors in Hernandezs murder trial got a view of that moment Monday when prosecutors played a number of clips from the video surveillance system in the former NFL stars home. And the one that garnered the most attention in the courtroom was captured shortly before 1 a.m. on June 17, 2013.

In it, Hernandez walks through his family room, past his fiance, Shayanna Jenkins, his young daughter and the couples babysitter, Jennifer Fortier.

As Hernandez moves the object from one hand to the other, one of his alleged accomplices, Carlos Ortiz, walks behind him.

A defense attorney suggested in his opening statement that the object was a remote control and lead prosecutor William McCauley tried to refute that while questioning Fortier.

This remote control did you ever see a remote control anywhere in the house that resembled a firearm, a gun? McCauley asked.

Defense attorney Michael Fee immediately objected, and Judge E. Susan Garsh sustained it.

OK, McCauley continued, describe any remote control that you saw in that house.

The only ones Ive ever seen are what I told you earlier, a rectangle, black or gray, she said.

It was impossible to tell from the clip played Monday exactly what Hernandez was holding. However, prosecutors have other shots they allege show Hernandez with the murder weapon, and Judge Garsh has ruled that they can call an official from Glock who has studied the video clips and concluded the object is, in fact, a handgun manufactured by the Swiss company.

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Quick DNA Scans Could Ensure Food Is Safe to Eat

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Foodborne illnesses and food fraud are common, but rapid DNA sequencing can reveal hidden dangers

Tools to analyze DNA in meals, including fish, may soon help eliminate fraudulent claims as to what type of food is being sold or served. Credit: Michael Saechang

An apple can kill, a sprinkle of sprouts can send you to the hospital and your succulent, pan-seared red snapper may actually be tilefish. Despite rising concerns about food safety and authenticity, contamination rates by salmonella, campylobacter, Escherichia coli and other common pathogens have not fallen or are actually on the increase, depending on the microbe, according to a 2013 report from the U.S. Centers for Disease Control and Prevention. Each year foodborne illnesses caused by these microorganisms sicken 48 million Americans, hospitalize 128,000 and kill 3,000, according to the agency.

Food fraud is also increasing. In 2014 Oceana, an international conservation organization, published a two-year study of 1,215 seafood samples and 46 fish types from 674 retailers in 21 states. They found that a third of samples were mislabeled.

Tools to analyze DNA in food items may soon help eliminate these problems. Techniques ranging from whole genome sequencing to the ability to create artificial DNA labels that indicate points of origin are surprisingly affordable now, and have led to novel global collaborations and inventions. Scientists worldwide are working to create databases of foodborne microbial strains, sequence the most common pathogens and tag foods for immediate traceability. The new initiatives promise to speed investigations and reduce foodborne illnesses and deaths; the techniques could also spot food fakery by marketers.

Genome Trakr, a five-year collaboration between the University of California, Davis; Agilent Technologies; and the U.S. Food and Drug Administration, promises to perform whole genome sequencing on a total of 100,000 types of common foodborne pathogens. The technology maps the entire DNA sequence of a microbe, and allows scientists to distinguish one strain from another, allowing fast track-back and earlier elimination of outbreaks around the world. The project began in March 2012 and the database, hosted by the National Center for Biotechnology Information, will be available online and at no cost to researchers and public health officials. The zoom-in detail of a sequenced genome will make it possible to distinguish different strains of a microbe that are otherwise indistinguishable, and trace back a small cluster outbreak before it becomes widespread.

Right now that kind of trace-back is difficult without detailed epidemiologic exposure data. A recent study from Cornell University suggests the new technology is an effective and faster replacement. Using whole genome sequencing, researchers were able to double the number of cases associated with a known 2010 outbreak of a strain of salmonella called salmonella Heidelberg at a long-term care facility in New York City. They even found cases outside the metro region.

Whole genome sequencing has already proved successful in halting serious food outbreaks. In 2012 researchers isolated the specific strain in a salmonella outbreak in tuna sushi that sickened 258 individuals, and tracked it back to a processing plant in India. The U.S. Food and Drug Administration investigated the plant and found 10 sanitation slipups, including four outright violations of safety protocols. In 2014 the FDA was able to halt a U.S. Listeria outbreak that had killed one and sickened seven others. They genotyped and linked the strain to soft Hispanic-style cheeses manufactured by a company called Roos Foods, which ceased all manufacturing after being shut down by the FDA

The gigantic open-access Genome Trakr database should speed up this kind of detective work by providing an enormous volume of data that has already been analyzed. The projects director, U.C. Davis microbiologist Bart Weimer, says that Weve just extended the project to China, and they will map another 10,000 genomes and deposit them. We have other global collaborations pending.

Sequencing a whole genome is only one of the new approaches to food safety, however. Food fraud prevention is also benefitting from a large international project called The International Barcode of Life (iBOL), which is building a genetic library of all life on Earth. Initiated in 2003 by geneticist Paul Hebert at the University of Guelph in Ontario, it offers a global online database of DNA labels, akin to the bar codes on food packaging, for different species. These DNA bar codes are sequences from a small and stable region of the genome, which can reliably be used to identify a species.

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gUIDEbook gRNA Design – for CRISPR genome editing experiments – Video

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gUIDEbook gRNA Design - for CRISPR genome editing experiments
Successful CRISPR genome editing relies on the quality of the gRNA design, and that requires the best bioinformatic software. gUIDEbook from Desktop Genetic...

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Genome study unmasks evolution of Darwin's finches

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A genome study of the famed Darwin finch species on the Galapagos and Cocos islands has unveiled a gene behind the 15 species' remarkable variation of beaks, a feature that helped inspire the father of evolutionary theory.

The study of 120 individual birds from across the South American island chain finds that a single species radiated into more than a dozen others over the past million years, a change fueled by hybridization.

The wide variety of beak shape and size among finches on the archipelago has become an iconic foundational story behind Charles Darwin's "On the Origin of Species," published in 1859 -- even though he misidentified them at first and gave them scant mention in the treatise. But they have come to represent a textbook example of how species develop through random variation and the forces of natural selection.

"He wrote that it looked like this was one species that changed into multiple species, and particularly through the change of the beak shape to utilize food," said Uppsala University geneticist Leif Andersson, co-author of the study published online Wednesday in the journal Nature. "Our data fit perfectly with that.

British biologist Peter and Rosemary Grant, of Princeton University, have spent 40 years studying the subtle changes in the birds, and published a startling example of natural selection unfolding among a pair of species on one of the islands. The two areco-authors of the current report, which used some of the DNA samples they collected.

"You can imagine how satisfying it is for us after all those years in the field to be able to discover a gene that underpins our findings of evolution by natural selection," Peter Grant said.

The gene, called ALX1, is located on a swath of the genome whose coding has been remarkably consistent for ages, until changes altered the production of four proteins, and that gene variation came to dominate.

"As many changes that have occurred over 300 million years have occurred during the last million years on the Galapagos, said Andersson.

The finches are descended from a sharp-billed South American tanager that arrived on the islands about 1.5 million years ago, according to the study. Warbler finches split earliest, about 900,000 years ago, with ground and tree finches constituting the most recent radiation, about 100,000 to 300,000 years ago, according to the study.

But during that time, there was much interbreeding that allowed genes to flow across species, leaving them with a wide variety of beak sizes and shapes, the study suggests.

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Aquatic plant has tiny genome but lots and lots of genes

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BUFFALO, N.Y., Feb. 24 (UPI) -- Bladderworts are a genus of carnivorous plants that prefer freshwater environs or very wet soils. And as a new study finds, at least one bladderwort variety -- in terms of genomics, anyways -- does more with less.

Researchers at the University of Buffalo recently sequenced the genome of Utricularia gibba, one of the most common types of bladderworts called humped or floating bladderwort. Despite its many unique biological features, the quirky aquatic plant has a remarkably short genome.

Inside that short genome are the genetic sequences that enable its odd characteristics. Floating bladderwort forgoes roots, traps prey with vacuum pressure, sprouts small thread-like branches, puts off beautiful yellow flowers and does it all while thriving in aquatic environment.

As the bladderwort's odd lifestyle suggests -- and as the new analysis proved -- a short genome doesn't necessarily translate to a dearth of genetic material. Researchers found that despite its shrunken genome, floating bladderwort boasts more genes than a number of more common plants, including the grape, coffee or papaya plants.

The research suggests that humped bladderwort is more than just economical, it's the opposite of repetitive. It's idiosyncratic -- and especially fluctuant. And it is this variability that allowed the bladderwort to pack so much genetic code into such a small space.

"The story is that we can see that throughout its history, the bladderwort has habitually gained and shed oodles of DNA," study leader Victor Albert, a biologist at Buffalo, explained in a press release. "With a shrunken genome, we might expect to see what I would call a minimal DNA complement: a plant that has relatively few genes -- only the ones needed to make a simple plant. But that's not what we see."

But constantly deleting genes to make up for its genetic replications and adaptations, the floating bladderwort seems have become exceptionally good a ridding itself of junk DNA, sequences that have little to no genetic or biological value.

"When you have the kind of rampant DNA deletion that we see in the bladderwort, genes that are less important or redundant are easily lost," Albert said. "The genes that remain -- and their functions -- are the ones that were able to withstand this deletion pressure, so the selective advantage of having these genes must be pretty high."

"Accordingly, we found a number of genetic enhancements, like the meat-dissolving enzymes, that make Utricularia distinct from other species," Albert added.

While floating bladderwort contains only a small percentage of junk DNA, almost 90 percent of the human genome is made up of throwaway genes.

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Fighting a worm with its own genome

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Hints for how to improve the treatment of parasitic infection might lie within the parasite's own genetic code

IMAGE:Tiny parasitic hookworms infect nearly half a billion people worldwide -- almost exclusively in developing countries -- causing health problems ranging from gastrointestinal issues to cognitive impairment and stunted growth... view more

Credit: Yan Hu/Aroian Lab/UC San Diego

Tiny parasitic hookworms infect nearly half a billion people worldwide--almost exclusively in developing countries--causing health problems ranging from gastrointestinal issues to cognitive impairment and stunted growth in children. By sequencing and analyzing the genome of one particular hookworm species, Caltech researchers have uncovered new information that could aid the fight against these parasites.

The results of their work were published online in the March 2 issue of the journal Nature Genetics.

"Hookworms infect a huge percentage of the human population. Getting clean water and sanitation to the most affected regions would help to ameliorate hookworms and a number of other parasites, but since these are big, complicated challenges that are difficult to address, we need to also be working on drugs to treat them," says study lead Paul Sternberg, the Thomas Hunt Morgan Professor of Biology at Caltech and a Howard Hughes Medical Institute investigator.

Medicines have been developed to treat hookworm infections, but the parasites have begun to develop resistance to these drugs. As part of the search for effective new drugs, Sternberg and his colleagues investigated the genome of a hookworm species known as Ancylostoma ceylanicum. Other hookworm species cause more disease among humans, but A. ceylanicum piqued the interest of the researchers because it also infects some species of rodents that are commonly used for research. This means that the researchers can easily study the parasite's entire infection process inside the laboratory.

The team began by sequencing all 313 million nucleotides of the A. ceylanicum genome using the next-generation sequencing capabilities of the Millard and Muriel Jacobs Genetics and Genomics Laboratory at Caltech. In next-generation sequencing, a large amount of DNA--such as a genome--is first reproduced as many very short sequences. Then, computer programs to match up common sequences in the short strands to piece them into much longer strands.

"Assembling the short sequences correctly can be a relatively difficult analysis to carry out, but we have experience sequencing worm genomes in this way, so we are quite successful," says Igor Antoshechkin, director of the Jacobs Laboratory.

Their sequencing results revealed that although the A. ceylanicum genome is only about 10 percent of the size of the human genome, it actually encodes at least 30 percent more genes--about 30,000 in total, compared to approximately 20,000-23,000 in the human genome. However, of these 30,000 genes, the essential genes that are turned on specifically when the parasite is wreaking havoc on its host are the most relevant to the development of potential drugs to fight the worm.

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Regulating genome-edited crops that (according to current regulations) aren't GMOs

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IMAGE:This is a figure depicting four regulatory models for genome-edited crops. view more

Credit: Araki, M. and Ishii, T./Trends in Plant Science 2015

A survey of rice, wheat, barley, fruit, and vegetable crops found that most mutants created by advanced genetic engineering techniques may be out of the scope of current genetically modified organism (GMO) regulations. In a review of these findings, published in the February 25 issue of the Cell Press journal Trends in Plant Science, two bioethicists from Hokkaido University propose new regulatory models for genome-edited crops and declare a call to action for clarifying the social issues associated with such genetically engineered crops.

"Modern genome editing technology has allowed for far more efficient gene modification, potentially impacting future agriculture," says Tetsuya Ishii, PhD, of Hokkaido University's Office of Health and Safety. "However, genome editing raises a regulatory issue by creating indistinct boundaries in GMO regulations because the advanced genetic engineering can, without introducing new genetic material, make a gene modification which is similar to a naturally occurring mutation."

Under current regulations, a GMO is a living organism that has been altered by a novel combination of genetic material, including the introduction of a transgene. Advanced genetic engineering technologies, including ZFN, TALEN, and CRISPR/Cas9, raise regulatory issues because they don't require transgenes to make alterations to the genome. They can simply pluck out a short DNA sequence or add a mutation to an existing gene.

"Genome editing technology is advancing rapidly; therefore it is timely to review the regulatory system for plant breeding by genome editing," says Dr. Ishii. "Moreover, we need to clarify the differences between older genetic engineering techniques and modern genome editing, and shed light on various issues towards social acceptance of genome edited crops."

In their study, Dr. Ishii and a member of his research staff, Motoko Araki, present four regulatory models in order to resolve the indistinct regulatory boundaries that genome editing has created in GMO regulations. They propose that the most stringent regulation (in which most of the mutants are subject to the regulations, whereas only a portion of deletion and insertion mutants fall outside the regulations) should be initially adopted and gradually relaxed because the cultivation and food consumption of genome-edited crops is likely to increase in the near future.

While policy-level discussions about the regulations of genome-edited organisms are slowly taking place around the world, according to Dr. Ishii, his study will serve as a basis for the conversation with regulatory agencies in the world as well as the Japanese Ministry of the Environment.

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Trends in Plant Science, Araki, M. and Ishii, T.: "Towards social acceptance of plant breeding by genome-editing"

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2015 1st Annual UCLA HBA Healthcare Conference: Lunch Keynote – Peter Diamandis – Video

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2015 1st Annual UCLA HBA Healthcare Conference: Lunch Keynote - Peter Diamandis
Peter H. Diamandis, M.D. X PRIZE Foundation, Chairman CEO Human Longevity Inc. (HLI), Co-Founder Vice-Chairman.

By: UCLA Anderson HBA

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