Category Archives: Genome

Above: The genomes of these twin infant macaques were modified with multiple mutations.

The ability to create primates with intentional mutations could provide powerful new ways to study complex and genetically baffling brain disorders.

The use of a genome-tool to create two monkeys with specific genetic mutations.

The ability to modify targeted genes in primates is a valuable tool in the study of human diseases.

By Christina Larson

Until recently, Kunming, capital of Chinas southwestern Yunnan province, was known mostly for its palm trees, its blue skies, its laid-back vibe, and a steady stream of foreign backpackers bound for nearby mountains and scenic gorges. But Kunmings reputation as a provincial backwater is rapidly changing. On a plot of land on the outskirts of the citywilderness 10 years ago, and today home to a genomic research facilityscientists have performed a provocative experiment. They have created a pair of macaque monkeys with precise genetic mutations.

Last November, the female monkey twins, Mingming and Lingling, were born here on the sprawling research campus of Kunming Biomedical International and its affiliated Yunnan Key Laboratory of Primate Biomedical Research. The macaques had been conceived via in vitro fertilization. Then scientists used a new method of DNA engineering known as CRISPR to modify the fertilized eggs by editing three different genes, and they were implanted into a surrogate macaque mother. The twins healthy birth marked the first time that CRISPR has been used to make targeted genetic modifications in primatespotentially heralding a new era of biomedicine in which complex diseases can be modeled and studied in monkeys.

CRISPR, which was developed by researchers at the University of California, Berkeley, Harvard, MIT, and elsewhere over the last several years, is already transforming how scientists think about genetic engineering, because it allows them to make changes to the genome precisely and relatively easily (see Genome Surgery, March/April). The goal of the experiment at Kunming is to confirm that the technology can create primates with multiple mutations, explains Weizhi Ji, one of the architects of the experiment.

Ji began his career at the government-affiliated Kunming Institute of Zoology in 1982, focusing on primate reproduction. China was a very poor country back then, he recalls. We did not have enough funding for research. We just did very simple work, such as studying how to improve primate nutrition. Chinas science ambitions have since changed dramatically. The campus in Kunming boasts extensive housing for monkeys: 75 covered homes, sheltering more than 4,000 primatesmany of them energetically swinging on hanging ladders and scampering up and down wire mesh walls. Sixty trained animal keepers in blue scrubs tend to them full time.

The lab where the experiment was performed includes microinjection systems, which are microscopes pointed at a petri dish and two precision needles, controlled by levers and dials. These are used both for injecting sperm into eggs and for the gene editing, which uses guide RNAs that direct a DNA-cutting enzyme to genes. When I visited, a young lab technician was intently focused on twisting dials to line up sperm with an egg. Injecting each sperm takes only a few seconds. About nine hours later, when an embryo is still in the one-cell stage, a technician will use the same machine to inject it with the CRISPR molecular components; again, the procedure takes just a few seconds.

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Genome Editing

Energun - Mutation of the Genome
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Energun - Mutation of the Genome - Video

A genetic disease has been cured in living, adult animals for the first time using a revolutionary genome-editing technique that can make the smallest changes to the vast database of the DNA molecule with pinpoint accuracy.

Scientists have used the genome-editing technology to cure adult laboratory mice of an inherited liver disease by correcting a single "letter" of the genetic alphabet which had been mutated in a vital gene involved in liver metabolism.

A similar mutation in the same gene causes the equivalent inherited liver disease in humans - and the successful repair of the genetic defect in laboratory mice raises hopes that the first clinical trials on patients could begin within a few years, scientists said.

The success is the latest achievement in the field of genome editing. This has been transformed by the discovery of Crispr, a technology that allows scientists to make almost any DNA changes at precisely defined points on the chromosomes of animals or plants. Crispr pronounced "crisper" was initially discovered in 1987 as an immune defence used by bacteria against invading viruses. Its powerful genome-editing potential in higher animals, including humans, was only fully realised in 2012 and 2013 when scientists showed that it can be combined with a DNA-sniping enzyme called Cas9 and used to edit the human genome.Scientists have used the genome-editing technology to cure adult laboratory mice of an inherited liver disease by correcting a single "letter" of the genetic alphabet which had been mutated in a vital gene involved in liver metabolism.

A similar mutation in the same gene causes the equivalent inherited liver disease in humans - and the successful repair of the genetic defect in laboratory mice raises hopes that the first clinical trials on patients could begin within a few years, scientists said.

The success is the latest achievement in the field of genome editing. This has been transformed by the discovery of Crispr, a technology that allows scientists to make almost any DNA changes at precisely defined points on the chromosomes of animals or plants. Crispr pronounced "crisper" was initially discovered in 1987 as an immune defence used by bacteria against invading viruses. Its powerful genome-editing potential in higher animals, including humans, was only fully realised in 2012 and 2013 when scientists showed that it can be combined with a DNA-sniping enzyme called Cas9 and used to edit the human genome.

Since then there has been an explosion of interest in the technology because it is such a simple method of changing the individual letters of the human genome the 3 billion "base pairs" of the DNA molecule with an accuracy equivalent to correcting a single misspelt word in a 23-volume encyclopaedia.

In the latest study, scientists at the Massachusetts Institute of Technology (MIT) used Crispr to locate and correct the single mutated DNA base pair in a liver gene known as LAH, which can lead to a fatal build-up of the amino acid tyrosine in humans and has to be treated with drugs and a special diet.

The researchers effectively cured mice suffering from the disease by altering the genetic make-up of about a third of their liver cells using the Crispr technique, which was delivered by high-pressure intravenous injections.

"We basically showed you could use the Crispr system in an animal to cure a genetic disease, and the one we picked was a disease in the liver which is very similar to one found in humans," said Professor Daniel Anderson of MIT, who led the study.

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Revealed: Scientists edit DNA to correct adult genes and cure diseases

Genome structure of T4 phage
For more information, log on to- http://shomusbiology.weebly.com/ this bacteriophage lecture explains the genome structure of T4 bacteriophage. It also expla...

By: Suman Bhattacharjee

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Genome structure of T4 phage - Video

Mind Brain Genome Microbiome - Sages and Scientists
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Mind Brain Genome Microbiome - Sages and Scientists - Video

Breaking Bio Episode 19 (Guest: David Winter)
Originally published: February 24, 2013 ( In episode 19, we dissect the Sasquatch genome paper with David Winter (. Originally published: February 24, 2013 (...

By: Rebekah Saucedo

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Breaking Bio Episode 19 (Guest: David Winter) - Video

Released: 4/17/2014 4:00 PM EDT Source Newsroom: Mayo Clinic Expert Available Contact Information

Available for logged-in reporters only

http://newsnetwork.mayoclinic.org/discussion/national-dna-day-is-april-25-experts-available-for-comment

Newswise ROCHESTER, Minn. April 17, 2014 Friday, April 25, is National DNA Day, the date which commemorates completion of the Human Genome Project, the national effort to identify and decode all 6 billion letters in human DNA. Since that time, medical researchers and practitioners have found new ways to apply genomics for everyone who needs healing, and thanks to staggering technological advancements and next-generation sequencing, the cost to sequence a patients genome has decreased from $3 billion for the first human genome in 2003 to approximately $1,500.

Media: Gianrico Farrugia, M.D., director of the Mayo Clinic Center for Individualized Medicine, is available for interviews and background about the future of genomic medicine, as well as information about the latest practices and transformative clinical trials. To interview Dr. Farrugia contact Sam Smith, Mayo Clinic Public Affairs, 507-284-5005, newsbureau@mayo.edu. To view genome sequencing animation, visit the Mayo Clinic News Network.

Suggested topics for Dr. Farrugia to discuss:

Medicine Meant for Me: Genetic tests to determine drug efficacy are an important new tool physicians can use to tailor health care. Mayo Clinic and other medical centers are embedding this information in patients electronic medical records to help prevent adverse drug reactions. One in a Billion: Each persons genetic code has roughly 6 billion letters of DNA code. Technological advances have accelerated the ability to read and interpret this data, helping patients with rare or completely unknown genetic conditions find answers, giving peace of mind to their families. Patient cases are available. Cancers Worst Enemy: Mayo Clinic is conducting several leading-edge studies around cancer, including taking breast cancer cells from women who have a high risk of recurrence and growing tumors outside their bodies to develop and test new targeted therapies. Mayo Clinic is the only institution to sequence tumor and normal genomes before, in the middle of and after chemotherapy.

Ten facts about DNA and genomics in medicine:

1. There are 31 markers commonly used in cancer care, according to the National Cancer Institute. Using new sequencing technologies, researchers can identify hundreds of markers in individual tumors within a few days. 2. There are more than 7,000 diseases considered rare in the U.S., most of which have some genomic or inherited component, according to the National Organization of Rare Disorders. 3. The Food and Drug Administration lists 155 drugs known to have sensitivity to individual genomic makeup. That number is expected to increase dramatically as sequencing drives rapid discovery. 4. DNA stands for deoxyribonucleic acid. 5. There are approximately 6 billion letters in the average human genome. 6. Spelled out, each persons genome would fill 1,000 New York City telephone books. 7. Nearly all of the roughly 25 trillion cells in the human body have identical sets of DNA contained in the cell nucleus. 8. When uncoiled, the DNA contained in every cell nucleus measures about 6 feet in length. 9. It took about 10 years and cost nearly $3 billion to sequence the first human genome. It can now be done in a few days for roughly $1,500. 10. All humans are about 99.9 percent identical. Less than 0.1 of 1 percent makes us individuals.

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National DNA Day is April 25; Experts Available for Comment

The Harvard-MIT genomic science institute stays mute on how it will assert control over the tools expected to speed cures and change gene therapy.

One of the most important genetic technologies developed in recent years is now patented, and researchers are wondering what they will and wont be allowed to do with the powerful method for editing the genome.

On Tuesday, the Broad Institute of MIT and Harvard announced that it had been granted a patent covering the components and methodology for CRISPRa new way of making precise, targeted changes to the genome of a cell or an organism. CRISPR could revolutionize biomedical research by giving scientists a more efficient way of re-creating disease-related mutations in lab animals and cultured cells; it may also yield an unprecedented way of treating disease (see Genome Surgery).

The patent, issued just six months after its application was filed, covers a modified version of the CRISPR-Cas9 system found naturally in bacteria, which microbes use to defend themselves against viruses. The patent also covers methods for designing and using CRISPRs molecular components.

The inventor listed on the patent is Feng Zhang, an MIT researcher and core faculty member of the Broad. Zhang was an MIT Technology Review Innovator Under 35 in 2013.

The patent describes how the tools could be used to treat diseases, and lists many specific conditions from epilepsy, to Huntingtons, to autism, and macular degeneration. One of the most exciting possibilities for CRISPR is its potential to treat genetic disorders by directly correcting mutations on a patients chromosomes. That would enable doctors to treat diseases that cannot be addressed by more traditional methods, a goal already set by a startup cofounded by Zhang called Editas Medicine (see New Genome-Editing Method Could Make Gene Therapy More Precise and Effective).

Another founder of Editas, Jennifer Doudna, and her institute, the University of California, have a pending patent application for CRISPR technology. How that west coast application will be affected is not yet clear. Its also unclear what impact the Broads claims on the technology will have on its commercial use and on basic research.

Chelsea Loughran, an intellectual property litigation lawyer who has been following CRISPR over the last year, says that lots of people are already using CRISPR and its not clear if it will now become harder for them to do that. All of that is in the hands of MIT and the Broad, she says.

While MIT, Harvard, and the Broad all jointly own the CRISPR patents announced yesterday, the Broads technology licensing office is managing decisions about who will get licenses to use the technology, says Lita Nelsen, director of the MIT Technology Licensing Office. (Licenses areformal permissions to use a patented technology, often in exchange for money.)

A spokesperson for the Broad says that specific details around licensing arent available at this time, but the Broad does intend to make this technology broadly available to scientists.

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CRISPR Genome Editing Technology Patent

Symptoms of Down syndrome are produced by gene impairments across every chromosome, not just one, according to a study that may bring new understanding to the most common genetic cause of intellectual disability.

Down syndrome occurs when there is an extra copy of chromosome 21, a condition called trisomy 21. In a study of twins, where only one had Down syndrome, a genomic analysis found that gene expression in the affected sibling had been altered throughout the genome.

Researchers have presumed for decades that Down syndrome is mainly caused by the overabundance of effects of chromosome 21 genes. The findings, published today in the journal Nature, show that a third copy of chromosome 21 disturbs the expression of all DNA in the genome. The surprise result may change understanding of Down syndromes symptoms, as well as other disorders caused by abnormal numbers of chromosomes, said Stylianos Antonarakis, a study author.

The results of this study complicate the understanding of molecular mechanisms of the symptoms of trisomy 21 and opens a new hypotheses for all chromosomal abnormalities, said Antonarakis, chairman of the Department of Genetic Medicine and Development at the University of Geneva Medical School in Switzerland, in an e-mail.

About 6,000 U.S. babies are born with Down syndrome each year. In addition to cognitive impairment, people with the condition may also suffer from ailments including heart defects, low muscle tone, vision and hearing problems and early onset Alzheimers disease. There is no cure.

The study compared a single set of identical twins in which just one twin had an extra chromosome 21. This unusual situation enabled researchers to study the effects of chromosome 21 without the bias of genome variability.

While gene expression has been studied extensively in Down syndrome, natural variations among individuals concealed the genome-wide effect of chromosome 21, researchers said.

The study found that gene dysregulation, or impairment, seen in the twin with Down syndrome is organized in domains or territories along all the different chromosomes.

Thus trisomy 21 could be now viewed as a general genomic disorder, and genes throughout the genome could be involved in the different signs and symptoms, Antonarakis said.

Humans normally have 46 chromosomes in each cell, divided into pairs. Chromosome 21 is the smallest human chromosome, accounting for less than 2 percent of the genome. Chromosome 21 probably contains 200 to 300 genes that provide instructions for making proteins.

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Down Syndrome Cause Revised by Study on Genome Effects

The Genome Project - Methylated Buoy
The Genome Project @ Ryans Bar, Stoke Newington - Nicks 40th Birthday 050414 - Julian Newton Photography.

By: Chris Jones

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