Daily Archives: July 27, 2017

I

n a step that some of the nations leading scientists have long warned against and that has never before been accomplished, biologists in Oregon have edited the DNA of viable human embryos efficiently and apparently with few mistakes, according to a report in Technology Review.

The experiment, using the revolutionary genome-editing technique CRISPR-Cas9, was led by Shoukhrat Mitalipov of Oregon Health and Science University. It went beyond previous experiments using CRISPR to alter the DNA of human embryos, all of which were conducted in China, in that it edited the genomes of many more embryos and targeted a gene associated with a significant human disease.

This is the kind of research that is essential if we are to know if its possible to safely and precisely make corrections in embryos DNA to repair disease-causing genes, legal scholar and bioethicist R. Alta Charo of the University of Wisconsin, Madison, told STAT. While there will be time for the public to decide if they want to get rid of regulatory obstacles to these studies, I do not find them inherently unethical. Those regulatory barriers include a ban on using National Institutes of Health funding for experiments that use genome-editing technologies in human embryos.

advertisement

The firstexperiment using CRISPR to alter the DNA of human embryos, in 2015, used embryos obtained from fertility clinics that had such serious genetic defects they could never have developed. In the new work, Technology Review reported, Mitalipov and his colleagues created human embryos using sperm donated by men with the genetic mutation that they planned to try to repair with CRISPR. The embryos are described as clinical quality. A 2017 experiment, also in China, used CRISPR to edit DNA in normal, presumably viable fertilized eggs, or one-cell human embryos.

Also in contrast to the experiments in China, those led by Mitalipov reportedly produced very few off-target effects, or editing of genes that CRISPR was supposed to leave alone. And the experiment avoided what is called mosaicism, in which only some cells of an embryo have the intended DNA changes. The embryos were not allowed to develop beyond a very early stage.

Because changing the DNA of an early embryo results in changes to cells that will eventually produce sperm and eggs, if the embryo is born and grows to adulthood, any children he or she has will inherit the genetic alteration, which is called germline editing. That has led to fears that such manipulations could alter the course of human evolution.

It has also triggered warnings about designer babies, in which parents customize their IVF embryos by adding, removing, or changing genes for certain traits.

A recent report on genome-editing from the National Academies did not call for a moratorium on research into germline editing, arguing that it might one day be a way for some parents to have healthy, biological children, such as when both mother and father carry genetic mutations that cause severe diseases.

But we anticipated that there would need to be a lot of research to see if you could make these changes without any unintentional effects,said Charo, who co-chaired the Academies committee. Mitalipov, who did not respond to requests for comment, has now shown that the answer to that might be yes.

Some scholars questioned how important the new study is, however. Stanford University law professor and bioethicist Hank Greely tweeted that the key point is that no one has tried to implant any edited embryos. Research embryos that are not to be transferred for possible implantation are not a big deal, he argued.

This story has been updated with additional comments by experts and details of similar experiments.

Senior Writer, Science and Discovery

Sharon covers science and discovery.

Trending

AstraZeneca lung cancer immunotherapy trial failure sends shares plunging

AstraZeneca lung cancer immunotherapy trial failure sends shares plunging

Trump says its too expensive to care for transgender

Trump says its too expensive to care for transgender service members. Heres the truth

Scientists build DNA from scratch to alter lifes blueprint

Scientists build DNA from scratch to alter lifes blueprint

Recommended

How a teens skin cells, transformed into a beating

How a teens skin cells, transformed into a beating model of a heart, have spurred research

DEA solicited applications to grow marijuana for research. It

DEA solicited applications to grow marijuana for research. It hasnt approved one

This biotech aims to transform the diagnosis of mental

This biotech aims to transform the diagnosis of mental illness. Michael Phelps backs it. Can it

Read more:
Using CRISPR, scientists efficiently edit genome of viable human embryos - STAT

Freshwater alga in the genus Zygnema would be one target of sequencing project.

Norbert Hlsmann/Flickr (CC BY-NC-SA 2.0)

By Dennis NormileJul. 27, 2017 , 8:00 AM

Hopes of sequencing the DNA of every living thing on earth are taking a step forward with the announcement of plans to sequence at least 10,000 genomes representing every major clade of plants and eukaryotic microbes. Chinese sequencing giant BGI and the China National Genebank (CNGB) held a workshop yesterday on the sidelines of the International Botanical Congress, being held this week in BGI's hometown of Shenzhen, to discuss what they are calling the 10KP plan. About 250 plant scientists participated in the discussions and "are raring to go," says Gane Ka-Shu Wong, a genomicist and bioinformaticist at University of Alberta in Edmonton.

The 10KP plan will be a key part of the Earth BioGenome Project (EBP), an ambitious and still evolving scheme to get at least rough sequence data on the 1.5 million eukaryotic species, starting with detailed sequences of one member of each of the 9000 eukaryotic families. The effort to sequence plants is moving ahead a bit faster than other aspects of EBP "because plant scientists are more collaborative," Wong says jokingly.

The 10KP plan is also building on a previous 1,000 plant (1KP) transcriptome project. That effort, launched in 2012 and now nearing completion, was also led by BGI, where Wong is an associate director.

"One thing we focused on (for 1KP) was sampling phylogenetic diversity, not just crops and model organisms," Wong says. That strategy will continue with 10KP. The transcriptome project has resulted in more than 50 papers, with the overall summary publication still to come. A lot of the analysis has focused on plant evolution. One surprise was that important transcription factors previously thought to have evolved as land plants colonized terrestrial habitats can actually be traced back to green algae, says Michael Melkonian, a botanist at the University of Cologne in Germany. Screening green algae also turned up new light-sensitive proteins that neuroscientists now use to study how different neurons interact and better understand neurological functioning.

Whereas the 1KP project only tackled the transcriptome, or all the messenger RNA expressed by an organism, 10KP will produce completely new sequences of the entire genome. And scientists expect an even larger bonanza of fundamental insights and economic spin-offs. The 10KP project "is 1KP on steroids," says Douglas Soltis, a plant biologist at the Florida Museum of Natural History at the University of Florida in Gainesville. He adds that one "wonderful thing" about the project is that it will provide reference genomes for "the numerous plant researchers studying non-model systems," he says. The project will also present "an unprecedented opportunity to address fundamental questions about plant evolution," says Stephen Smith, an evolutionary biologist at the University of Michigan, Ann Arbor. Study targets are expected to include the role of genome duplication, the correlation between genomic and morphological changes, and how rates of evolution changed over time.

We're ready to start sequencing yesterday.

One challenge Smith points to is the need to develop new means of analyzing and synthesizing sequencing information. "Existing tools and methods are unable to handle the extraordinary scale of the data," he says. Wong says another bottleneck will be dealing with the paperwork needed to comply with legal requirements of shipping plant material across borders, as well as complying with the Nagoya Protocol, an international pact that seeks to ensure the fair and equitable sharing of genetic resources. On the other hand, gathering specimens is easier than for other areas of genetics. "You don't have to chase down some animal, you can usually just go to a botanical garden," Wong says.

Xu Xun, who leads technical development for BGI, says the company and CNBG will cover the sequencing costs but "scientists will have to find their own funding for collecting samples and for analysis." As for timing, Wong says they hope to gather the samples in the next two years and "we hope to wrap up the sequencing and analysis in 5 years."

"We're ready to start sequencing yesterday," Wong says. And plant scientists are eager. After the meeting yesterday in Shenzhen, "several people came up people already wanting to send samples," he says.

Follow this link:
Plant scientists plan massive effort to sequence 10000 genomes - Science Magazine

July 27, 2017 by Bob Yirka report A depiction of the double helical structure of DNA. Its four coding units (A, T, C, G) are color-coded in pink, orange, purple and yellow. Credit: NHGRI

(Phys.org)A large international team of researchers has developed a Danish reference genome catalog based on the de novo assembly of 150 genomes sequenced from 50 family trios. In their paper published in the journal Nature, the group describes the multi-year effort, its purpose, and where they believe such efforts are leading.

One of the ways that scientists are learning about diseases, particularly those that are hereditary in nature, is by sequencing the genomes of large groups of peopledoing so enables searching for variants that cause or contribute to a given diseasethe ultimate goal would be to sequence every single person on Earth. In this new effort, the researchers have sequenced the genomes of 150 people in Denmark (from 50 family trios) of Danish descentnative Inuits and immigrants were screened out.

The effort, the researchers report, was carried out partly to create a Danish reference catalog and partly to learn how to conduct large-scale genome sequencing. They note that such a project required the combined efforts of multiple people and organizations working in coordinated fashion. Ultimately, the project cost approximately $10 million.

One major aspect of the project was selecting technology and determining how many people to sequence. The team wound up using samples from 50 families and did the sequencing using both combinations of paired-end and mate-pair libraries with the Illumina HiSeq2000. They note also that de novo assemblies were used because the researchers believed other approaches left out pertinent information. De novo refers to deriving a peptide sequence from a mass spectrum without the use of a sequence database. It is the preferred approach to sequencing when the aim is to identify novel peptides in organisms that have not been previously sequenced. The researchers report very few gaps in the data. They also note that three assemblies were used: Allpaths-LG14, SOAPdenovo2 and SGA. Accuracy was measured by comparing their results with the human reference genome.

The researchers hope that their effort will lead to improved medical interpretation of genetics in Denmark.

Explore further: Genome sequencing of individual Korean offers opportunity to identify parts of sequence unique to Korean population

More information: Lasse Maretty et al. Sequencing and de novo assembly of 150 genomes from Denmark as a population reference, Nature (2017). DOI: 10.1038/nature23264

Abstract Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set of structural variants including many novel insertions and demonstrate how this variant catalogue enables further deciphering of known association mapping signals. We leverage the assemblies to provide 100 completely resolved major histocompatibility complex haplotypes and to resolve major parts of the Y chromosome. Our study provides a regional reference genome that we expect will improve the power of future association mapping studies and hence pave the way for precision medicine initiatives, which now are being launched in many countries including Denmark.

Journal reference: Nature

2017 Phys.org

(Phys.org)A team of researchers with the Genomic Medicine Institute at Seoul National University in South Korea and Korean genetic sequencing firm Macrogen has conducted the most complete genome sequencing of a person ...

(Medical Xpress)Via genetic analysis, a large international team of researchers has found rare, damaging gene variants that they believe contribute to the risk of a person developing schizophrenia. In their paper published ...

(Phys.org) Genome sequencing-technology company, Illumina, based in San Diego has announced (at the annual JP Morgan Healthcare Conference) that its new machine, called the HiSeq X Ten is able to sequence whole human genomes ...

A team spanning Baylor College of Medicine, Rice University, Texas Children's Hospital and the Broad Institute of MIT and Harvard has developed a new way to sequence genomes, which can assemble the genome of an organism, ...

Researchers from BGI reported the most complete haploid-resolved diploid genome (HDG) sequence based on de novo assembly with NGS technology and the pipeline developed lays the foundation for de novo assembly of genomes with ...

To reconstruct phylogenetic trees from next-generation sequencing data using traditional methods requires a time-consuming combination of bioinformatic procedures including genome assembly, gene prediction, orthology identification ...

(Phys.org)A large international team of researchers has developed a Danish reference genome catalog based on the de novo assembly of 150 genomes sequenced from 50 family trios. In their paper published in the journal Nature, ...

When salmon spawn, the sperm of competing males are in an all-or-nothing race to be the first to reach and fertilise the eggs.

Malaria was already widespread on Sardinia by the Roman period, long before the Middle Ages, as indicated by research at the Institute of Evolutionary Medicine of the University of Zurich with the help of a Roman who died ...

A new mathematical model of ecology created by University of Chicago scientists provides the most accurate reproduction to date of natural biodiversity, according to a new paper in the journal Nature.

It might seem like a tomato plant and a subway system don't have much in common, but both, it turns out, are networks that strive to make similar tradeoffs between cost and performance.

Bacteria come in all shapes and sizessome are straight as a rod, others twist like a corkscrew. Shape plays an important role in how bacteria infiltrate and attack cells in the body. The helical shape of Helicobacter pylori, ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Continued here:
Researchers conduct sequencing and de novo assembly of 150 genomes in Denmark - Phys.Org