Genome and DNA.

Article 1: 5 synthetic yeast chromosomes created

By Tia Ghose, Senior Writer | March 9, 2017 02:28pm ET

The world is one step closer to a new synthetic organism.

Scientists have created five synthetic yeast chromosomes and placed them inside yeast cells. The chromosomes are composed of the normal letters, or base pairs, that make up DNA, but the sequence is slightly different from those found naturally in yeast.

The new chromosomes could help answer basic science questions, such as what is the purpose of portions of DNA that don't code for genes; they could also be useful for producing drugs like cancer antibodies on a massive scale, said study co-author Joel Bader, a bioinformatics professor at Johns Hopkins University in Baltimore.   

The findings were published today (March 9) in the journal Science in seven separate papers.  [Unraveling the Human Genome: 6 Molecular Milestones]

Building a genome

In 2010, scientists succeeded in creating the first live organism with a completely synthetic genome, a bacterium called Mycoplasma mycoides. Other labs have tweaked the genes needed for life, creating bacteria with synthetic genomes containing the fewest genes needed for life. In 2014, researchers synthesized the first artificial yeast chromosome. [Infographic: How Scientists Created a Semi-Artificial Life Form]

The new effort is part of a larger project called the Synthetic Yeast Genome Project (Sc2.0), which aims to replace all 16 yeast chromosomes with synthetic versions. Once those synthetic versions are swapped with the natural ones, they could be modified so that the resulting yeast produce industrial chemicals, antibiotics or even tastier fake meat, Bader said.

To construct the synthetic genomes, the teams first looked at computer files containing all the genetic data from natural Baker's yeast. Next, they looked at the designer genomes they hoped to replicate and made changes to the reference genomes in the computer files. From there, the files are chopped up into smaller sequences that correspond to what can be made in the lab.

From there, the team synthesized the individual base pairs, or letters of DNA, in a dish, then used the templates to assemble small fragments of DNA, which were then put together. These slightly larger fragments were then placed in yeast. The yeast cells use a method called homologous recombination to repair damaged DNA, and the team took advantage of this ability to have the cell swap out its real genetic code and replace it with synthetic snippets of DNA. By doing this process over and over, the team eventually replaced the five of the yeast chromosomes with synthetic copies, Bader said.

"One of the amazing things is that we are just putting DNA into the cells, and the yeast cells are organizing it in chromosomes," Bader told Live Science.

This makes the process of creating synthetic chromosomes significantly easier, considering that chromosomes are made up of DNA tightly wound around little spools known as histones, which are also modified by separate chemicals. Because mammalian cells lack homologous recombination, it would likely be trickier to assemble a mammalian chromosome, Bader said.

The synthetic genomes are very similar to the natural ones, but the researchers removed some of the genes they suspect are unneeded. They also removed one of the three-letter sequences that tell the cell to stop reading a snippet of DNA and translating it into a protein, known as a stop codon. The goal is to ultimately repurpose this stop codon to potentially make completely new forms of amino acids, Bader said.

Long-term goals

The team hopes that by creating a completely synthetic yeast, they can answer basic questions about the role of DNA. For instance, there are often repetitive sequences of DNA that many scientists believe are the debris left from viral infections in yeast's past. By deleting these fragments, researchers can effectively test these ideas. Scientists could also build complicated molecules, such as the sugar-tipped antibody proteins used in newer cancer treatments, which normally must be made in expensive mammalian cell cultures, Bader said.

While the new work uses essentially the same gene-assembling techniques as the 2014 project, the development of new computer programs enabled large groups to collaborate on the project, said George Church, a geneticist at Harvard University who is working on a separate synthetic E. coli genome project, called the rE.coli project. He is also working on a project to create humanized pigs that could provide transplants that wouldn't be rejected by the immune system.

In addition, translating the lessons learned in yeast could be a challenge, said Church, who was not involved in the current research.

"Whether we learn from this in the bigger genome-writing projects in pig and human, that remains to be seen," Church told Live Science.

Interestingly, the project used the much-vaunted cut-and-paste editing tool called CRISPR for only 31 genetic changes out of more than 5 million letters assembled in the project. While CRISPR has been promoted as a revolutionary way to make point-by-point edits in the genome, it has a fairly high error rate, of around 50 percent for each change made, Church said.

"If you do 10 of those [CRISPR changes] you have a 1-in-1,000 chance of getting the right thing, and if you do 20 of those you have a 1-in-1-billion chance of getting the right thing," Church said.

Given that, in the future scientists may be more likely to synthesize large swaths of the genome using this technique and then just swap it out, because the overall error rate is lower than making many tiny letter-based changes using CRISPR, Church said. That may be especially true for things like humanized pigs, which scientists know will require many genetic changes, he added.

Article 2 : An online store for information about your genes will make it cheap and easy to learn more about your health risks and predispositions.

by Antonio Regalado

While driving and listening to National Public Radio one day, Justin Kao heard about the discovery of a “sweet tooth gene” that makes you more likely to crave sweets. “Oh my God,” thought Kao, who has always loved cookies. “I would pay $5 to know if I had that.”

Kao is hoping that millions of other people will be just as eager to spend a few bucks for tidbits revealed in their DNA. He is a cofounder of Helix, a San Francisco–based company that last summer secured more than $100 million in a quest to create the first “app store” for genetic information.

Our genomes hold information about our health risks, our physical traits, and whom we’re related to. Yet aside from ancestry tests that provide a limited genetic snapshot, there’s not a mass market for DNA data. Helix is a bet by Kao’s former employer, the buyout firm Warburg Pincus, and Illumina, the leading manufacturer of ultrafast DNA sequencing machines, that what’s been missing is the right business model.

Helix’s idea is to collect a spit sample from anyone who buys a DNA app, sequence and analyze the customers’ genes, and then digitize the findings so they can be accessed by software developers who want to sell other apps. Helix calls the idea “sequence once, query often.” (The company says customers will find these apps on websites and possibly in the Android and Apple app stores.)

With its ties to Illumina, Helix thinks it can decode the most important part of a person’s genome—all 20,000 genes and a few other bits—at a cost of about $100, about one-fifth of what it costs other companies. That’s why Helix can afford its second gambit: to generate and store this type of data for all customers, even if they initially make only one specific genetic query—such as whether they have the sweet tooth gene or a risk for a certain disease. Maybe two guys in a garage will write a $10 app that shows you how old you’ll look in 10 years, or which celebrity you are most closely related to. Kao says the tactic will make genetic information available to consumers “at an unprecedentedly low entry price.”

The engine to power the app store is being assembled a mile from Illumina’s San Diego headquarters, in a building where workmen were still bending sheet metal and laying floor tiles in January. Several miles of data cables strung through the ceiling will be connected to a large farm of sequencing machines, able to process the DNA from a million samples a year. Illumina’s CEO, Jay Flatley, also chairman of Helix, has said it could be the largest sequencing center anywhere.

Helix plans to launch the store this year or next. Customers will control their data by deciding who sees it. There’s even a “nuclear button” to erase every A, G, C, and T. But key details are still being sorted out. Will people be able to download their DNA information and take it elsewhere? Probably, though they might pay extra for the privilege.

One company working with Helix is Good Start Genetics, a startup in Cambridge, Massachusetts, that offers pre-conception testing. These DNA tests tell parents-to-be if they share a risk for passing on a serious genetic condition, such as cystic fibrosis. Jeffrey Luber, Good Start’s head of business development, says it hopes to reach a larger audience with an app that can report a few important risks. As with browsing on Amazon, he thinks, people will discover things they “didn’t know they needed but that [are] targeted to them, and that they want.”

A looming question mark is the U.S. Food and Drug Administration, which has kept close tabs on gene tests and will decide how much information Helix apps can reveal. Right now, says Keith Stewart, director of the Center for Individualized Medicine at the Mayo Clinic, most apps that return real medical information—your chance of cancer, say, not just how much Neanderthal is in your DNA—would need agency approval, or at least a doctor in the loop.

“The bottom line is going to be: What are the regulatory constraints on information that is truly useful?” says Mirza Cifric, CEO of Veritas Genetics. His company has been offering since last fall to sequence a person’s entire genome and is creating its own app to explore the data, complete with a button to get a FaceTime appointment with a genetic counselor. Cifric hasn’t decided whether to create an app with Helix, but he says he shares its core belief: “The genome is an asset that you have for life, and you’ll keep going back to it.”

Resume :

In the medical sector, we are increasingly interested in the genome and our DNA. Today several accessories like the Apple Watch for example will allow us to know our pulse. Soon we will be able to know what is missing our body, what it needs etc. The sequences of our DNA allow us to know everything that makes up our cells.

Article 1 presents the advances in the DNA sequences taken from yeast, which may allow us to find mediations to treat our diseases. We must compare what is good for our cells and what is not good. Article 2 speaks to us about how to better know our body, its needs, its lack of sugar for example. 

Advances in this technology are the source of several fiction films such as "Welcome to Gataca" which illustrates the fact that in the future we will be able to modify our genome, define our children, and even clone the most intelligent for a perfect society .