Daily Archives: October 25, 2019

Not all genes are necessary for survival these species dropped extra genetic baggage – Thehour.com

Posted: October 25, 2019 at 2:45 pm

(The Conversation is an independent and nonprofit source of news, analysis and commentary from academic experts.)

Jessica M. Velez, University of Tennessee; Alison Gerken, Kansas State University, and Amey Redkar, Universidad de Crdoba

(THE CONVERSATION) Humans, the latest tally suggests, have approximately 21,000 genes in our genome, the set of genetic information in an organism. But do we really need every gene we have? What if we lost three or four? What if we lost 3,000 or 4,000? Could we still function? Humans have variation in their genomes, but the overall size does not vary dramatically among individuals, with the exception of certain genetic disorders like Downs syndrome, which is caused by an extra copy of chromosome 21 and all the genes that it carries.

Each gene in a genome provides the code for a protein which affects our lives, from the growth of our hair to allowing us to digest certain foods. Most of the genes found in the human genome are probably safe for now, but there are some organisms which, over time, have cut down their genome to live in various habitats.

Scientists previously thought that every gene in an organisms genome was essential for survival because humans have little variation in our genome sizes from person to person. However, studies using animals with smaller, streamlined genomes have proven this untrue.

What does it take to streamline a genome? Does the organism just cut genes over time and hope for the best, or are there a series of processes that compensate for the loss of these genes? If researchers can understand how some of these small genomes work so efficiently, we can better understand how human genomes function as well. We, Amey Redkar, Alison Gerken and Jessica Velez, are a team of biologists with diverse backgrounds, all associated with the Genetics Society of America. We are interested in understanding how diverse genetic processes work in a variety of organisms and strive to communicate these exciting facts about genetics to a broad audience.

Genome structural rearrangement through evolutionary processes

Genomes can change in a variety of ways. Changes can be slight, involving just a single DNA building block, or large-scale, such as the duplication or loss of a large chunk of DNA. It is even possible to lose entire gene pathways groups of genes acting together. Large losses in DNA over time are known as genome streamlining.

Every organism is adapted to their environment, and some have achieved this through the process of genome streamlining. During this process the genome is rearranged as the species adapt to their environment. Genome streamlining enables organisms to thrive in challenging environments, such as low-nutrient ocean sites, or adapt to unique evolutionary challenges, such as those posed by flight.

Researchers explore these adaptations by studying the streamlined genomes of specific species, known as model species, to uncover what genetic material is excessive and if there is an optimum number of genes needed for an organism to survive.

Birds and plants undergo genome streamlining

A striking example of genome streamlining is seen in hummingbirds, in which the main drivers of genome size adaptations are thought to be flight and metabolic demands. These birds developed the ability to fly as well as a high-energy lifestyle, which are both reflected in their genetic code. Hummingbirds possess the smallest and least variable genome within bird species at around 900,000,000 units of DNA. The genes that encode proteins are, on average, between 27% and 50% shorter than those in mammalian genomes. These adaptations arose through the process of genome streamlining. DNA and genes which did not actively contribute to hummingbirds living at higher altitudes and having an extremely active, high-energy lifestyle were lost through adaptive mutations.

Fast-moving birds are only one of the more energetically complex species which have undergone genome streamlining. In the plant kingdom, the tiny, rootless aquatic bladderwort plant, Utricularia gibba, captures insect prey in miniature traps using vacuum suction. This plant is adapted to a predatory lifestyle through evolutionary selection of genes that allow the bladderwort to break down complex molecules using special enzymes and retain the plants structural integrity in water environments. Redundant, less important and unnecessary genes were lost.

Extreme streamlining: The smallest genome

The previous examples of reduced genome sizes raise a fundamental question: Just how streamlined can a genome be? As the genome of a species shrinks, scientists can explore how many genes a species can lose before an organism can no longer survive.

One such organism used in these studies, Prochlorococcus marinus, is a single-celled cyanobacterium living in the open ocean. At 1,800,000 units of DNA, P. marinus is known for having the smallest genome of any known photosynthetic organism.

These cyanobacteria can no longer create many essential molecules needed for survival. They have lost entire gene pathways used for the creation of amino acids, which are necessary to build proteins. As a result, P. marinus is no longer able to survive in its natural environment without the assistance of symbiotic or beneficial species which provide the amino acids P. marinus needs. In a laboratory, researchers cannot grow P. marinus without the presence of these helper species, or by directly adding the necessary amino acids P. marinus needs.

Reliance upon another species

Similar symbiotic relationships exist inside of insects. Some species of the bacterial pathogen Nardonella have undergone genome streamlining to a genome size as small as 230,000 units of DNA, shedding all genes except those necessary for DNA synthesis and the gene pathway for manufacturing tyrosine, an amino acid for building proteins.

These bacteria derive almost all of their metabolic requirements from the weevil in which they live. The bacteria, in turn, provide the final building block for the pathway in order for the weevil to generate the amino acid tyrosine that builds a darker, harder exoskeleton for the weevil which protects the insect from predators and from drying out. As a result, Nardonella both relies on and provides a benefit to the host weevil in exchange for this reliance.

Like humans, these species all have structured genetic information, but studies in these animals, plants, and bacteria have revealed that not every gene was essential to survive in their environments. As researchers continue to explore genome streamlining, we move closer to understanding how genetic adaptations arise, how the loss of genetic information affects the genomes of species, and just how few genes a species must have in order to survive in unique, challenging environments.

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This article is republished from The Conversation under a Creative Commons license. Read the original article here: http://theconversation.com/not-all-genes-are-necessary-for-survival-these-species-dropped-extra-genetic-baggage-121673.

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Digital the right medicine for healthy nation – The Australian Financial Review

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It is a huge leap forward for global medicine and especially relevant right now as we live longer, healthier lives.

According to the chief medical officer of Sydney health information company, Genome.One, Dr Leslie Burnett, genome sequencing is the holy grail of medicine. It underpins precision healthcare and for the first time it offers the potential for preventing or lessening the impacts of avoidable illnesses in an individual rather than just waiting until the condition appears and only then providing treatment.

For Australia's ageing population it is a heartening breakthrough, especially as many older Australians start to struggle with chronic diseases. Yet before precision healthcare becomes a reality, there are still a few hurdles to overcome, the major one being moving it from the laboratory into your local GP's surgery.

"The gap at present is how we connect genomics into healthcare," Genome.One chief scientific officer and founding CEO, Associate Professor Marcel Dinger says.

"At the moment there is an enormous limitation in terms of how accessible the information is and how it's actually translated into the population. The transition that needs to happen is ensuring genomic medicine has mainstream access so your local GP for example, has access to genomic information to guide their practice."

Bearing this in mind, Dinger says genomic medicine's future lies with a more connected healthcare system and "enabling digital healthcare is fundamental to genomics".

"If it remains constrained within existing clinical and laboratory processes, its promise will never come to bear," he says.

The scale of the challenge is clear for the Garvan Institute-backed start-up, which is undergoing a restructure.

Genome.One's Burnett and Dinger were speaking after a recent joint research study undertaken by Fairfax Media, publisher of The Australian Financial Review, in partnership with the Commonwealth Bank of Australia, which examined ways in which innovation can underpin the nation's economic future.

Sam Bowen, Commonwealth Bank of Australia, executive director, healthcare, institutional banking and markets, says a major focus of the survey of AFR readers was whether or not Australia's health system is fit-for-purpose considering the nation's ageing population. The research found that 71 per cent of study respondents lack confidence in Australia's preparedness.

To address these shortcomings, respondents highlighted three key initiatives.

Firstly, 49 per cent suggested the community should be encouraged to invest in, and improve, their long-term health. Secondly, more than 40 per cent of respondents recommended helping people of a working age to fund their own long-term healthcare and finally, 39 per cent of respondents indicated there needs to be more investment in technological innovations that assist with home healthcare.

Chief executive officer of aged care provider Estia Health, Norah Barlow bridles at terms like "ageing tsunami" and suggests we should stop thinking of it as a negative.

Barlow acknowledges our ageing population is a challenge and we need to work out how to ensure we have the resources and people available to deal with the coming change.

"In Australia we are not as well prepared as we should be and while there are lots of reviews going on around the aged care set-up, the big question is someone has to think about whether the aged care system is a universal system or is it a subsidised system? It's a hard political question and difficult to answer but when you're well prepared you know how you're going to fund it and what it's going to look like," she says.

Barlow believes Australians are a little ageist when it comes to looking after our elderly. She suggests our view has to change, especially as the aged care sector will generate about 20 per cent of new jobs in the future healthcare economy.

She recommends changing the structure of the aged-care model with more of a focus on rehabilitation. Rather than keeping people in residential care, they should be allowed to return home after a period of rehabilitation and hopefully access reliable and flexible home care services.

As for the future of medicine, Barlow says we have to get digital health right first and foremost. Beyond that immediate challenge, there will be much greater use of technology, with innovations like the virtual doctor, more telehealth and remote monitoring of chronic conditions.

But Barlow warns we can go too far with technology because there is a danger of losing the human interaction in medicine. "We believe that the amazing technology that is emerging will support rather than replace humans in the provision of care."

AFR readers agree. In response to a question about what technological advances are most likely to help with the ageing population, 41 per cent of respondents said that human care is most likely to help.

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Connecting gene mutations, rare genetic diseases – Baylor College of Medicine News

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Clinical exome sequencing has revolutionized genetic testing for children with inherited disorders, and Baylor College of Medicine researchers have led efforts to apply these DNA methods in the clinic. Nevertheless, in more than two-thirds of cases, the underlying genetic changes in children who undergo sequencing are unknown. Researchers everywhere are looking to new methods to analyze exome sequencing data to look for new associations between specific genes and those rare genetic diseases called Mendelian disorders. Investigators at theHuman Genome Sequencing Centerhave developed new approaches for large-scale analysis of Mendelian disorders, published today in theAmerican Journal of Human Genetics.

The investigators used an Apache Hadoop data lake, a data management platform, to aggregate the exome sequencing data from approximately 19,000 individuals from different sources. Using information from previously solved disease cases, they established methods to rapidly select candidates for Mendelian disease. They found 154 candidate disease-associating genes, which previously had no known association between mutation and rare genetic disease, according toAdam Hansen, lead author of the study and graduate student inmolecular and human geneticsat Baylor.

We found at least five people for each of these 154 genes that have very rare genetic mutations that we suspect might be causing disease, Hansen said. This shows the power of big data approaches toward accelerating the rate of discovery of associations between genes and rare diseases.

These computational methods solve the dual problems of large-scale data management and careful management of data access permission. saidDr. Richard Gibbs, study author and professor of molecular and human genetics and director of the Human Genome Sequencing Center at Baylor. They are perfect for outward display of data from the Baylor College of Medicine programs.

Exome sequencing currently only diagnoses 30 to 40% of patients, Hansen said. He hopes that diagnosis rate will increase with the discovery of new associations between mutations in certain genes and rare diseases.

The genetics community can now focus on genetic mutations in these genes when they see undiagnosed patients, Hansen said. Since our initial analysis, 19 of these genes have already been confirmed as disease-associating by independent researchers. The collective effort of the genetics community will advance our understanding of these genes and provide further evidence for their potential role in disease.

Other researchers at the Human Genome Sequencing Center who were involved in the study included Mullai Muragan, Donna Muzny, Fritz Sedlazeck, Aniko Sabo, Shalini Jhangiani, Kim Andrews, Michael Khayat, and Liwen Wang.

This work was supported in part by grants UM1 HG008898 from the National Human Genome Research Institute (NHBLI) to the Baylor College of Medicine Center for Common Disease Genetics; UM1 HG006542 from the NHGRI/National Heart, Lung, and Blood Institute (NHLBI) to the Baylor Hopkins Center for Mendelian Genomics; R01 NS058529 and R35 NS105078 (J.R.L.) from the National Institute of Neurological Disorders and Stroke (NINDS); and P50 DK096415 (N.K.) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

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Screening embryos for IQ and other complex traits is premature, study concludes – Science Magazine

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Predicting genetically complex traits from the DNA of cells taken from an IVF embryo (above) isn't easy.

By Jocelyn KaiserOct. 24, 2019 , 5:15 PM

HOUSTON, TEXASTwo years ago, news headlines began to appear about a development that made many human geneticists uneasy. A U.S. company planned to offer a test for embryos created through in vitro fertilization (IVF) that screened the entire genome for DNA variants linked to cognitive ability, in order to help couples avoid having children with intellectual impairment. Many ethicists fear such multigene analyses could one day be used to screen embryos for desirable traits as well, such as tall stature or high IQ.

For those disturbed by the prospect, a study reported here last week at the annual meeting of the American Society of Human Genetics (ASHG) may come as a relief: For now, the strategy would not work very well.

Researchers, led by statistical geneticist Shai Carmi of the Hebrew University of Jerusalem, calculated exactly how much of a boost in IQ or height could be expected by scanning for relevant DNA markers in a batch of embryos and choosing those with the highest scores. The result: The gains would be slight, and prospective parents might even end up discarding their tallest or smartest potential offspring.

The work "is the first to empirically test the viability of screening embryos" for traits that are influenced by many genes, says sociologist and demographer Melinda Mills of the University of Oxford in the United Kingdom. Such embryo screening goes beyond today's testing for single-gene disorders and currently "isn't plausible," she concludes.

Such tests are based on a polygenic risk score, a tool for evaluating a person's likelihood of a disease or trait that has emerged over the past decade from genomic studies combing through variable DNA markers in many thousands of people. Although having any one DNA variant may barely raise the risk of, say, heart disease, adding up the effects from hundreds or thousands of these markers can generate a score that helps identify people at relatively high risk of common diseases. Some direct-to-consumer DNA testing companies have begun to give customers polygenic risk scores for diseases such as heart disease, breast cancer, and diabetes.

Testing embryos, however, is hugely controversial, because of both the scientific limitations of such polygenic scores and the prospect of designer babies. Undeterred, a company called Genomic Prediction last year began to offer to test cells plucked from an IVF embryo for millions of DNA markers to produce risk scores for some common diseases and for "intellectual disability" or low IQ. Co-founder Stephen Hsu, a physicist at Michigan State University in East Lansing who has branched into genomics, says that for now, the company is not returning genetic scores predicting high IQ because "society is not ready for it."

Still, testing embryos for desirable traits could be coming soon. Most people agree it's not a good idea, but there are no data, Carmi said at the ASHG meeting. To find out whether the strategy could work, his team created virtual genomes for potential embryos by combining the DNA profiles of "parents." One parental group included actual and randomly chosen pairs of men and women from 102 Ashkenazi Jewish couples with recorded heights and the other 919 randomly paired Greek men who had cognitive test scores. The team then calculated polygenic scores for the synthetic genomes to predict height or cognitive ability. For the five embryos typically generated in an IVF cycle, the theoretical height gain from selecting an Ashkenazi couple's embryo with the highest "tallness" score was about 2.5 centimeters (with a range of 1 to 6 centimeters). Selecting for the Greek virtual embryo with the highest IQ-favorable score brought a similarly limited gain in cognitive ability, just 2.5 IQ points (in a range from one to seven points), Carmi said.

His team also looked at the actual genomes of adult offspring in 28 large families (about 10 children on average). They found that for height, unknown environmental influences, which could include factors such as diet, and genes not represented in the polygenic score apparently overpowered the assessed genetic markers: In only seven of the 28 families was the sibling with the top score for height the tallest; in five families, the best scoring child was shorter than all siblings' average height. Although Carmi's team didn't have similar real-life data for IQ, University of Edinburgh population geneticist Peter Joshi expects that any intelligence polygenic score would be even more unreliable. "You might be wrong almost as often as you're right," Joshi says. (Carmi declined to discuss his study, which is online as a preprint and in press at a journal.)

An embryo screening test that uses a polygenic score to predict low IQ is likely to face the same limitations, says Joshi, who views such testing as unethical. Hsu, however, emphasizes that Genomic Prediction doesn't use its risk scores to screen for subtle IQ distinctions, but rather to avoid embryos with rare "outlier" DNA profiles for which scores predict a high risk of an IQ below 75, indicating intellectual disability.

Carmi's embryo study comes on top of other problems with polygenic tests. Most such scores have been derived from scanning DNA of people of European ancestry, making them of limited use for other ancestry groups. And recent studies have found they often aren't as predictive for older people, men, or people living in a certain location. Scores predicting behavioral traits such as a person's level of education are even more problematic, because these traits are strongly shaped by the family environment in which a child is raised.

But such polygenic scores, for IQ as well as diseases, are sure to improve as researchers look at genetic markers in larger, more diverse groups of people. "What about when they do become predictive?" an audience member asked during an ASHG discussion, wondering whether that would justify use of the scores. "That equation can change," responded Oxford statistical geneticist Alexander Young. The ethical debate over this brave new expansion of embryo screening is just beginning.

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The really big book of plants – Cosmos

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After nine years of work, an international consortium of scientists has released gene sequences for more than 1100 plant species.

The massive undertaking described in a paper in the journal Nature is part of the One Thousand Plant Transcriptomes Initiative (1KP), a global collaboration to examine the diversification of plant species, genes and genomes back to the ancestors of flowering plants and green algae.

It reveals the timing of whole genome duplications and the origins, expansions and contractions of gene families contributing to fundamental genetic innovations enabling the evolution of algae, mosses, ferns, conifer trees, flowering plants and all other green plant lineages.

"In the tree of life, everything is interrelated, and if we want to understand how the tree of life works we need to examine the relationships between species," says lead investigator Gane Ka-Shu Wong, from the University of Alberta, Canada. That's where genetic sequencing comes in."

By sequencing and analysing genes from a broad sampling of species, the researchers say, they are better able to reconstruct gene content in the ancestors of all crops, model plant species, and gain a more complete picture of the gene and genome duplications that enabled evolutionary innovations.

More than 100 taxonomic specialists contributed material from field and living collections, including Germanys Central Collection of Algal Cultures; the Royal Botanic Gardens in London and Edinburgh; Atlanta Botanical Garden, New York Botanical Garden and Florida Museum of Natural History in the US; Fairylake Botanical Garden in Shenzhen, China; and the University of British Columbia Botanical Garden and University of Alberta in Canada.

The size and scope of the project also required the development and refinement of new computational tools for sequence assembly and phylogenetic analysis.

The timing of 244 whole genome duplications across the green plant tree of life was of particular interest to the researchers.

"Perhaps the biggest surprise of our analyses was the near absence of whole genome duplications in the algae," says Mike Barker, from University of Arizona, US.

"Building on nearly 20 years of research on plant genomes, we found that the average flowering plant genome has nearly four rounds of ancestral genome duplication dating as far back as the common ancestor of all seed plants more than 300 million years ago.

We also find multiple rounds of genome duplication in fern lineages, but there is little evidence of genome doubling in algal lineages."

In addition to genome duplications, the expansion of key gene families has contributed to the evolution of multicellularity and complexity in green plants, adds co-author Marcel Quint, from Germanys Halle University.

"Gene family expansions through duplication events catalysed diversification of plant form and function across the green tree of life," he says.

"Such expansions unleashed during terrestrialisation or even before set the stage for evolutionary innovations including the origin of the seed and later the origin of the flower."

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Sixth Circuit Ruling Bars Ohio Law Against Down Syndrome Abortions – National Review

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Two weeks ago (in Preterm Cleveland v. Himes), a divided panel of the Sixth Circuit barred the state of Ohio from enforcing its law that prohibits medical providers from performing an abortion if they have knowledge that the pregnant woman is seeking the abortion, in whole or in part, because her baby has been diagnosed as having Down syndrome.

In her majority opinion (joined by chief judge Guy Cole), Judge Bernice Bouie Donald declared that the Roe/Casey regime confers a categorical right to abortion before viability. (Donald was appointed by President Obama, Cole by President Clinton.)

In her dissent, Judge Alice Batchelder (an appointee of President George H.W. Bush) argued that the undue-burden analysis under Casey instead requires a fact-intensive inquiry that also takes into account the States interests and the benefits of the law, not just the potential burden it places on women seeking an abortion. Having failed to conduct that inquiry, the majority and the district court had no basis for enjoining the law.

Batchelder further pointed out that the Supreme Courts ruling in Gonzales v. Carhart (2007) allowed the federal ban on partial-birth abortion to apply before viability. She also invoked Justice Thomass observations (from his forceful concurring opinion last spring in Box v. Planned Parenthood) that laws like Ohios promote a States compelling interest in preventing abortion from becoming a tool of modern-day eugenics and that the Courts abortion rulings do not require states to allow eugenic abortions.

Im pleased to see that the state of Ohio has today filed a petition for rehearing en banc. The petition argues that the panel majority erred when it concluded that there is a categorical right to a pre-viability abortion: Indeed, Casey itself upheld a law prohibiting minors from getting abortions without parental consent or court approvalthat is, a law that banned those who could obtain neither consent nor court approval from getting an abortion. The petition also emphasizes the two critically important state interests that the law advances:

First, anti-eugenics laws protect the dignity of people living with conditions or traits targeted for abortion. The practice of targeting unborn children with Down syndrome for abortion devalues the lives of people living with Down syndrome.

Second, anti-eugenics laws are necessary because eugenic abortions do deep damage to the integrity of the medical profession. [Quoting Batchelder dissent.] Humans are not show dogs or racehorses. Every human life matterscertainly the people of Ohio may enact laws reflecting that viewand the medical profession [which actively promoted eugenic solutions in the early 20th century] must never again be associated with a contrary view.

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Cyberpunk 2077 Expected To Sell 20 Million Units Within One Year, Analyst Says – Wccftech

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Cyberpunk 2077 is expected to sell quite a few copies in its first year of availability, and sales may exceed the developer's previous game quite a bit.

Bloomberg analyst Matthew Kanterman predicts that Cyberpunk 2077 will sell 20 million copies within its first year of availability, which is a huge number that The Witcher 3 only managed to sell in four years.

Related Escape from Tarkov New Trailer Showcases Patch 0.12 Improvements

Earlier this week, CDPR John Mamais talked about Cyberpunk 2077 and how the game will be the last, big exceptional looking title on this current console generation.

And as the technology changes, we're expected to use it too - and we want to use it cause that stuff keeps looking cooler and cooler, all the time. We'll always keep pushing the envelope on the way a game can look, and that's one of the most exciting things about working at CD Projekt Red; getting to do just that. I think Cyberpunk is going to be a real show piece in terms of tech. Especially as this generation of consoles is fading out. I think we're going to be that one last, big, exceptional looking title on this current generation of hardware.

With the game's scope and mechanics which will make the game enjoyable for fans of role-playing games and first-person shooters,it's not hard to see how Cyberpunk 2077 will manage to sell a lot in its first year

One key point to take away is that this one singular mission was shown over fifty minutes. While aspects were duplicated, you could comfortably call it a half-hour mission, and it's one of so many that will be found within the six districts of Night City. Much like The Witcher 3, Cyberpunk 2077 is looking like it will be an undeniably huge game with so much to offer. From what I've seen over these past two years, it's one I'm absolutely looking forward to.

Cyberpunk 2077 launches on April 16th on PC, PlayStation 4 and Xbox One.

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Cyberpunk 2077 Expected To Obtain 20 Million Sales – Player.One

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Cyberpunk 2077 is still far from being released. However, the game has created a hype so big it is already expected to sell quite a few copies in its first year of launch. Even more so, CD Projekt Reds highly anticipated titles sales could exceed the studios previous game by quite a bit.

According to theBloomberg analystMatthew Kanterman, he predicts that the upcoming title will be able to sell about 20 million copies within its first year of availability. This also means that the title could surpass The Witcher 3, which only managed to sell that in four years.

Also, earlier this week, CD Projekt Reds very own John Mamais talked about Cyberpunk 2077 and how the game will be the last, big exceptional looking game on this current console generation.

As the technology changes, we're expected to use it too - and we want to use it cause that stuff keeps looking cooler and cooler, all the time. We'll always keep pushing the envelope on the way a game can look, and that's one of the most exciting things about working at CD Projekt Red; getting to do just that, he said in the interview. I think Cyberpunk is going to be a real showpiece in terms of tech. Especially as this generation of consoles is fading out. I think we're going to be that one last, big, exceptional looking title on this current generation of hardware.

The studio promises that the scope and mechanics of Cyberpunk 2077 will be very enjoyable for fans, especially for those who are fond of role-playing games and first-person shooters. And since the game is going to cater to this player base, it is not really hard to see how it will be able to sell a lot in its first year of availability.

Mamais further added that [m]uch like The Witcher 3, Cyberpunk 2077 is looking like it will be an undeniably huge game with so much to offer. From what I've seen over these past two years, it's one I'm absolutely looking forward to.

Cyberpunk 2077 launches on April 16forPC, PlayStation 4 and Xbox One.

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This Queer Cyberpunk Comic Is Action-Packed and Diverse AF – Pride.com

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Vita Ayala: I am not sure about other folks, but for me, cyberpunk is about marginalized people using the tools of oppression to change both themselves and their environment in a way that gives them (some) power. Cyberpunk is techno-noir, which, noir is another genre that I think a lot of queer folks connect with. The play with the tropes has always been very appealing, and the room for ambiguity and identity that other genres tended to shut down is something I love.

Science fiction, as a genre that is concerned often with the future, appeals to me (and I think a lot of queer folks) because of how DIFFERENT things can be there. Gender, sexuality, family dynamics, all of it is fair game in sci-fi because it is not rooted in the NOW.

Also, both cyberpunk and sci-fi have a lot of room for people of color and non-conforming expressions of self that are very much queer coded.

Danny Lore: Vita and I are in agreement about the connections between noir, cyberpunk, and marginalization. I wanted to add, as well, that for me, cyberpunk is also a path to talking about transhumanism, about our relationships to spaceand reinvention, and therefore queerness as it pertains to self-identification. Cyberpunkisthe exploration of what your body is, what your mind is, and where the two meet and where they dont.

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to Read ‘Cyberpunk 2077 – CD Projekt Red on Creating an Immersive Open World RPG – AusGamers

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We started working on the open world stuff in The Witcher 3 quite late in development, John Mamais, studio head at CD Projekt Reds Krakow studio admits. In many ways The Witcher III: Wild Hunt propelled the studio to superstar status among RPG fans. An immersive and huge open-world that pushed the cinematic possibilities of the genre forward with memorable stories, moments, and character development that fully realised the series epic fantasy ambition.

During its development, and as the size and scope of Geralts final adventure took form, the team at CD Projekt Red expanded and grew to accommodate its vision for the game. We did as much as we could, John continues. Compared to The Witcher though, Cyberpunks open world is way fucking cooler.

You've also just got the passive part of the open world, the crowd system, the conversations that are happening, the music youll hear, and the ambience, John adds, whilst moving the discussion towards Cyberpunks narrative. That was also one of the pillars during development that we would make it as immersive as possible. And that decision led us ultimately choosing first-person.

As the studios follow-up to The Witcher, every element of Cyberpunk 2077 shines with the sort of bright neon glow one can see from a great distance. But getting to this point has been a long and involved journey for the team, where even after almost an hour of stunning real-time gameplay showcased to eager fans - Cyberpunk 2077 is still not feature complete. Or, fully playable from start to finish. The goal, at least for 2019, has been to get everything in there. The Street Stories, the main story, the levels, the player choice, the secrets, the crowds, the weapons, the emergent exploration, the stunning art, the music, the immersive cinematic first-person presentation.

We're playing it all the time though, John adds. But there are blockers all over the place, because stuff is still going into the game. And that can be technically challenging for us. It's like if we can't do that now, at this point, were fucked. Now's the time to start really testing it all.

Thanks to John Mamais for his time, CD Projekt Red, and Bandai Namco. For more on Cyberpunk 2077 check our companion feature CD Projekt Red on Pushing Graphics Tech Forward and Building Night City.

This article is sponsored by ASUS.

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