Category Archives: Genetic medicine

On Saturday, Sept. 16, Baylor College of Medicine will bring a community conference and resource fair to the Midland area to provide an educational seminar and support materials for children with special needs, as well as their parents.

Provided jointly by Baylor and Texas Childrens Hospital, in collaboration with SHARE West Texas, the conference will address the role genetic evaluations play in patients with autism spectrum disorders.

Dr. Daryl Scott, associate professor of molecular and human genetics at Baylor, will walk parents through the steps of a genetic evaluation and discuss what the findings mean, citing relevant case studies. The emphasis will be placed on common causes of autism, including Fragile X syndrome, chromosomal abnormalities and mutations affecting genes linked to autism.

Conference attendees will learn how new genetic tests have made it possible to determine why some children are affected by autism spectrum disorders. When a specific case is identified, it allows physicians to provide accurate counseling and improved medical care for all family members, Scott said.

The resource fair will offer current information on care, education and research as they relate to autism spectrum disorders and encourages networking within the community by connecting patients and their families with others in similar situations.

Our goal in introducing this program to the Midland community is to broaden the awareness of these disorders while also providing parents and families with the knowledge and resources they need to cope with the behavioral and developmental disabilities that often accompany them, said Susan Fernbach, director of genetic outreach at Baylor and Texas Childrens.

The program is free and open to the public, but registration is required. The seminar will be held at Midland Shared Spaces, at 3500 North A St. To register, email Traci Hopper at thopper@sharewtx.org, or call 432-818-1259. The resource fair begins at 9 am, and the conference will follow at 10 am. Lunch will be provided.

This conference is supported by the Texas Center for Disability Studies at the University of Texas at Austin and the Texas Department of State Health Services.

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Midland to host community conference for genetic conditions - Baylor College of Medicine News (press release)

James N. Jarvis, MD, is conducting a study of the gene-environment paradigm for juvenile idiopathic arthritis pathogenesis.

Published August 14, 2017

JamesN. Jarvis, MD, clinical professor of pediatrics, will usean Arthritis Foundationgrant to study how genes and environment work together to influencethe immune dysfunction in juvenile arthritis.

After asthma, juvenile idiopathic arthritis (JIA) is the mostcommon chronic disease condition in children. While genetics play asmall role in the disease, environmental factors are also known tobe important.

Study Focuses on Influence of Epigenome

The study, titled Interplay Between Genetics andEpigenetics in Polyarticular JIA, builds upon previous workby Jarvis and his fellow researchers.

The epigenome refers to the features of DNA and the proteinsthat DNA is wrapped around that do not control the genetic makeupof a person but do influence how cells respond to the environment,says Jarvis, principal investigator on the grant.

Specifically, the epigenome determines what genes a cellwill turn on or turn off in response to environmental cues,he notes.

New Paradigm of Pathogenesis Informs Research

Like most complex traits, genetic risk for JIA is principallylocated within non-coding regions of the genome.

Our preliminary studies present the hope that we canfinally understand the gene-environment paradigm forJIA pathogenesis, Jarvis says.

Rather than regarding JIA as an autoimmunedisease, triggered by inappropriate recognition of aself protein by the adaptive immune system, Jarvishypothesizes that JIA emerges because leukocytes suffer geneticallyand epigenetically mediated perturbations that blunt their capacityto regulate and coordinate transcriptions across the genome.

This loss of coordinate regulation leads to inappropriateexpression of inflammatory mediators in the absence of the normalexternal signals typically required to initiate or sustain aninflammatory response, he says.

Our field has been dominated by a single hypothesis forJIA pathogenesis for 30 years, Jarvis notes. However,as the field of functional genomics becomes increasingly wedded tothe field of therapeutics, our work carries the promise ofcompletely new approaches to therapy based on a completelydifferent paradigm of pathogenesis.

Newly Diagnosed Children Tested in Study

The researchers are recruiting 30 children with newly diagnosedpolyarticular JIA for its study to survey the epigenome and CD4+ Tcells in them and compare the results with findings in 30 healthychildren.

We plan to build a multidimensional genomic map thatsurveys the functional epigenome, examines underlying geneticvariation and examines the effects of genetic and epigeneticvariation on gene expression, Jarvis says.

He notes the work will focus on CD4+ T cells because theresearchers have already identified interesting interactionsbetween their epigenome and transcriptome in the context oftherapeutic response in JIA.

Taking Novel Approach to Understanding Disease

Because the epigenome is the medium through which theenvironment exerts its effects on cells, Jarvis believes thatcharacterizing the epigenome in pathologically relevant cells,ascertaining where epigenetic change is linked to genetic variationand determining how genetic and epigenetic features of the genomeregulate or alter transcription is the key to truly understandingthis disease.

This project addresses a question that parents alwaysask, which I never thought wed begin to answer in mylifetime: What causes JIA? This study wontprovide the whole answer, but it will go a long way toward takingus there, he says.

The project has three specific aims:

Arthritis Patients Help Determine Funded Projects

The two-year, $730,998 grant is part of the ArthritisFoundations 2016 Delivering on Discovery awards. It was oneof only six projects out of 159 proposals chosen for funding. Forthe first time, arthritis patients helped the foundation selectprojects.

Including patient input as part of the selection processwas a new milestone in patient engagement for the ArthritisFoundation and allowed us to select projects that hold the mostpromise from an arthritis patients point of view,says Guy Eakin, senior vice president, scientific strategy.

Partners from JSMBS, Philadelphia Hospital

Collaborators from the JacobsSchool of Medicine and Biomedical Sciences are:

Other collaborators include researchers from theChildrens Hospital of Philadelphia.

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Studying How Genes, Environment Contribute to Juvenile Arthritis - UB School of Medicine and Biomedical Sciences News

After years of fanfare and a few false starts, the era of genomic medicine has finally arrived.

Across the country, thousands of patients are being treated, or having their treatment changed, based on information gleaned from their genome. Its a revolution that has been promised since the human genome was first published in 2001. But making it real required advances in information technologyinfrastructure and a precipitous drop in price.

Today, the cost of whole exome sequencing, which reveals the entire protein-coding portion of DNA, is now roughly equivalent to an MRI exam in many parts of the country, says Louanne Hudgins, M.D., president of the American College of Medical Genetics and Genomics and director of perinatal genetics at Lucile Packard Children'sHospital Stanford, Palo Alto, Calif.

Genomic sequencing is a tool like any other tool in medicine, and its a noninvasive tool that continues to provide useful information for years after it is performed, she says.

Nowhere is this genomic transformation more apparent than in the realm of cancer treatment.

Companies like Menlo Park, Calif.-based Grail Inc. are forging ahead with large-scale genomic sequencing projects in collaboration with both academic medical centers and community health systems. Grails Circulating Cell-free Genome Atlas study aims to identify genomic fingerprints shed from tumors that can be identified in a blood sample. The goal is to help identifycancers early when they are more treatable and to match a patients tumors to individualized treatment.

We are finding great enthusiasmas people want to participate in this effort, both patients and physicians, says Mark Lee, M.D., a practicing oncologist at Stanford and head of clinical development and medical affairs at Grail. Right now, he says, health systems and patients have an opportunity to participate in shaping the future of this genome-based medicine.

Supporting article:Maine Genomics Project Rethinks Cancer Care

Backed by investing giants like Amazon and Bill Gates, Grail has partnered with the Mayo Clinic, the Cleveland Clinic, the U.S. Oncology Networkand others to collect de-identified data from consenting patients for large-scale genomic studies.

And they have lots of company. The biotech company Regeneron has partnered with Pennsylvania-based Geisinger Health System to enroll interested patients in a project dubbed MyCode Community Health Initiative. A discovery-focused initiative, MyCode is also using genomic data to guide treatment decisions today. Currently, the project has enrolled more than 150,000 consenting patients and has returned what are considered actionable results to 340 patients and providersand counting.

For example, MyCode participant Barbara Barnes chose to have her reproductive organs removed after an analysis of her DNA determined that she was at increased risk for developing breast and ovarian cancer. The surgeryrevealed that she already had a fallopian tube tumor that required treatment, and the early intervention may have saved her life. She shared her story in a Facebook video produced by Geisinger.

While anecdotal success stories provide a taste of whats possible, the Geisinger-Regeneron collaboration is aimed more toward matching genotypes with treatment on a population level, and that effort is starting to yield results.

In July, the group published a report in the New England Journal of Medicine describing a variant of the gene ANGPTL3 associated with a reduced risk of cardiovascular disease detected in some MyCode participants. The gene variant codes for a protein that seems to lower cholesterol, and the company has developed a targeted treatment, evinacumab, that mimics the action of this protein. Evinacumab earned breakthrough therapy designation by the Food and Drug Administrationin April and is now in Phase 3 clinical trials for patients with an inherited tendency that manifests early in life to have high cholesterol levels, leading to deadly cardiovascular disease.

Another goal of Geisingers population-based study, says Andy Faucett, a principal investigator of MyCode and genomics researcher at Geisinger, is to determine how to scale the program and make it possible for more health systems to implement genomic screening for their patients.

We probably have a health system a week call us and ask us for help [setting up a genomics program], he says. We think its something that should be offered to every patient.

Genomic medicine has advanced to the point that genes and their variants now can be targets for drug treatments. Case in point: In May, the FDA approved pembrolizumab (Keytruda) to treat any unresectable or metastatic solid tumor with a specific genetic biomarker, irrespective of its location in the body.

This is an important first for the cancer community, Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDAs Center for Drug Evaluation and Research, said in a statement made at the time of the approval. We have now approved a drug based on a tumors biomarker without regard to the tumors original location.

Clinical trials matching genomic markers with targeted treatment are well underway and are only expected to increase, making identification of genomic targets an essential part of care.

Targeted therapies got another advance in July when an advisory panel convened by the FDA gave its unanimous recommendation for approval of the first gene-based medical treatment in the U.S. Chimeric antigen receptor T, or CAR-T,cell therapy, expected to be approved in November for a particularly aggressive form of leukemia, is the first in a wave of living drugs engineered to seek out and destroy cancerous tumors.

CAR-T cell therapy represents the culmination of decades of research to identify genetic features that are unique to each specific form of cancer that can be targeted by the immune system. The approach, coaxing a patients own immune system to recognize and attack cancerous cells, also delivers on the promise of personalized medicine, as T cells are harvested from each patient, re-engineered to recognize and attack cancer, and returned to the patient.

In the case of Novartis CTL019, the treatment on the cusp of FDA approval, complete response rates in clinical trials for acute lymphoblastic leukemia patients whohad relapsed despite multiple conventional treatments, reached 80-90%.

Physician-scientists like Brian Till of Seattles Fred Hutchinson Cancer Research Center, who has been working on CAR-T for years but was not involved in the development of CTL019, say these early results are encouraging.

We have enough data right now to be optimistic that this could become standard of care for some cancers, says Till.

He quickly added that there will likely always be a role for chemotherapy or other standard treatments and that CAR-T will probably be limited in its early days to centers that have experience managing potential toxicities. But, he added, CAR-T has the potential to be given as an outpatient treatment with careful management of side effects.

Many questions remain about whether it makes sense for healthy people to learn the secrets hidden in their DNA, but those concerns are likely to be overshadowed by a cavalcade of genomic sequencing projects and targeted therapies now hitting clinics nationwide. Simply put, genomic sequencing will be part of standard care within the next decade.

In the realm of rare-disease diagnoses and treatment, genomics already has been transformative. As recently as five years ago, patients with myriad vague symptoms, mostly infants and children, could bounce from doctor to doctor and invasive procedure to invasive procedure without ever receiving a definitive diagnosis. While some disorders still do evade diagnosis, whole genome sequencing has dramatically reduced that number.

Our ability to diagnose genetic conditions has improved dramatically, says Hudgins. And we are gaining a much better understanding of the biology behind these genetic changes. Because of these advances, therapy and management of these diseases are much improved. So the idea that there is no treatment for genetic disorders is just not true anymore.

The speed of DNA sequencing and analysis now permits near real-time diagnosis, moving it into the clinical workflow.

At Rady Childrens HospitalSan Diego, an array of Illumina sequencing machines churns through clinical samples in as few as 37 hours, according to Stephen Kingsmore, M.D., director of its Institute forGenomic Medicine.

The rapid sequence analysis has resulted in almost half of patients receiving a genomic diagnosis, while 80 percent had their care altered as a result of sequencing.

Kingsmore is consulting with a dozen other childrens hospitals that want to offer real-time genomic testing to their patients within the next year. Every hospital should have access to rapid sequencing and analysis within a few years, he says.

For prospective parents, prenatal and perinatal diagnosis has entered a new realm as well.

Cell-free DNA prenatal screening has dramatically decreased the number of invasive procedures such as amniocentesis and chorionic villus sampling that pregnant women undergo, Hudgins says. In the last few years, it has decreased fivefold in many areas of the U.S.

Even the granddaddy of all genomic medicine, gene therapy, is enjoying a renaissance. Early efforts to treat disease by replacing defective genes suffered many setbacks over the years, mainly due to the difficulty of efficiently delivering genes to affected tissues and organs. But next-generation modified viral delivery systems have shown they can get the job done safely and efficiently.

Philadelphia-based Spark Therapeutics' biologics license application for voretigene neparvovec (Luxturna)for inherited retinal disease has been accepted for review by the FDA with a decision expected early next year. The experimental treatment of 31 patients was the first successful randomized, controlled Phase 3gene therapy clinical trial, leading to FDA orphan drug designation in July.

Spark is one of several companies developing gene-based treatment for vision loss in the U.S. and Europe.

Similarly, Bluebird Bio Inc.'s gene-therapy treatment for thalassemia and sickle cell disease has shown promise. Results presented at the European Hematology Association meeting in Vienna in June suggested that a child treated for severe sickle cell disease in France might have been cured.

The company is running clinical trials to treat severe sickle cell disease at six hospitals in the U.S., including the Medical University of South Carolina. Julie Kanter, M.D., director of sickle cell research at MUSC and a primary investigator on the U.S. trial, says the new generation of gene-delivery systems is more efficient with fewer side effects.

I think weve made incredible headway and we are going to see some great things coming, she says.

Amid tumbling genomic sequencing costs, more people are having their DNA sequenced to match an underlying genetic defect withan increasing variety of targeted treatment options. From an estimated 1,000 genetic tests available only five years ago, the field has exploded to more than 52,000 available in the U.S., and that number grows daily. To find out more about what's out there, visit the National Center for Biotechnology Information's Genetic Testing Registry website at http://www.ncbi.nlm.nih.gov/gtr.

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Genomic Medicine Has Entered the Building - Hospitals & Health Networks

July 5, 2017 Credit: Cancer Research UK

Cancer patients should have routine access to genetic testing to improve diagnosis and treatment, according to England's chief medical officer.

Despite the UK being a world leader in genomic medicine its full potential is still not being realised, Professor Dame Sally Davies said in a new report.

Davies urged clinicians and the Government to work together and make wider use of new genetic techniques in an attempt to improve cancer survival rates.

Genetic testing can pinpoint the faults in DNA that have led to a cancer forming. Different cancers have different faults, and these determine which treatments may or may not work.

Such testing could lead to patients being diagnosed faster and receiving more targeted or precise treatments.

Davies said that "the age of precision medicine is now" and that the NHS must act quickly to remain world class.

"This technology has the potential to change medicine forever but we need all NHS staff, patients and the public to recognise and embrace its huge potential." said Davies.

Sir Harpal Kumar, Cancer Research UK's chief executive, agreed, saying that it would be a disservice to patients if the UK were slow to respond to innovations in this area.

The report recommends that within 5 years training should be available to current and future clinicians and that all patients should be being offered genomic tests just as readily as they're given MRI scans today.

Davies also called for research and international collaboration to be prioritised, along with investment in research and services so that patients across the country have equal access.

However the report recognises potential challenges such as data protection issues and attitudes of clinicians and the public.

"This timely report from the chief medical officer showcases just how much is now possible in genomics research and care within the NHS," added Sir Kumar.

"Cancer Research UK is determined to streamline research, to find the right clinical trial for cancer patients and to ensure laboratory discoveries benefit patients".

And the design of clinical trials are starting to change. A number of trials are underway, like Cancer Research UK's National Lung Matrix Trial with AstraZeneca and Pfizer, where patients with a certain type of lung cancer are assigned a specific treatment based on the genetic makeup of their cancer.

However, Sir Harpal Kumar stressed that to bring the report's vision to life the Government, the NHS, regulators and research funders need to act together.

Explore further: Adding abiraterone to standard treatment improves prostate cancer survival by 40 percent

Cancer Research UK is partnering with pharmaceutical companies AstraZeneca and Pfizer to create a pioneering clinical trial for patients with advanced lung cancer marking a new era of research into personalised medicines ...

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Greater access to genetic testing needed for cancer diagnosis and treatment - Medical Xpress

Driven by specialised analytics systems and software, big data analytics has decreased the time required to double medical knowledge by half, thus compressing healthcare innovation cycle period, shows the much discussed Mary Meeker study titled Internet Trends 2017.

The presentation of the study isseen as an evidence of the proverbial big data-enabled revolution, that was predicted by experts like McKinsey and Company. "A big data revolution is under way in health care. Over the last decade pharmaceutical companies have been aggregating years of research and development data into medical data bases, while payors and providers have digitised their patient records, the McKinsey report had said four years ago.

Representational image. Reuters

The Mary Meeker study shows that in the 1980s it took seven years to double medical knowledge which has been decreased to only 3.5 years after 2010, on account of massive use of big data analytics in healthcare. Though most of the samples used in the study were US based, the global trends revealed in it are well visible in India too.

"Medicine and underlying biology is now becoming a data-driven science where large amounts of structured and unstructured data relating to biological systems and human health is being generated," says Dr Rohit Gupta of MedGenome, a genomics driven research and diagnostics company based in Bengaluru.

Dr Gupta told Firstpost that big data analytics has made it possible for MedGenome, which focuses on improving global health by decoding genetic information contained in an individual genome, to dive deeper into genetics research.

While any individual's genome information is useful for detecting the known mutations for diseases, underlying new patterns of complicated diseases and their progression requires genomics data from many individuals across populations sometimes several thousands to even few millions amounting to exabytes of information, he said.

All of which would have been a cumbersome process without the latest data analytics tools that big data analytics has brought forth.

The company that started work on building India-specific baseline data to develop more accurate gene-based diagnostic testing kits in the year 2015 now conducts 400 genetic tests across all key disease areas.

What is Big Data

According to Mitali Mukerji, senior principal scientist, Council of Scientific and Industrial Research when a large number of people and institutions digitally record health data either in health apps or in digitised clinics, these information become big data about health. The data acquired from these sources can be analysed to search for patterns or trends enabling a deeper insight into the health conditions for early actionable interventions.

Big data is growing bigger But big data analytics require big data. And proliferation of Information technology in the health sector has enhanced flow of big data exponentially from various sources like dedicated wearable health gadgets like fitness trackers and hospital data base. Big data collection in the health sector has also been made possible because of the proliferation of smartphones and health apps.

The Meeker study shows that the download of health apps have increased worldwide in 2016 to nearly 1,200 million from nearly 1,150 million in the last year and 36 percent of these apps belong to the fitness and 24 percent to the diseases and treatment ones.

Health apps help the users monitor their health. From watching calorie intake to fitness training the apps have every assistance required to maintain one's health. 7 minute workout, a health app with three million users helps one get that flat tummy, lose weight and strengthen the core with 12 different exercises. Fooducate, another app, helps keep track of what one eats. This app not only counts the calories one is consuming, but also shows the user a detailed breakdown of the nutrition present in a packaged food.

For Indian users, there's Healthifyme, which comes with a comprehensive database of more than 20,000 Indian foods. It also offers an on-demand fitness trainer, yoga instructor and dietician. With this app, one can set goals to lose weight and track their food and activity. There are also companies like GOQii, which provide Indian customers with subscription-based health and fitness services on their smartphones using fitness trackers that come free.

Dr Gupta of MedGenome explains that data accumulated in wearable devices can either be sent directly to the healthcare provider for any possible intervention or even predict possible hospitalisation in the next few days.

The Meeker study shows that global shipment of wearable gadgets grew from 26 million in 2014 to 102 million in 2016.

Another area that's shown growth is electronic health records. In the US, electronic health records in office-based physicians in United States have soared from 21 percent in 2004 to 87 percent in 2015. In fact, every hospital with 500 beds (in the US) generate 50 petabytes of health data.

Back home, the Ministry of Electronics and Information Technology, Government of India, runs Aadhar-based Online Registration System, a platform to help patients book appointments in major government hospitals. The portal has the potential to emerge into a source if big data offering insights on diseases, age groups, shortcomings in hospitals and areas to improve. The website claims to have already been used to make 8,77,054 appointments till date in 118 hospitals.

On account of permeation of digital technology in health care, data growth has recorded 48% growth year on year, the Meeker study says. The accumulated mass of data, according to it, has provided deeper insights in health conditions. The study shows drastic increase of citations from 5 million in 1977 to 27 million in 2017. Easy access to big data has ensured that scientists can now direct their investigations following patterns analysed from such information and less time is required to arrive at conclusion.

If a researcher has huge sets of data at his disposal, he/she can also find out patterns and simulate it through machine learning tools, which decreases the time required to arrive at a conclusion. Machine learning methods become more robust when they are fed with results analysed from big data, says Mukerji.

She further adds, These data simulation models, rely on primary information generated from a study to build predictive models that can help assess how human body would respond to a given perturbation, says Mukerji.

The Meeker also study shows that Archimedes data simulation models can conduct clinical trials from data related to 50,000 patients collected over a period of 30 years, in just a span of two months. In absence of this model it took seven years to conduct clinical trials on data related to 2,838 patients collected over a period of seven years.

As per this report in 2016 results of 25,400 number of clinical trial was publically available against 1,900 in 2009.

The study also shows that data simulation models used by laboratories have drastically decreased time required for clinical trials. Due to emergence of big data, rise in number of publically available clinical trials have also increased, it adds.

Big data in scientific research

The developments grown around big-data in healthcare has broken the silos in scientific research. For example, the field of genomics has taken a giant stride in evolving personalised and genetic medicine with the help of big data.

A good example of how big data analytics can help modern medicine is the Human Genome Project and the innumerous researches on genetics, which paved way for personalised medicine, would have been difficult without the democratisation of data, which is another boon of big data analytics. The study shows that in the year 2008 there were only 5 personalised medicines available and it has increased to 132 in the year 2016.

In India, a Bangalore-based integrated biotech company recently launched 'Avestagenome', a project to build a complete genetic, genealogical and medical database of the Parsi community. Avestha Gengraine Technologies (Avesthagen), which launched the project believes that the results from the Parsi genome project could result in disease prediction and accelerate the development of new therapies and diagnostics both within the community as well as outside.

MedGenome has also been working on the same direction. "We collaborate with leading hospitals and research institutions to collect samples with research consent, generate sequencing data in our labs and analyse it along with clinical data to discover new mutations and disease causing perturbations in genes or functional pathways. The resultant disease models and their predictions will become more accurate as and when more data becomes available.

Mukerji says that democratisation of data fuelled by proliferation of technology and big data has also democratised scientific research across geographical boundaries. Since data has been made easily accessible, any laboratory can now proceed with research, says Mukerji.

We only need to ensure that our efforts and resources are put in the right direction, she adds.

Challenges with big data

But Dr Gupta warns that big-data in itself does not guarantee reliability for collecting quality data is a difficult task.

Moreover, he said, In medicine and clinical genomics, domain knowledge often helps and is almost essential to not only understand but also finding ways to effectively use the knowledge derived from the data and bring meaningful insights from it.

Besides, big data gathering is heavily dependent on adaptation of digital health solutions, which further restricts the data to certain age groups. As per the Meeker report, 40 percent of millennial respondents covered in the study owned a wearable. On the other hand 26 percent and 10 percent of the Generation X and baby boomers, respectively, owned wearables.

Similarly, 48 percent millennials, 38 percent Generation X and 23 percent baby boomers go online to find a physician. The report also shows that 10 percent of the people using telemedicine and wearable proved themselves super adopters of the new healthcare technology in 2016 as compared to 2 percent in 2015. Collection of big data.

Every technology brings its own challenges, with big data analytics secure storage and collection of data without violating the privacy of research subjects, is an added challenge. Something, even the Meeker study does not answer.

Digital world is really scary, says Mukerji.

Though we try to secure our data with passwords in our devices, but someone somewhere has always access to it, she says.

The health apps which are downloaded in mobile phones often become the source of big-data not only for the company that has produced it but also to the other agencies which are hunting for data in the internet. "We often click various options while browsing internet and thus knowingly or unknowingly give a third party access to some data stored in the device or in the health app, she adds.

Dimiter V Dimitrov a health expert makes similar assertions in his report, 'Medical Internet of Things and Big Data in Healthcare'. He reports that even wearables often have a server which they interact to in a different language providing it with required information.

Although many devices now have sensors to collect data, they often talk with the server in their own language, he said in his report.

Even though the industry is still at a nascent stage, and privacy remains a concern, Mukerji says that agencies possessing health data can certainly share them with laboratories without disclosing patient identity.

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Big data analytics in healthcare: Fuelled by wearables and apps, medical research takes giant leap forward - Firstpost

Precision medicine is hot and Konica Minolta wants a piece of the action. To that end, its Healthcare Americas arm is paying $1 billion to acquire Ambry Genetics.

Innovation Network Corporation of Japan (INCJ) is helping to fund the deal.Konica Minolta Healthcare Americas and INCJwill make an all-cash payment of $800 million. Ambry shareholders will get up to $200 million over the next two years.

Konica views the deal as a stepping stone marking its debut as a player in the space and plans to bring Ambrys products to Japan and then to Europe, according to a news release. Shoei Yamana, Konica Minolta CEO said in a news release that the deal marks the first in a series of initiatives to build Konicas precision medicine profile.

The future of medicine is patient-focused. Together with Ambry, we will have the most comprehensive set of diagnostic technologies for mapping an individuals genetic and biochemical makeup, as well as the capabilities to translate that knowledge into information the medical community can use to discover, prevent, and cost-effectively treat diseases, Yamana said. This will not only serve as the future foundation for our healthcare business but will pave the way for a fundamental shift in the way medicine is practiced globally.

Ambrys diagnostic offerings span multiple fields, including neurology, oncology and womens health. As with most genomics services, the business will also be generating rich data as a byproduct of its sales. Konica may be able to tap into this information in myriad ways, from drug discovery to companion diagnostics and more. Its the foundations of todays precision medicine work.

Photo: maxsattana, Getty Images

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Konica Minolta establishing itself as precision medicine player with $1B Ambry Genetics deal - MedCity News

Whenever biopharmaceutical experts and policymakers discuss medical innovation, they seem to focus only on drug discovery and development and access. While these aspects of innovation are critical to ensuring patients have safe and effective treatments, they dont provide a complete picture of the biopharmaceutical innovation model and the total investment needed to get the right medicine to the right patient at the right time. Whats missing? An understanding of the role of biopharmaceutical manufacturing and the need for a supportive policy environment in order to ensure the United States maintains its place as the leader in discovering, developing and delivering innovative medicines.

In the past decade, manufacturing has become an even more complex element of the biopharmaceutical innovation ecosystem as there have been several paradigm shifts in clinical treatments and pharmacology that make drug manufacturing significantly more challenging. First, therapeutic innovations previously developed to treat millions of patients the so-called blockbuster medicines have been replaced by the precision medicine model. This model integrates genetic information to help researchers understand which particular subgroup of patients will most likely benefit from a specific treatment. This scientific progress is leading to the development of medicines targeted for much smaller patient populations. Thus, biopharmaceutical companies now need to manufacture smaller batches and incorporate shorter production lines into their manufacturing process, which means they need to be more nimble and think beyond just efficiency to ensure production levels match the new innovative landscape in their manufacturing practices.

Second, diseases today are more often managed with medicines administered through intricate delivery systems. Complex therapies deliver important drugs directly to the site of the disease by bypassing traditional modes of delivery through oral intake. So now manufacturers have to think about how to make both the delivery device as well as the medicine.

Third, certain diseases are managed or prevented through biologics or vaccines. Unlike synthesized medicines which are made by combining specific chemical ingredients in a laboratory environment, these therapies are derived from living cell lines which cannot be fully characterized by traditional methods in a lab. For biologics and vaccines, the final product is influenced by the manufacturing process as the product is the process. An example of a therapy that requires this type of manufacturing complexity is a breakthrough vaccine for pneumococcal diseases. You may wonder what does it take to manufacture a single dose of that vaccine? It takes no less than 2.5 years, the collaboration of 1,700 researchers, engineers and other manufacturing experts, more than 400 raw materials and 678 quality tests in 581 steps to produce a single dose. Any minute deficiency in this long and laborious manufacturing process and/or ingredient integrity could possibly lead to failure.

Beyond better health, the benefit of manufacturing excellence is also captured in the economic value it generates for local communities in states all across the country. In the United States alone, there are close to 300,000 biopharmaceutical manufacturing jobs, with an average salary of close to $100,000 annually. This average salary is in the top 2 percent of all manufacturing jobs in the U.S. Pfizer currently has 17 manufacturing sites in 11 states and Puerto Rico that employ more than 12,000 people, and has invested $2 billion in these sites over the past five years. Estimates put Pfizers contribution to both direct and indirect jobs in the U.S. at 51,000.

The Pfizer facilities are not only responsible for manufacturing safe and innovative medicines, but some of the sites also produce active product ingredients. The API is the actual substance or raw material used to produce the medicine that patients consume. In fact, the Pfizer facility in Kalamazoo, Mich., is so cost-efficient that it manufactures APIs for methylprednisolone that Pfizer then sells to manufacturers in China and India, something not commonly observed in other traditional manufacturing sectors.

To make biopharmaceutical manufacturing a centerpiece of U.S. economic growth, policymakers need to address a few policy hurdles. First, they need to reform the U.S. tax code to encourage companies to further invest in U.S. pharmaceutical manufacturing. Next, the Food and Drug Administration ought to forge a proactive partnership with industry to develop practical regulatory solutions to advance and encourage domestic biopharmaceutical manufacturing expertise while protecting world-class quality control and good manufacturing processes. Lastly, the federal government needs to ensure appropriate and timely implementation of Section 3016 of the 21st Century Cures Act, which allows the FDA to issue grants to further the study of continuous manufacturing of drugs and biologics.

In an effort to get important medicines to patients in need, biopharmaceutical companies discover, develop, manage access and manufacture medicines. The innovation cycle is not complete if a company is not able to appropriately navigate the complicated yet crucial manufacturing process. A pro-active, supportive policy environment is the linchpin to ensuring the United States remains at the forefront of biopharmaceutical innovation and manufacturing.

Robert Popovian is the vice president of Pfizer U.S. Government Relations. He has two decades of experience in the biopharmaceutical health care industry and has published and presented extensively on the impact of pharmaceuticals and health care policies on health care costs and clinical outcomes.

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The Future of Manufacturing a Medicine in America - Morning Consult

BBC News

6.8m genetic medicine plan for targeted treatment BBC News Patients in Wales will benefit from stronger services and more expertise in genetic medicine, under a new strategy. The 6.8m plan has been designed to ensure Wales is able to offer treatment plans revolutionised by better understanding of human DNA. Tories ask for government assurances over genetic medicine pledgeBarry and District News all 4 news articles »

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6.8m genetic medicine plan for targeted treatment - BBC News

Like many of you I find myself watching with a breaking heart as a young British couple faces the likely prospects that their young child, Charlie Gard, is going to die.

Charlie has mitochondrial DNA depletion syndrome which causes muscle weakness as well as the loss of functions including eating, talking, breathing and walking. He remains on life support as he has for the last eight months as medical professionals sought to care for the rare genetic condition.

Time is apparently up as far as the European health care and court system is concerned. The Great Ormond Street Hospital where little Charlie has been cared for recently received permission to turn off the life support, against the parent's wishes, as the child's condition continues to worsen. And people wonder what's wrong with socialized medicine. When fighting for a life becomes a dollars and cents decision, the individual's ability to battle is weighed against the government's purse. I guess the one thing you will find out with socialized medicine is exactly how much you're worth down to the last penny, at least in the government's eyes,

But what puzzles me is why there is such resistance against the child receiving medical care offered in America. Apparently the U.S. has one of two hospitals which have stepped up and offered to use an experimental treatment on young Charlie which they feel might offer him a slight chance of survival. Although the chance is slight, the parents Chris Gard and Connie Yates, are desperate to try anything at this point to give Charlie a fighting change.

Pope Francis and President Trump are both offering support of prayers and care for the young man as opposed to just writing him off. If there's a chance, even the slightest, for this child to survive and for those parents not to have to bury their son, then it should be explored.

So the question remains, if Charlie can be safely transported and there are entities interested in making it happen, why is the English medical community so opposed. Is it stubbornness? Is it a statement that impacts their system? Is it ego? Or is it just the culture of death we live in today sees so little value in human life that it's just not worth the time, effort and monetary investment? Is there a price tag on a life? And if so what determines that price tag?

Charlie deserves every opportunity to live. To fight. To receive care. His parents have the right to try and save their son.

If you disagree, I guess you just need ask yourself, if Christ was standing before you and you had to explain your feelings about the fate of this child, how would he feel about the justification behind your feelings?

Until the young boy passes I will continue to pray for his life and healing and every bit as important, that his life be regarded as something worth fighting for until the last resource is exhausted. But ultimately, it's in God's hands.

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Perplexed by English medical professionals desire to prevent care - Spencer Daily Reporter

Deoxyribonucleic acid (i;[1]DNA) is a molecule that carries the genetic instructions used in the growth, development, functioning and reproduction of all known living organisms and many viruses. DNA and RNA are nucleic acids; alongside proteins, lipids and complex carbohydrates (polysaccharides), they are one of the four major types of macromolecules that are essential for all known forms of life. Most DNA molecules consist of two biopolymer strands coiled around each other to form a double helix.

The two DNA strands are termed polynucleotides since they are composed of simpler monomer units called nucleotides.[2][3] Each nucleotide is composed of one of four nitrogen-containing nucleobaseseither cytosine (C), guanine (G), adenine (A), or thymine (T)and a sugar called deoxyribose and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together (according to base pairing rules (A with T, and C with G) with hydrogen bonds to make double-stranded DNA. The total amount of related DNA base pairs on Earth is estimated at 5.0 x 1037, and weighs 50 billion tonnes.[4] In comparison, the total mass of the biosphere has been estimated to be as much as 4 trillion tons of carbon (TtC).[5]

DNA stores biological information. The DNA backbone is resistant to cleavage, and both strands of the double-stranded structure store the same biological information. This information is replicated as and when the two strands separate. A large part of DNA (more than 98% for humans) is non-coding, meaning that these sections do not serve as patterns for protein sequences.

The two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes biological information. RNA strands are created using DNA strands as a template in a process called transcription. Under the genetic code, these RNA strands are translated to specify the sequence of amino acids within proteins in a process called translation.

Within eukaryotic cells, DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts.[6] In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the eukaryotic chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

DNA was first isolated by Friedrich Miescher in 1869. Its molecular structure was identified by James Watson and Francis Crick in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity. The unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials.[7]

DNA is a long polymer made from repeating units called nucleotides.[8][9] The structure of DNA is non-static,[10] all species comprises two helical chains each coiled round the same axis, and each with a pitch of 34ngstrms (3.4nanometres) and a radius of 10ngstrms (1.0nanometre).[11] According to another study, when measured in a particular solution, the DNA chain measured 22 to 26ngstrms wide (2.2 to 2.6nanometres), and one nucleotide unit measured 3.3 (0.33nm) long.[12] Although each individual repeating unit is very small, DNA polymers can be very large molecules containing millions of nucleotides. For instance, the DNA in the largest human chromosome, chromosome number 1, consists of approximately 220 million base pairs[13] and would be 85mm long if straightened.

In living organisms DNA does not usually exist as a single molecule, but instead as a pair of molecules that are held tightly together.[14][15] These two long strands entwine like vines, in the shape of a double helix. The nucleotide contains both a segment of the backbone of the molecule (which holds the chain together) and a nucleobase (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a nucleoside and a base linked to a sugar and one or more phosphate groups is called a nucleotide. A polymer comprising multiple linked nucleotides (as in DNA) is called a polynucleotide.[16]

The backbone of the DNA strand is made from alternating phosphate and sugar residues.[17] The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These asymmetric bonds mean a strand of DNA has a direction. In a double helix, the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are said to have a directionality of five prime (5) and three prime (3), with the 5 end having a terminal phosphate group and the 3 end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the alternative pentose sugar ribose in RNA.[15]

The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases.[19] In the aqueous environment of the cell, the conjugated bonds of nucleotide bases align perpendicular to the axis of the DNA molecule, minimizing their interaction with the solvation shell. The four bases found in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs with thymine and guanine pairs with cytosine. It was represented by A-T base pairs and G-C base pairs.[20][21]

The nucleobases are classified into two types: the purines, A and G, being fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T.[15] A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology.[22]

Uracil is not usually found in DNA, occurring only as a breakdown product of cytosine. However, in several bacteriophages, Bacillus subtilis bacteriophages PBS1 and PBS2 and Yersinia bacteriophage piR1-37, thymine has been replaced by uracil.[23] Another phage - Staphylococcal phage S6 - has been identified with a genome where thymine has been replaced by uracil.[24]

Base J (beta-d-glucopyranosyloxymethyluracil), a modified form of uracil, is also found in several organisms: the flagellates Diplonema and Euglena, and all the kinetoplastid genera.[25] Biosynthesis of J occurs in two steps: in the first step a specific thymidine in DNA is converted into hydroxymethyldeoxyuridine; in the second HOMedU is glycosylated to form J.[26] Proteins that bind specifically to this base have been identified.[27][28][29] These proteins appear to be distant relatives of the Tet1 oncogene that is involved in the pathogenesis of acute myeloid leukemia.[30] J appears to act as a termination signal for RNA polymerase II.[31][32]

Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. One groove, the major groove, is 22 wide and the other, the minor groove, is 12 wide.[33] The width of the major groove means that the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as transcription factors that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove.[34] This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form.

In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix is called a base pair. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can thus be pulled apart like a zipper, either by a mechanical force or high temperature.[35] As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.[9]

The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, right). DNA with high GC-content is more stable than DNA with low GC-content.

As noted above, most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double stranded structure (dsDNA) is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart a process known as melting to form two single-stranded DNA molecules (ssDNA) molecules. Melting occurs at high temperature, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).

The stability of the dsDNA form depends not only on the GC-content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the "melting temperature", which is the temperature at which 50% of the ds molecules are converted to ss molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high GC-content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands.[36] In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart.[37]

In the laboratory, the strength of this interaction can be measured by finding the temperature necessary to break the hydrogen bonds, their melting temperature (also called Tm value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules (ssDNA) have no single common shape, but some conformations are more stable than others.[38]

A DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein.[39] The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear.[40] One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.[41]

A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes.[42] In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription,[43] while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.[44]

DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound.[45] If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases.[46] These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.[47]

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms.[17] The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, and the presence of polyamines in solution.[48]

The first published reports of A-DNA X-ray diffraction patternsand also B-DNAused analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA.[49][50] An alternative analysis was then proposed by Wilkins et al., in 1953, for the in vivo B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions.[51] In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double-helix.[11]

Although the B-DNA form is most common under the conditions found in cells,[52] it is not a well-defined conformation but a family of related DNA conformations[53] that occur at the high hydration levels present in living cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.[54][55]

Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes.[56][57] Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form.[58] These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.[59]

For many years exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA. A report in 2010 of the possibility in the bacterium GFAJ-1, was announced,[60][60][61] though the research was disputed,[61][62] and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.[63]

At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3 ends of chromosomes.[64] These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected.[65] In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.[66]

These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure.[68] These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit.[69] Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.

In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins.[70] At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.[68]

In DNA, fraying occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible.[71] Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.

The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see Chromatin remodeling). There is, further, crosstalk between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression.[72]

For one example, cytosine methylation, produces 5-methylcytosine, which is important for X-inactivation of chromosomes.[73] The average level of methylation varies between organisms the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine.[74] Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations.[75] Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain,[76] and the glycosylation of uracil to produce the "J-base" in kinetoplastids.[77][78]

DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases.[80] On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks.[81] A typical human cell contains about 150,000 bases that have suffered oxidative damage.[82] Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions, deletions from the DNA sequence, and chromosomal translocations.[83] These mutations can cause cancer. Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer.[84][85] DNA damages that are naturally occurring, due to normal cellular processes that produce reactive oxygen species, the hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging.[86][87][88]

Many mutagens fit into the space between two adjacent base pairs, this is called intercalation. Most intercalators are aromatic and planar molecules; examples include ethidium bromide, acridines, daunomycin, and doxorubicin. For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations.[89] As a result, DNA intercalators may be carcinogens, and in the case of thalidomide, a teratogen.[90] Others such as benzo[a]pyrene diol epoxide and aflatoxin form DNA adducts that induce errors in replication.[91] Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells.[92]

DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes.[93] The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation, which depends on the same interaction between RNA nucleotides. In alternative fashion, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here the focus is on the interactions between DNA and other molecules that mediate the function of the genome.

Genomic DNA is tightly and orderly packed in the process called DNA condensation, to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus, with small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid.[94] The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, and regulatory sequences such as promoters and enhancers, which control transcription of the open reading frame.

In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences.[95] The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value, among species represent a long-standing puzzle known as the "C-value enigma".[96] However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.[97]

Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes, but are important for the function and stability of chromosomes.[65][99] An abundant form of noncoding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation.[100] These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.[101]

A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).

In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (43combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA, and TAG codons.

Cell division is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called DNA polymerase. This enzyme makes the complementary strand by finding the correct base through complementary base pairing, and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5 to 3 direction, different mechanisms are used to copy the antiparallel strands of the double helix.[102] In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.

Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 g/L, and its concentration in natural aquatic environments may be as high at 88 g/L.[103] Various possible functions have been proposed for eDNA: it may be involved in horizontal gene transfer;[104] it may provide nutrients;[105] and it may act as a buffer to recruit or titrate ions or antibiotics.[106] Extracellular DNA acts as a functional extracellular matrix component in the biofilms of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm;[107] it may contribute to biofilm formation;[108] and it may contribute to the biofilm's physical strength and resistance to biological stress.[109]

All the functions of DNA depend on interactions with proteins. These protein interactions can be non-specific, or the protein can bind specifically to a single DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved.[110][111] The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones, making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are thus largely independent of the base sequence.[112] Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation.[113] These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription.[114] Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA.[115] These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.[116]

A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair.[117] These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.

In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription.[119] Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase.[120]

As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes.[121] Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.[34]

Nucleases are enzymes that cut DNA strands by catalyzing the hydrolysis of the phosphodiester bonds. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called exonucleases, while endonucleases cut within strands. The most frequently used nucleases in molecular biology are the restriction endonucleases, which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5-GATATC-3 and makes a cut at the horizontal line. In nature, these enzymes protect bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system.[123] In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting.

Enzymes called DNA ligases can rejoin cut or broken DNA strands.[124] Ligases are particularly important in lagging strand DNA replication, as they join together the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.[124]

Topoisomerases are enzymes with both nuclease and ligase activity. These proteins change the amount of supercoiling in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break.[46] Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix.[125] Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.[47]

Helicases are proteins that are a type of molecular motor. They use the chemical energy in nucleoside triphosphates, predominantly adenosine triphosphate (ATP), to break hydrogen bonds between bases and unwind the DNA double helix into single strands.[126] These enzymes are essential for most processes where enzymes need to access the DNA bases.

Polymerases are enzymes that synthesize polynucleotide chains from nucleoside triphosphates. The sequence of their products are created based on existing polynucleotide chainswhich are called templates. These enzymes function by repeatedly adding a nucleotide to the 3 hydroxyl group at the end of the growing polynucleotide chain. As a consequence, all polymerases work in a 5 to 3 direction.[127] In the active site of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use.

In DNA replication, DNA-dependent DNA polymerases make copies of DNA polynucleotide chains. To preserve biological information, it is essential that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a proofreading activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3 to 5 exonuclease activity is activated and the incorrect base removed.[128] In most organisms, DNA polymerases function in a large complex called the replisome that contains multiple accessory subunits, such as the DNA clamp or helicases.[129]

RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include reverse transcriptase, which is a viral enzyme involved in the infection of cells by retroviruses, and telomerase, which is required for the replication of telomeres.[64][130] Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure.[65]

Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.[131]

A DNA helix usually does not interact with other segments of DNA, and in human cells the different chromosomes even occupy separate areas in the nucleus called "chromosome territories".[133] This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is in chromosomal crossover which occurs during sexual reproduction, when genetic recombination occurs. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.

Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of natural selection and can be important in the rapid evolution of new proteins.[134] Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.[135]

The most common form of chromosomal crossover is homologous recombination, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocations and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as RAD51.[136] The first step in recombination is a double-stranded break caused by either an endonuclease or damage to the DNA.[137] A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one Holliday junction, in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA.[138]

DNA contains the genetic information that allows all modern living things to function, grow and reproduce. However, it is unclear how long in the 4-billion-year history of life DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material.[139][140] RNA may have acted as the central part of early cell metabolism as it can both transmit genetic information and carry out catalysis as part of ribozymes.[141] This ancient RNA world where nucleic acid would have been used for both catalysis and genetics may have influenced the evolution of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication accuracy and a large number of bases increasing the catalytic efficiency of ribozymes.[142] However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible because DNA survives in the environment for less than one million years, and slowly degrades into short fragments in solution.[143] Claims for older DNA have been made, most notably a report of the isolation of a viable bacterium from a salt crystal 250 million years old,[144] but these claims are controversial.[145][146]

Building blocks of DNA (adenine, guanine and related organic molecules) may have been formed extraterrestrially in outer space.[147][148][149] Complex DNA and RNA organic compounds of life, including uracil, cytosine, and thymine, have also been formed in the laboratory under conditions mimicking those found in outer space, using starting chemicals, such as pyrimidine, found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), the most carbon-rich chemical found in the universe, may have been formed in red giants or in interstellar cosmic dust and gas clouds.[150]

Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction, and to manipulate it in the laboratory, such as restriction digests and the polymerase chain reaction. Modern biology and biochemistry make intensive use of these techniques in recombinant DNA technology. Recombinant DNA is a man-made DNA sequence that has been assembled from other DNA sequences. They can be transformed into organisms in the form of plasmids or in the appropriate format, by using a viral vector.[151] The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research,[152] or be grown in agriculture.[153][154]

Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator. This process is formally termed DNA profiling, but may also be called "genetic fingerprinting". In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA.[155] However, identification can be complicated if the scene is contaminated with DNA from several people.[156] DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys,[157] and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.[158]

The development of forensic science, and the ability to now obtain genetic matching on minute samples of blood, skin, saliva, or hair has led to re-examining many cases. Evidence can now be uncovered that was scientifically impossible at the time of the original examination. Combined with the removal of the double jeopardy law in some places, this can allow cases to be reopened where prior trials have failed to produce sufficient evidence to convince a jury. People charged with serious crimes may be required to provide a sample of DNA for matching purposes. The most obvious defence to DNA matches obtained forensically is to claim that cross-contamination of evidence has occurred. This has resulted in meticulous strict handling procedures with new cases of serious crime. DNA profiling is also used successfully to positively identify victims of mass casualty incidents,[159] bodies or body parts in serious accidents, and individual victims in mass war graves, via matching to family members.

DNA profiling is also used in DNA paternity testing to determine if someone is the biological parent or grandparent of a child with the probability of parentage is typically 99.99% when the alleged parent is biologically related to the child. Normal DNA sequencing methods happen after birth but there are new methods to test paternity while a mother is still pregnant.[160]

Deoxyribozymes, also called DNAzymes or catalytic DNA are first discovered in 1994.[161] They are mostly single stranded DNA sequences isolated from a large pool of random DNA sequences through a combinatorial approach called in vitro selection or systematic evolution of ligands by exponential enrichment (SELEX). DNAzymes catalyze variety of chemical reactions including RNA-DNA cleavage, RNA-DNA ligation, amino acids phosphorylation-dephosphorylation, carbon-carbon bond formation, and etc. DNAzymes can enhance catalytic rate of chemical reactions up to 100,000,000,000-fold over the uncatalyzed reaction.[162] The most extensively studied class of DNAzymes are RNA-cleaving types which have been used to detect different metal ions and designing therapeutic agents. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead-specific),[161] the CA1-3 DNAzymes (copper-specific),[163] the 39E DNAzyme (uranyl-specific) and the NaA43 DNAzyme (sodium-specific).[164] The NaA43 DNAzyme, which is reported to be more than 10,000-fold selective for sodium over other metal ions, was used to make a real-time sodium sensor in living cells.

Bioinformatics involves the development of techniques to store, data mine, search and manipulate biological data, including DNA nucleic acid sequence data. These have led to widely applied advances in computer science, especially string searching algorithms, machine learning and database theory.[165] String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides.[166] The DNA sequence may be aligned with other DNA sequences to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment, are used in studying phylogenetic relationships and protein function.[167] Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without the annotations that identify the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products and their possible functions in an organism even before they have been isolated experimentally.[168] Entire genomes may also be compared, which can shed light on the evolutionary history of particular organism and permit the examination of complex evolutionary events.

DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties.[169] DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based and using the DNA origami method) and three-dimensional structures in the shapes of polyhedra.[170]Nanomechanical devices and algorithmic self-assembly have also been demonstrated,[171] and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.[172]

Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their phylogeny.[173] This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population geneticists can learn the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology; For example, DNA evidence is being used to try to identify the Ten Lost Tribes of Israel.[174][175]

In a paper published in Nature in January 2013, scientists from the European Bioinformatics Institute and Agilent Technologies proposed a mechanism to use DNA's ability to code information as a means of digital data storage. The group was able to encode 739 kilobytes of data into DNA code, synthesize the actual DNA, then sequence the DNA and decode the information back to its original form, with a reported 100% accuracy. The encoded information consisted of text files and audio files. A prior experiment was published in August 2012. It was conducted by researchers at Harvard University, where the text of a 54,000-word book was encoded in DNA.[176][177]

DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein".[178][179] In 1878, Albrecht Kossel isolated the non-protein component of "nuclein", nucleic acid, and later isolated its five primary nucleobases.[180][181] In 1919, Phoebus Levene identified the base, sugar and phosphate nucleotide unit.[182] Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. Levene thought the chain was short and the bases repeated in a fixed order. In 1937, William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.[183]

In 1927, Nikolai Koltsov proposed that inherited traits would be inherited via a "giant hereditary molecule" made up of "two mirror strands that would replicate in a semi-conservative fashion using each strand as a template".[184][185] In 1928, Frederick Griffith in his experiment discovered that traits of the "smooth" form of Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form.[186][187] This system provided the first clear suggestion that DNA carries genetic informationthe AveryMacLeodMcCarty experimentwhen Oswald Avery, along with coworkers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle in 1943.[188] DNA's role in heredity was confirmed in 1952, when Alfred Hershey and Martha Chase in the HersheyChase experiment showed that DNA is the genetic material of the T2 phage.[189]

In 1953, James Watson and Francis Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature.[11] Their double-helix, molecular model of DNA was then based on one X-ray diffraction image (labeled as "Photo 51")[190] taken by Rosalind Franklin and Raymond Gosling in May 1952, and the information that the DNA bases are paired.

Experimental evidence supporting the Watson and Crick model was published in a series of five articles in the same issue of Nature.[191] Of these, Franklin and Gosling's paper was the first publication of their own X-ray diffraction data and original analysis method that partly supported the Watson and Crick model;[50][192] this issue also contained an article on DNA structure by Maurice Wilkins and two of his colleagues, whose analysis and in vivo B-DNA X-ray patterns also supported the presence in vivo of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the prior two pages of Nature.[51] In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine.[193] Nobel Prizes are awarded only to living recipients. A debate continues about who should receive credit for the discovery.[194]

In an influential presentation in 1957, Crick laid out the central dogma of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis".[195] Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the MeselsonStahl experiment.[196] Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg to decipher the genetic code.[197] These findings represent the birth of molecular biology.

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