In 2007, DNA pioneer James Watson became the first person to have his entire genome sequencedmaking all of his 6 billion base pairs publicly available for research. Well, almost all of them. He left one spot blank, on the long arm of chromosome 19, where a gene called APOE lives. Certain variations in APOE increase your chances of developing Alzheimers, and Watson wanted to keep that information private.

Except it wasnt. Researchers quickly pointed out you could predict Watsons APOE variant based on signatures in the surrounding DNA. They didnt actually do it, but database managers wasted no time in redacting another two million base pairs surrounding the APOE gene.

This is the dilemma at the heart of precision medicine: It requires people to give up some of their privacy in service of the greater scientific good. To completely eliminate the risk of outing an individual based on their DNA records, youd have to strip it of the same identifying details that make it scientifically useful. But now, computer scientists and mathematicians are working toward an alternative solution. Instead of stripping genomic data, theyre encrypting it.

Gill Bejerano leads a developmental biology lab at Stanford that investigates the genetic roots of human disease. In 2013, when he realized he needed more genomic data, his lab joined Stanford Hospitals Pediatrics Departmentan arduous process that required extensive vetting and training of all his staff and equipment. This is how most institutions solve the privacy perils of data sharing. They limit who can access all the genomes in their possession to a trusted few, and only share obfuscated summary statistics more widely.

So when Bejerano found himself sitting in on a faculty talk given by Dan Boneh, head of the applied cryptography group at Stanford, he was struck with an idea. He scribbled down a mathematical formula for one of the genetic computations he uses often in his work. Afterward, he approached Boneh and showed it to him. Could you compute these outputs without knowing the inputs? he asked. Sure, said Boneh.

Last week, Bejerano and Boneh published a paper in Science that did just that. Using a cryptographic genome cloaking method, the scientists were able to do things like identify responsible mutations in groups of patients with rare diseases and compare groups of patients at two medical centers to find shared mutations associated with shared symptoms, all while keeping 97 percent of each participants unique genetic information completely hidden. They accomplished this by converting variations in each genome into a linear series of values. That allowed them to conduct any analyses they needed while only revealing genes relevant to that particular investigation.

Just like programs have bugs, people have bugs, says Bejerano. Finding disease-causing genetic traits is a lot like spotting flaws in computer code. You have to compare code that works to code that doesnt. But genetic data is much more sensitive, and people (rightly) worry that it might be used against them by insurers, or even stolen by hackers. If a patient held the cryptographic key to their data, they could get a valuable medical diagnosis while not exposing the rest of their genome to outside threats. You can make rules about not discriminating on the basis of genetics, or you can provide technology where you cant discriminate against people even if you wanted to, says Bejerano. Thats a much stronger statement.

The National Institutes of Health have been working toward such a technology since reidentification researchers first began connecting the dots in anonymous genomics data. In 2010, the agency founded a national center for Integrating Data for Analysis, Anonymization and Sharing housed on the campus of UC San Diego. And since 2015, iDash has been funding annual competitions to develop privacy-preserving genomics protocols. Another promising approach iDash has supported is something called fully homomorphic encryption, which allows users to run any computation they want on totally encrypted data without losing years of computing time.

Kristen Lauter, head of cryptography research at Microsoft, focuses on this form of encryption, and her team has taken home the iDash prize two years running. Critically, the method encodes the data in such a way that scientists dont lose the flexibility to perform medically useful genetic tests. Unlike previous encryption schemes, Lauters tool preserves the underlying mathematical structure of the data. That allows computers to do the math that delivers genetic diagnoses, for example, on totally encrypted data. Scientists get a key to decode the final results, but they never see the source.

This is extra important as more and more genetic data moves off local servers and into the cloud. The NIH lets users download human genomic data from its repositories, and in 2014, the agency started letting people store and analyze that data in private or commercial cloud environments. But under NIHs policy, its the scientists using the datanot the cloud service providerresponsible with ensuring its security. Cloud providers can get hacked, or subpoenaed by law enforcement, something researchers have no control over. That is, unless theres a viable encryption for data stored in the cloud.

If we dont think about it now, in five to 10 years a lot peoples genomic information will be used in ways they did not intend, says Lauter. But encryption is a funny technology to work with, she says. One that requires building trust between researchers and consumers. You can propose any crazy encryption you want and say its secure. Why should anyone believe you?

Thats where federal review comes in. In July, Lauters group, along with researchers from IBM and academic institutions around the world launched a process to standardize homomorphic encryption protocols. The National Institute for Standards and Technology will now begin reviewing draft standards and collecting public comments. If all goes well, genomics researchers and privacy advocates might finally have something they can agree on.

Go here to read the rest:
To Protect Genetic Privacy, Encrypt Your DNA - WIRED

Sanford Health and Harvard Medical School have collaborated to bring information and education about personal genetics and research to classrooms and communities in Massachusetts and South Dakota.

One such program the two facilities have created is the Personal Genetics Education Project (pgEd), which offers workshops that bring awareness and create community understanding about development in genetics and how they affect health.

Lindsay Kortan, who teaches ninth-grade physical science at Yankton High School (YHS), jumped at the chance to learn more about genetics by attending the pgEd Genetics and Social Justice Summer Institute in Brockton, Massachusetts this summer.

A member of the South Dakota Science Teachers Association, Kortan is also a Sanford ambassador and has done research with the organization for several years. It was through this involvement that she was invited to attend the weeklong pgEd conference.

"The setup was them showing (the attendees) their lesson plans, allowing us to experience what type of content is in the lesson and what kind of discussions/questions we might have in the classroom," she explained. "It covered a wide range of things, everything from the eugenics movement to ethics in genetics testing to personal genetics testing."

As someone who developed a strong interest in genetics through her studies at the University of South Dakota, all of this was right up Kortans alley.

"(Genetics) was one of my favorite topics to teach in a biology classroom," she said.

Prior to coming to YHS, Kortan had taught grades 10-12 science biology, physiology, physics and chemistry in the Bon Homme school district for five years.

She admitted that introducing what she learned at the conference into her current class will be difficult, but plans to spread her newfound information in other ways.

"Ive shared my knowledge with some of the other teachers and offered to help them incorporate it into their classrooms if theyre interested," she said.

She plans to be part of next summers workshop in Sioux Falls, which will be hosted by Sanford PROMISE and pgEd.

"From an education perspective, the pgED information is great for teaching our kids those critical-thinking and difficult life-decision questions they might have to encounter in their lifetime, especially now with the way genetic testing and technology is advancing," she said. "Its getting more prevalent in making decisions, even down to doctors looking at your genetic code to know what drugs they should prescribe to you, or whether the drug will be effective or not. Its important for kids to know that information before they get into those critical situations where they have to make an (important) decision. The process of going through that critical thinking and seeing different viewpoints is always a good thing in the classroom.

"Im currently pregnant, so some of those genetic questions that you get asked because of pregnancy and fertility treatments (that) I received really brought it to a personal level for me."

Follow @ReillyBiel on Twitter.

Continued here:
YHS Teacher Attends Genetics Workshop - Yankton Daily Press

Human history is often something modern man only sees as through a glass, darkly. This is particularly the case when that history did not occur in the Mediterranean, the Nile Valley, India, or China, or when there is no written record on which scholars can rely. Exacerbating the disrupting effects of time on history can be when that history occurs in a region where extensive migration has disrupted whatever temporarily stable civilization happened to have taken root at that place at any particular time.

But humans leave traces of themselves in their history and a variety of such traces have been the source of reconstructions outside conventional sources. Luigi Cavalli-Sforza began the study of human population genetics as a way to understand this history in 1971 in The Genetics of Human Populations, and later extended these studies to include language and how it influences gene flow between human populations. More recent efforts to use genetics to reconstruct history include Deep Ancestry: The Landmark DNA Quest to Decipher Our Distant Past by Spencer Wells (National Geographic: 2006), and The Seven Daughters of Eve: The Science that Reveals our Genetic Ancestry by Brian Sykes (Carrol & Graf: 2002). And even more recently, genetic studies have illuminated the "fine structure" of human populations in England (see "Fine-structure Genetic Mapping of Human Population in Britain").

Two recent reports illustrate how genetics can inform history: the first, in the American Journal of Human Genetics entitled "Continuity and Admixture in the Last Five Millennia of Levantine History from Ancient Canaanite and Present-Day Lebanese Genome Sequences"; and a second in the Proceedings of the National Academy of Sciences USA, entitled "Genomic landscape of human diversity across Madagascar." In the first study, authors* from The Wellcome Trust Sanger Institute, University of Cambridge, University of Zurich, University of Otago, Bournemouth University, Lebanese American University, and Harvard University found evidence of genetic admixture over 5,000 years of a Canaanite population that has persisted in Lebanese populations into the modern era. This population is interesting for historians in view of the central location of the ancestral home of the Canaanites, the Levant, in the Fertile Crescent that ran from Egypt through Mesopotamia. The Canaanites also inhabited the Levant during the Bronze Age and provide a critical link between the Neolithic transition from hunter gatherer societies to agriculture. This group (known to the ancient Greeks as the Phoenicians) is also a link to the great early societies recognized through their historical writings and civilizations (including the Egyptians, Assyrians, Babylonians, Persians, Greeks, and Romans); if the Canaanites had any such texts or other writings they have not survived. In addition, the type of genetic analyses that have been done for European populations has not been done for descendants of inhabitants of the Levant from this historical period. This paper uses genetic comparisons between 99 modern day residents of Lebanon (specifically, from Sidon and the Lebanese interior) and ancient DNA (aDNA) from ~3,700 year old genomes from petrous bone of individuals interred in gravesites in Sidon. For aDNA, these analyses yielded 0.4-2.3-fold genomic DNA coverage and 53-264-fold mitochondrial DNA coverage, and also compared Y chromosome sequences with present-day Lebanese, two Canaanite males and samples from the 1000 Genomes Project. Over one million single nucleotide polymorphisms (SNPs) were used for comparison.

These results indicated that the Canaanite ancestry was an admixture of local Neolithic populations and migrants from Chalcolithic (Copper Age) Iran. The authors estimate from these linkage disequilibrium studies that this admixture occurred between 6,600 and 3,550 years ago, a date that is consistent with recorded mass migrations in the region during that time. Perhaps surprisingly, their results also show that the majority of the present-day Lebanese population has inherited most of their genomic DNA from these Canaanite ancestors. These researchers also found traces of Eurasian ancestry consistent with conquests by outside populations during the period from 3,750-2,170 years ago, as well as the expansion of Phoenician maritime trade network that extended during historical time to the Iberian Peninsula.

The second paper arose from genetic studies of an Asian/African admixture population on Mozambique. This group** from the University of Toulouse, INSERM, the University of Bordeaux, University of Indonesia, the Max Plank Institute for Evolutionary Anthropology, Institut genomique, Centre Nacional de Genotypage, University of Melbourne, and the Universite de la Rochelle, showed geographic stratification between ancestral African (mostly Bantu) and Asian (Austronesean) ancestors. Cultural, historical, linguistic, ethnographic, archeological, and genetic studies supports the conclusion that Madagascar residents have traits from both populations but the effects of settlement history are termed "contentious" by these authors. Various competing putative "founder" populations (including Arabic, Indian, Papuan, and/or Jewish populations as well as first settlers found only in legend, under names like "Vazimba," "Kimosy," and "Gola") have been posited as initial settlers. These researchers report an attempt to illuminate the ancestry of the Malagasy by a study of human genetics.

These results showed common Bantu and Austronesian descent for the population with what the authors termed "limited" paternal contributions from Europe and Middle Eastern populations. The admixture of African and Austronesian populations occurred "recently" (i.e., over the past millennium) but was gender-biased and heterogeneous, which reflected for these researchers independent colonization by the two groups. The results also indicated that detectable genetic structure can be imposed on human populations over a relatively brief time (~ a few centuries).

Using a "grid-based approach" the researchers performed a high-resolution genetic diversity study that included maternal and paternal lineages as well as genome-wide data from 257 villages and over 2,700 Malagasy individuals. Maternal inheritance patterns were interrogated using mitochondrial DNA and patterns of paternity assayed using Y chromosomal sequences. Non-gender specific relationships were assessed through 2.5 million SNPs. Mitochondrial DNA analyses showed maternal inheritance from either African or East Asian origins (with one unique Madagascar variant termed M23) in roughly equal amounts, with no evidence of maternal gene flow from Europe or the Middle East. The M23 variant shows evidence of recent (within 900-1500 years) origin. Y chromosomal sequences, in contrast are much more prevalent from African origins (70.7% Africa:20.7% East Asia); the authors hypothesize that the remainder may reflect Muslim influences, with evidence of but little European ancestry.

Admixture assessments support Southeast Asian (Indonesian) and East African source populations for the Malagasy admixture. These results provide the frequency of the African component to be ~59%, the Asian component frequency to be ~37%, and the Western European component to have a frequency of about 4% (albeit with considerable variation, e.g., African ancestry can range from ~26% to almost 93%). Similar results were obtained when the frequency of chromosomal fragments shared with other populations were compared to the Malagasy population (finding the closest link to Asian populations from south Borneo, and excluding Indian, Somali, and Ethiopian populations, although the analysis was sensitive in one individual to detect French Basque ancestry). The split with ancestral Asian populations either occurred ~2,500 years ago or by slower divergence between ~2,000-3,000 years ago, while divergence with Bantu populations occurred more recently (~1,500 years ago).

There were also significant differences in geographic distribution between descendants of these ancestral populations. Maternal African lineages were found predominantly in north Madagascar, with material Asian lineages found in central and southern Madagascar (from mtDNA analyses). Paternal lineages were generally much lower overall for Asian descendants (~30% in central Madagascar) based on Y chromosome analyses. Genome-wide analyses showed "highlanders" had predominantly Asian ancestry (~65%) while coastal inhabitants had predominantly (~65%) African ancestry; these results depended greatly on the method of performing the analyses which affected the granularity of the geographic correlates. Finally, assessing admixture patterns indicated that the genetic results are consistent with single intermixing event (500-900 years ago) for all but one geographic area, which may have seen a first event 28 generations ago and a second one only 4 generations ago. These researchers also found evidence of at least one population bottleneck, where the number of individuals dropped to a few hundred people about 1,000-800 years ago.

These results are represented pictorially in the paper:

In view of the current political climate, the eloquent opening of the paper deserves attention:

Ancient long-distance voyaging between continents stimulates the imagination, raises questions about the circumstances surrounding such voyages, and reminds us that globalization is not a recent phenomenon. Moreover, populations which thereby come into contact can exchange genes, goods, ideas and technologies.

* Marc Haber, Claude Doumet-Serhal, Christiana Scheib, Yali Xue, Petr Danecek, Massimo Mezzavilla, Sonia Youhanna, Rui Martiniano, Javier Prado-Martinez, Micha Szpak, Elizabeth Matisoo-Smith, Holger Schutkowski, Richard Mikulski, Pierre Zalloua, Toomas Kivisild, Chris Tyler-Smith

** Denis Pierrona, Margit Heiskea, Harilanto Razafindrazakaa, Ignace Rakotob, Nelly Rabetokotanyb, Bodo Ravololomangab, Lucien M.-A. Rakotozafyb, Mireille Mialy Rakotomalalab, Michel Razafiarivonyb, Bako Rasoarifetrab, Miakabola Andriamampianina Raharijesyb, Lolona Razafindralambob, Ramilisoninab, Fulgence Fanonyb, Sendra Lejamblec, Olivier Thomasc, Ahmed Mohamed Abdallahc, Christophe Rocherc,, Amal Arachichec, Laure Tonasoa, Veronica Pereda-lotha, Stphanie Schiavinatoa, Nicolas Brucatoa, Francois-Xavier Ricauta, Pradiptajati Kusumaa,d,e, Herawati Sudoyod,e, Shengyu Nif, Anne Bolandg, Jean-Francois Deleuzeg, Philippe Beaujardh, Philippe Grangei, Sander Adelaarj, Mark Stonekingf, Jean-Aim Rakotoarisoab, Chantal Radimilahy, and Thierry Letelliera

Follow this link:
Using Genetics to Uncover Human History - JD Supra (press release)

Action Points

Despite the existence of evidence-based guidelines supporting genetic testing for women with a history of breast and/or ovarian cancer, most of these women didn't get tested, according to researchers.

Based on an analysis of pooled data from three cancer control modules, fewer than one in five women with a history of breast or ovarian cancer meeting National Cancer Comprehensive Network (NCCN) criteria underwent testing, reported Christopher P. Childers, MD, of the David Geffen School of Medicine at UCLA in Los Angeles, and colleagues.

Up to 10% of breast and 15% of ovarian cancers can be linked to heritable gene mutations -- most commonly mutations in the BRCA1 and BRCA2 -- which suggests that the identification of women with these mutations can direct both cancer treatment and surgical decision-making, they wrote in the Journal of Clinical Oncology.

While the rates of genetic testing in newly diagnosed patients meeting NCCN criteria have been increasing, "there is likely a large cohort of breast and ovarian cancer survivors for whom testing was not offered, pursued, or even available," Childers' group wrote.

They used nationally representative samples from the 2005, 2010, and 2015 National Health Interview Surveys (NHIS). Eligible patients included women with a history of breast cancer and/or ovarian cancer who met certain NCCN eligibility criteria based on age of diagnosis and family history:

Outcomes included the percentage of eligible individuals who either discussed genetic testing with a health professional, were advised to undergo such testing, or actually underwent testing.

Of 47,218 women identified from the three surveys, 2.7% had breast cancer. Of those women, about 36% met one or more of the eligibility criteria, and of those, 29% discussed testing with a healthcare professional, 20.2% were advised to undergo testing, and 15.3% underwent testing.

Approximately 0.4% of the women in the survey had ovarian cancer. Of those, 15.1% discussed testing, 13.1% percent were advised to undergo testing, and just 10.5% underwent testing.

Based on the pooled sample, an estimated 1,471,279 women with a history of breast and/or ovarian cancer meet one or more of the eligibility criteria. The authors determined that within this population, the rate of genetic testing was 13.8% (95% CI 10.8% to 17%).

"Using only these five criteria, this generates a population-based estimate of unmet need of genetic testing for breast and ovarian cancer survivors between 1,212,334 and 1,312,381," they noted.

Furthermore over 70% of eligible patients with breast cancer and 80% of those with ovarian cancer haven't even discussed genetic testing with a health professional.

"Given the low testing rate and large impact of identifying a heritable mutation, aggressive solutions should be considered," Childers' group suggested. "These may include universal testing for women with breast and/or ovarian cancer or other select populations, directed patient education for self-referral, or modified direct-to-consumer testing."

The study had some limitations, including the fact that NHIS collects self-reported data only, and is not validated against the medical record. Also, recall bias in terms of "advising, discussing, and testing are all possible and are likely magnied as patients become more removed from their treatment," the authors noted.

In an accompanying editorial, Kevin S. Hughes, MD, of the Avon Comprehensive Breast Evaluation Center at Massachusetts General Hospital in Boston, lamented that while many new strategies involving genetic testing have been adopted and save lives, "we have yet to apply these strategies at the population level where their effect can be generalized beyond a small number of selected patients."

Hughes wrote that while some reports of the underutilization of genetic testing have been met by calls for more genetic counselors, "there is nowhere near the number of genetic counselors needed to take on population-level testing."

The problem is that too many mutation carriers are unaware of their status and could develop cancers that could have been prevented or discovered earlier, he stated, adding that healthcare professionals need to take certain steps that will increase the rate of detection of these mutations.

He suggested some steps that can be taken, such as abbreviating pretest counseling sessions to enable more patients to be seen by genetic counselors or educated clinics. "It is time to move to population-level screening for hereditary cancer susceptibility mutations. We have thought about this for 20 years. It might be time to take action," he wrote.

Childers disclosed funded from the Agency for Healthcare Research and Quality.

Childers and co-authors disclosed no relevant relationships with industry.

Hughes disclosed relevant relationships with Hughes RiskApps, CRA Health, Myriad Genetics, Veritas Genetics, Focal Therapeutics, and Health Beacons.

2017-08-23T12:00:00-0400

Go here to read the rest:
Most Breast-Ovarian Ca Patients Miss Genetic Tests - MedPage Today

Oxford Genetics will expand its bioproduction services in the UK and target the US market through an office in Boston after receiving a 7.5m ($9.6m) investment.

The investment comes from existing investor Mercia Technologies PLC, and Invesco Perpetual and will help the bioprocessing support firm expand its global presence and increase its DNA, protein, viral and cell line service offerings.

The UK extension adds another floor in its building in Oxford which will be fitted out to increase capacity across the firms entire service offering, allowing the segregation of material flow and the isolation of individual projects, a spokesperson from Oxford Genetics told us.

This will allow us to continue to exceed regulatory requirements and provide quality assurance for our clients. We will also add more analytical, purification and process development equipment, for instance small scale bioreactors, to enable us to fully support our clients from research up to the point of GMP bioproduction.

The 6,000 sq ft extension is expected to be ready by November, and will include cell line engineering capabilities, viral vector production and purification suites, high-throughput robotic screening systems and process development facilities.

The US expansion, meanwhile, will see the firm open an office in Boston to target the large US market.

A US office is integral because it is the single largest market for our technologies and services, we were told. There has been a significant increase in the demand for our viral expression systems and cell line development for virus production.

The firm, founded in 2011, licenses its technology platforms on a non-exclusive basis to all biopharma and according to the spokesperson has had tremendous interest from firms looking for bioproduction optimisation solutions.

We have already begun to sign licenses and collaboration deals. The latter agreements are particularly interesting since they are allowing our collaborators accelerated access to some of our virus production platform technologies, which will fully mature over the next 18 months.

In the past year, Oxford Genetics has benefitted from several funding projects including a 1.6m and 1m, both from Innovate UK, to explore computational and synthetic biology approaches for optimising mammalian biomanufacturing processes, and to overcome the inefficient and costly scale-up of viral vector production, respectively.

Read the rest here:
Oxford Genetics secures investment; expands UK facility and eyes US market - BioPharma-Reporter.com