Category Archives: Transhuman News

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

See the article here:
Using Genetics to Uncover Human History - JD Supra (press release)

Deadly gene mutations removed from human embryos in landmark study, reports The Guardian. Researchers have used a gene-editing technique to repair faults in DNA that can cause an often-fatal heart condition called hypertrophic cardiomyopathy.

This inherited heart condition is caused by a genetic change (mutation) in one or more genes. Babies born with hypertrophic cardiomyopathy have diseased and stiff heart muscles, which can lead to sudden unexpected death in childhood and in young athletes.

In this latest study researchers used a technique called CRISPR-cas9 to target and then remove faulty genes. CRISPR-cas9 acts like a pair of molecular scissors, allowing scientists to cut out certain sections of DNA. The technique has attracted a great deal of excitement in the scientific community since it was released in 2014. But as yet, there have been no practical applications for human health.

The research is at an early stage and cannot legally be used as treatment to help families affected by hypertrophic cardiomyopathy. And none of the modified embryos were implanted in the womb.

While the technique showed a high degree of accuracy, its unclear whether it is safe enough to be developed as a treatment. The sperm used in the study came from just one man with faulty genes, so the study needs to be repeated using cells from other people, to be sure that the findings can be replicated.

Scientists say it is now important for society to start a discussion about the ethical and legal implications of the technology. It is currently against the law to implant genetically altered human embryos to create a pregnancy, although such embryos can be developed for research.

The study was carried out by researchers from Oregon Health and Science University and the Salk Institute for Biological Studies in the US, the Institute for Basic Science and Seoul University in Korea, and BGI-Shenzen and BGI-Quingdao in China. It was funded by Oregon Health and Science University, the Institute for Basic Science, the G. Harold and Leila Y. Mathers Charitable Foundation, the Moxie Foundation and the Leona M. and HarryB. Helmsley Charitable Trust and the Shenzhen Municipal Government of China. The study was published in the peer-reviewed journal Nature.

The Guardian carried a clear and accurate report of the study. While their reports were mostly accurate, ITV News, Sky News and The Independent over-stated the current stage of research, with Sky News and ITV News saying it could eradicate thousands of inherited conditions and the Independent claiming it opens the possibility for inherited diseases to be wiped out entirely. While this may be possible, we dont know whether other inherited diseases might be as easily targeted as this gene mutation.

Finally, the Daily Mail rolls out the arguably tired clich of the technique leading to designer babies, which seems irrelevant at this point. The CRISPR-cas9 technique is only in its infancy and (ethics aside) its simply not possible to use genetic editing to select desirable characteristics - most of which are not the result of one single, identifiable gene. No reputable scientist would attempt such a procedure.

This was a series of experiments carried out in laboratories, to test the effects of the CRISPR-Cas9 technique on human cells and embryos. This type of scientific research helps us understand more about genes and how they can be changed by technology. It doesnt tell us what the effects would be if this was used as a treatment.

Researchers carried out a series of experiments on human cells, using the CRISPR-cas9 technique first on modified skin cells, then on very early embryos, and then on eggs at the point of fertilisation by sperm. They used genetic sequencing and analysis to assess the effects of these different experiments on cells and how they developed, up to five days. They looked specifically to see what proportion of cells carrying faulty mutations could be repaired, whether the process caused other unwanted mutations, and whether the process repaired all cells in an embryo, or just some of them.

They used skin cells (which were modified into stem cells) and sperm from one man, who carried the MYBPC3 mutation in his genome, and donor eggs from women without the genetic mutation. This is the mutation known to cause hypertrophic cardiomyopathy.

Normally in such cases, roughly half the embryos would have the mutation and half would not, as theres a 50-50 chance of the embryo inheriting the male or female version of the gene.

The CRISPR-cas9 technique can be used to select and delete specific genes from a strand of DNA. When this happens, usually the cut ends of the strand join together, but this causes problems so cant be used in the treatment of humans. The scientists created a genetic template of the healthy version of the gene, which they introduced at the same time as using CRISPR-cas9 to cut the mutated gene. They hoped the DNA would repair itself with a healthy version of the gene.

One important problem with changing genetic material is the development of mosaic embryos, where some of the cells have corrected genetic material and others have the original faulty gene. If that happened, doctors would not be able to tell whether or not an embryo was healthy.

The scientists needed to test all the cells in the embryos produced in the experiment, to see whether all cells had the corrected gene or whether the technique had resulted in a mixture. They also did whole genome sequencing on some embryos, to test for unrelated genetic changes that might have been introduced accidentally during the process.

All embryos in the study were destroyed, in line with legislation about genetic research on embryos.

Researchers found that the technique worked on some of the stem cells and embryos, but worked best when used at the point of fertilisation of the egg. There were important differences between the way the repair worked on the stem cells and the egg.

Only 28% of the stem cells were affected by the CRISPR-cas9 technique. Of these, most repaired themselves by joining the ends together, and only 41% were repaired by using a corrected version of the gene.

67% of the embryos exposed to CRISPR-cas9 had only the correct version of the gene higher than the 50% that would have been expected had the technique not been used. 33% of embryos had the mutated version of the gene, either in some or all their cells.

Importantly, the embryos didnt seem to use the template injected into the zygote to carry out the repair, in the way the stem cells did. They used the female version of the healthy gene to carry out the repair, instead.

Of the embryos created using CRISPR-cas9 at the point of fertilisation, 72% had the correct version of the gene in all their cells, and 28% had the mutated version of the gene in all their cells. No embryos were mosaic a mixture of cells with different genomes.

The researchers found no evidence of mutations induced by the technique, when they examined the cells using a variety of techniques. However, they did find some evidence of gene deletions caused by DNA strands splicing (joining) themselves together without repairing the faulty gene.

The researchers say they have demonstrated how human embryos employ a different DNA damage repair system to adult stem cells, which can be used to repair breaks in DNA made using the CRISPR-cas9 gene-editing technique.

They say that targeted gene correction could potentially rescue a substantial portion of mutant human embryos, and increase the numbers available for transfer for couples using pre-implantation diagnosis during IVF treatment.

However, they caution that despite remarkable targeting efficiency, CRISPR-cas9-treated embryos would not currently be suitable for transfer. Genome editing approaches must be further optimised before clinical application can be considered, they say.

Currently, genetically-inherited conditions like hypertrophic cardiomyopathy cannot be cured, only managed to reduce the risk of sudden cardiac death. For couples where one partner carries the mutated gene, the only option to avoid passing it on to their children is pre-implantation genetic diagnosis. This involves using IVF to create embryos, then testing a cell of the embryo to see whether it carries the healthy or mutated version of the gene. Embryos with healthy versions of the gene are then selected for implantation in the womb.

Problems arise if too few or none of the embryos have the correct version of the gene. The researchers suggest their technique could be used to increase the numbers of suitable embryos. However, the research is still at an early stage and has not yet been shown to be safe or effective enough to be considered as a treatment.

The other major factor is ethics and the law. Some people worry that gene editing could lead to designer babies, where couples use the tool to select attributes like hair colour, or even intelligence. At present, gene editing could not do this. Most of our characteristics, especially something as complex as intelligence, are not the result of one single, identifiable gene, so could not be selected in this way. And its likely that, even if gene editing treatments became legally available, they would be restricted to medical conditions.

Designer babies aside, society needs to consider what is acceptable in terms of editing human genetic material in embryos. Some people think that this type of technique is "playing God" or is ethically unacceptable because it involves discarding embryos that carry faulty genes. Others think that its rational to use the scientific techniques we have developed to eliminate causes of suffering, such as inherited diseases.

This research shows that the questions of how we want to legislate for this type of technique are becoming pressing. While the technology is not there yet, it is advancing fast. This research shows just how close we are getting to making genetic editing of human embryos a reality.

Read the original post:
Gene editing used to repair diseased genes in embryos - NHS Choices

JTA Parents of children born with Tay-Sachs disease talk about three deaths.

There is the moment when parents first learn that their child has been diagnosed with the fatal disease. Then there is the moment when the childs condition has deteriorated so badly blind, paralyzed, non-responsive that he or she has to be hospitalized. Then theres the moment, usually by age 5, when the child finally dies.

There used to be an entire hospital unit 16 or 17 beds at Kingsbook Jewish Medical Center in Brooklyn devoted to taking care of these children. It was often full, with a waiting list that admitted new patients only when someone elses child had died.

But by the late 1990s that unit was totally empty, and it eventually shut down. Its closure was a visible symbol of one of the most dramatic Jewish success stories of the past 50 years: the near-eradication of a deadly genetic disease.

Since the 70s, the incidence of Tay-Sachs has fallen by more than 90 percent among Jews, thanks to a combination of scientific advances and volunteer community activism that brought screening for the disease into synagogues, Jewish community centers and, eventually, routine medical care.

Until 1969, when doctors discovered the enzyme that made testing possible to determine whether parents were carriers of Tay-Sachs, 50 to 60 affected Jewish children were born each year in the United States and Canada. After mass screenings began in 1971, the numbers declined to two to five Jewish births a year, said Karen Zeiger, whose first child died of Tay-Sachs.

In the days before Facebook or email, activists and organizers spread the word about mass Tay-Sachs screenings through newspaper and magazine articles, posters at synagogues, and items in Jewish organizational newsletters. (Courtesy of National Tay-Sachs and Allied Diseases Association/via JTA)

It had decreased significantly, said Zeiger, who until her retirement in 2000 was the State of Californias Tay-Sachs prevention coordinator. Between 1976 and 1989, there wasnt a single Jewish Tay-Sachs birth in the entire state, she said.

The first mass screening was held on a rainy Sunday afternoon in May 1971 at Congregation Beth El in Bethesda, Maryland. The site was chosen in part for its proximity to Johns Hopkins University in Baltimore. One of the two doctors who discovered the missing hexosaminidase A enzyme, John OBrien, was visiting a lab there, and another Johns Hopkins doctor, Michael Kaback, had recently treated two Jewish couples with Tay-Sachs children, including Zeigers. Zeigers husband, Bob, was also a doctor at Johns Hopkins.

The screenings used blood tests to check for the missing enzyme that identified a parent as a Tay-Sachs carrier.

With the help of 40 trained lay volunteers and 15 physicians, more than 1,500 people volunteered for testing and were processed through the system in about 5 hours, Dr. Kaback later recalled in an article in the journal Genetics in Medicine. For me, it was like having written a symphony and hearing it for the first time and it went beautifully, without glitches.

A machine to process the tests cost $15,000. We had bazaars, cake sales, sold stockings, and thats how we raised money for the machine, Zeiger said.

Before screening, couples in which both parents were Tay-Sachs carriers almost always stopped having children after they had one child with Tay-Sachs, for fear of having another, Ruth Schwartz Cowan wrote it in her book Heredity and Hope: The Case for Genetic Screening.

But with screening, Tay-Sachs could be detected before birth, and carrier couples felt encouraged to have children, she wrote.

People named their kids after him

Dr. Kabacks work helped enable thousands of parents who were Tay-Sachs carriers to have other, healthy children.

What he did for Tay-Sachs and how he helped so many families was amazing, Zeiger said. People named their kids after him.

The screenings were transformative, and the campaign to get Jews tested for Tay-Sachs took off. This was before the advent of Facebook or email, so activists and organizers spread the word about screenings through newspaper and magazine articles, posters at synagogues, and items in Jewish organizational newsletters. Volunteers and medical professionals spoke on college campuses and sent promotional prescription pads to rabbis, obstetricians, and gynecologists. Doctors and activists enlisted rabbis and community leaders to encourage couples to be tested before getting married.

Another early mass screening event was held at a school in Waltham, Massachusetts, guided by Edwin Kolodny, a professor at New York University medical school. The first mass screening in the Philadelphia area was on November 12, 1972, at the Germantown Jewish Center, and drew 800 people, according to a Yale senior thesis by David Gerber, Genetics for the Community: The Organized Response To Tay-Sachs Disease, 1955-1995.

Nearly half a century later, the Tay-Sachs screening effort remains a model for mobilizing a community against genetic disease. Parent activists, scientists and doctors are trying to emulate that model with other diseases and other populations.

You cant be complacent, because now there are 200 diseases you can test for

You cant be complacent, because now there are 200 diseases you can test for, said Kevin Romer, president of the Matthew Forbes Romer Foundation and a past president of the National Tay-Sachs and Allied Diseases Association. The foundation is named for Romers son Matthew, who died of Tay-Sachs in 1996.

Romer and others involved with this issue stress the importance of screening interfaith couples, too. Non-Jews may also benefit from pre-conception screening for Tay-Sachs and other diseases. Some research indicates, for example, that Louisiana Cajuns, French Canadians and individuals with Irish lineage may also have an elevated incidence of Tay-Sachs.

Heredity and Hope: The Case for Genetic Screening, by Ruth Schwartz Cowan. (Courtesy)

Scientific progress means that Jews can now be screened for over 200 diseases with an at-home, mail-in test offered by JScreen. The four-year-old nonprofit affiliated with Emory Universitys Department of Human Genetics has screened thousands of people, and the subsidized fee for the test about $150 includes genetic counseling.

While some genetic tests are standard doctors office procedure for pregnant women or couples trying to get pregnant with a doctors help, JScreen aims for pre-conception screening. The test includes diseases common in those with Ashkenazi, Sephardi, and Mizrahi backgrounds as well as general population diseases, making it relevant for Jewish couples and interfaith couples.

Carrier screening gives people an opportunity to plan ahead for the health of their future families. We are taking lessons learned from earlier screening initiatives and bringing the benefits of screening to a new generation, said Karen Arnovitz Grinzaid, executive director of JScreen. It was a path pioneered by the Tay-Sachs screening that began in 1971.

In Cowans book, she mentions a chart prepared by Dr. Kaback reporting on 30 years of screening: 1.3 million people screened, 48,000 carriers detected, 1,350 carrier couples detected, 3,146 pregnancies monitored.

Kaback and his colleagues could well have stopped there, she wrote. But they did not. There is one more figure, the one that matters most and that goes the furthest in explaining why Ashkenazi Jews accept carrier screening after monitoring with pre-natal diagnosis, 2,466 unaffected offspring were born to parents who were both Tay-Sachs carriers.

This article was sponsored by and produced in partnership with JScreen, whose goal of making genetic screening as simple, accessible, and affordable as possible has helped couples across the country have healthy babies. To access testing 24/7, request a kit at JScreen.org or gift a JScreen test as a wedding present. This article was produced by JTAs native content team.

Widespread testing is credited with helping reduce the incidence of Tay-Sachs among Jews by more than 90 percent since screenings began in the early 1970s. (Courtesy of National Tay-Sachs and Allied Diseases Association/via JTA)

Read more here:
How Jewish activism has wiped out Tay-Sachs - The Times of Israel