Category Archives: Human Genetics

A cell programming technique developed at the Weizmann Institute turns them into the earliest precursors of sperm and ova

IMAGE:These are clusters of human embryonic stem cells that were differentiated to an early germ cell (PGC) state (colored cells). Each color reveals the expression of a different gene. (l-r)... view more

Credit: Weizmann Institute of Science

Groups at the Weizmann Institute of Science and Cambridge University have jointly managed the feat of turning back the clock on human cells to create primordial germ cells - the embryonic cells that give rise to sperm and ova - in the lab. This is the first time that human cells have been programmed into this early developmental stage. The results of their study, which were published today in Cell, could help provide answers as to the causes of fertility problems, yield insight into the earliest stages of embryonic development and potentially, in the future, enable the development of new kinds of reproductive technology.

"Researchers have been attempting to create human primordial germ cells (PGCs) in the petri dish for years," says Dr. Jacob Hanna of the Institute's Molecular Genetics Department, who led the study together with research student Leehee Weinberger. PGCs arise within the early weeks of embryonic growth, as the embryonic stem cells in the fertilized egg begin to differentiate into the very basic cell types. Once these primordial cells become "specified," they continue developing toward precursor sperm cells or ova "pretty much on autopilot," says Hanna. The idea of creating these cells in the lab took off with the 2006 invention of induced pluripotent stem (iPS) cells - adult cells that are "reprogrammed" to look and act like embryonic stem cells, which can then differentiate into any cell type. Thus several years ago, when researchers in Japan created mouse iPS cells and then got them to differentiate into PGCs, scientists immediately set about trying to replicate the achievement in human cells. But until now, none had been successful.

Previous research in Hanna's lab pointed to new methods that could take human cells to the PGC state. That research had focused on the question of how human iPS cells and mouse embryonic cells differ: The mouse embryonic cells are easily kept in their stem cell state in the lab, while human iPS cells that have been reprogrammed - a technique that involves the insertion of four genes - have a strong drive to differentiate, and they often retain traces of "priming." Hanna and his group then created a method for tuning down the genetic pathway for differentiation, thus creating a new type of iPS cell that they dubbed "nave cells." These nave cells appeared to rejuvenate iPS cells one step further, closer to the original embryonic state from which they can truly differentiate into any cell type. Since these nave cells are more similar to their mouse counterparts, Hanna and his group thought they could be coaxed to differentiate into primordial germ cells.

Working with nave human embryonic stem and iPS cells, and applying the techniques that had been successful in the mouse cell experiments, the research team managed to produce cells that, in both cases, appeared to be identical to human PGCs. Together with the lab group of Prof. Azim Surani of Cambridge University, the scientists further tested and refined the method jointly in both labs. By adding a glowing red fluorescent marker to the genes for PGCs, they were able to gauge how many of the cells had been programmed. Their results showed that quite a high rate - up to 40% - had become PGCs; this quantity enables easy analysis.

Hanna points out that PGCs are only the first step in creating human sperm and ova. A number of hurdles remain before labs will be able to complete the chain of events that move an adult cell through the cycle of embryonic stem cell and around to sperm or ova. For one, at some point in the process, these cells must learn to perform the neat trick of dividing their DNA in half before they can become viable reproductive cells. Still, he is confident that those hurdles will one day be overcome, raising the possibility, for example, of enabling women who have undergone chemotherapy or premature menopause to conceive.

In the meantime, the study has already yielded some interesting results that may have significant implications for further research on PGCs and possibly other early embryonic cells. The team managed to trace part of the genetic chain of events that directs a stem cell to differentiate into a primordial germ cell, and they discovered a master gene, Sox17, that regulates the process in humans, but not in mice. Because this gene network is quite different from the one that had been identified in mice, the researchers suspect that more than a few surprises may await scientists who study the process in humans.

Hanna: "Having the ability to create human PGCs in the petri dish will enable us to investigate the process of differentiation on the molecular level. For example, we found that only 'fresh' nave cells can become PGCs; but after a week in conventional growth conditions they lose this capability once again. We want to know why this is. What is it about human stem cell states that makes them more or less competent? And what exactly drives the process of differentiation once a cell has been reprogrammed to its more nave state? It is the answers to these basic questions that will, ultimately, advance iPS cell technology to the point of medical use."

Excerpt from:
Human primordial cells created in the lab

At least six million Americans who identify themselves as white have more "black" DNA than white people in other parts of the United States, according to a recent study published in the American Journal of Human Genetics. Several states, which have been the focal points of racial tensions in the U.S. over the years, are made up of self-described white people whose ancestors are black, the study claims.

Researchers reportedly examined the genetic records of 145,000 people who submitted saliva samples -- where DNA sequence variations are found -- to 23andMe, a California-based private company that provides ancestry-related genetic reports. From the data, researchers determined that people especially from the South have at least 1 percent of African ancestry. The study also found that states with the highest levels of African ancestry, such as South Carolina, Georgia, and Florida, are not those with the highest proportions of African Americans.

European Americans with African ancestry comprise as much as 12 percent of European Americans from Louisiana and South Carolina and about 1 in 10 individuals in other parts of the South, according to the study.

The study also showed that people with less than 28 percent African ancestry identified themselves as European American, and not as African-American. Only people with morethan 50 percent African ancestryidentified themselves as African-American, The Washington Post reported, citing the survey. In addition, the studyfound that African-Americans are more likely to have a European male ancestor (19 percent) than a European female one (5 percent).

"Our study not only reveals the historical underpinnings of regional differences in genetic ancestry, but also sheds light on the complex relationships between genetic ancestry and self-identified race and ethnicity," study author Katarzyna Bryc of 23andMe reportedly said, in a press release.

Follow this link:
White Southerners Likely To Have More Black DNA Than Whites Elsewhere In The US: Study

Stem Cells: Tools for Human Genetics and Heart Regeneration
Department of Medicine Grand Rounds presentation by Dr. Charles Murry, professor, Department of Pathology, Bioengineering and Medicine/Cardiology; Director, ...

By: UWDeptMedicine

Follow this link:
Stem Cells: Tools for Human Genetics and Heart Regeneration - Video

HERBERT THE PERVERT (The Hidden Source)
Enjoy the video? Subscribe! http://bit.ly/SubToSeaNanners What is The Hidden? "In the early 1950s human genetics experimentation was taking its first, tent...

By: SeaNanners Gaming Channel

See the original post here:
HERBERT THE PERVERT (The Hidden Source) - Video

Published 22 December 2014

NewLink Genetics and Merck announced that the Biomedical Advanced Research and Development Authority (BARDA) of the United States Department of Health and Human Services (HHS) has awarded a contract to manufacture Ebola vaccine candidate.

NewLink Genetics' wholly-owned subsidiary, BioProtection Systems, is the prime contractor in a $30 million contract to support the manufacturing and development activities of its investigational rVSV-EBOV (Ebola) vaccine candidate, including clinical development through a new 330-person Phase Ib study.

The vaccine candidate was initially developed by the Public Health Agency of Canada (PHAC), and is now being developed under an exclusive licensing and collaboration agreement between NewLink Genetics and Merck. The rVSV-EBOV (Ebola) vaccine candidate is currently being evaluated in Phase I clinical studies in humans.

"The current funding provided by BARDA is key to the rapid development of this Ebola vaccine candidate. These funds will support multiple facets of the accelerated Ebola vaccine program including the expansion of critical vaccine supplies and larger clinical studies," said Dr. Charles Link, CEO and Chief Scientific Officer of NewLink Genetics.

"Governments and industry are effectively collaborating in an unprecedented effort to accelerate the development of Ebola vaccine candidates," said Dr. Mark Feinberg, chief public health and science officer of Merck Vaccines. "If we can bring an efficacious and well-tolerated vaccine to the outbreak countries, we will not only help protect people at risk in the current crisis, but also may help reduce the likelihood of such tragic events in the future."

Pending the results of Phase I trials underway, the US National Institutes of Health has announced plans to initiate, in early 2015, a large randomized, controlled Phase II/III study to evaluate the safety and efficacy of this and another investigational Ebola vaccine candidate.

Read more:
NewLink Genetics, Merck receive grant to manufacture Ebola vaccine candidate

Contact Information

Available for logged-in reporters only

North Dakota State University, Fargo, and Sanford Health will conduct collaborative research on human nutrition, weight management and other dietary-related areas as part of a seed-grant initiative developed between the two organizations. The research will address key objectives of the Profile by Sanford program.

Profile is a weight-management program that uses customized meal plans, health coaches and real-time technology. It was developed by Sanford physicians and researchers.

NDSU researchers will have opportunities to collaborate with investigators from Sanford Research on topics like metabolism, food choices and consumption, prenatal nutrition, genetics, development of sensors that monitor wellness factors and food manufacturing and nutritional interactions with the human microbiome. Research findings relevant to Profile will be considered as the program evolves and expands.

Sanford will provide $250,000 annually for five years for the seed-grant program.

This collaboration with Sanford represents additional opportunities for faculty to conduct research with potential wide-ranging implications for positive impact on human health, said NDSU President Dean L. Bresciani.

Sanford Health was named as the first Campus Community Partner in 2012, to recognize private sector collaborations with the university that benefit the community, said President Bresciani. Adding this research collaboration to our already strong partnership to train nurses in the region, further illustrates our commitment to the communities we serve.

The Profile system utilizes meal-replacement products, nutritionally complete foods, qualified health coaches and client tracking of body weight, blood pressure and physical activity through smart wireless technology. Jawbone UP24 activity trackers are integrated with the Profile app to allow members to track their movement and sleep patterns. A new fitness tracker will provide additional measurable data helpful to members to monitor progress.

This collaboration offers an additional opportunity to further serve the citizens of the region, while potentially making strides that contribute to important research on health and well-being, said Kelly A. Rusch, NDSU vice president for research and creative activity.

Read more:
NDSU, Sanford Health Announce Research on Human Health, Nutrition

VIDEO:This is a scan of a femur and comparison of gracile and robust tribecular bone in the femur head. view more

The comparatively light bone structure of modern humans compared to early human species and other modern primates may be due to the modern abandonment of the constant physical activity that was inherent in the life of early hunter gathers, according to an international team of researchers. This knowledge may aid in prevention of osteoporosis and hip fracture in the elderly.

"We set out to test three potential explanations for modern human gracility and any one of them would have been interesting," said Timothy M. Ryan, associate professor of anthropology and information science and technology, Penn State. "What we found was the most interesting."

The most plausible explanation, he said, is that a lack of constant physical activity causes the bone in the head of the femur -- the long bone in the thigh -- to become thinner and lighter than that found in more mobile populations or modern primates such as chimpanzees, gorillas and orangutans. The other two possible explanations, that humans and nonhuman primates have different bone structure because of genetics, with humans evolving to a lighter, more gracile structure, or that the large joint surfaces required for upright, two-legged movement decrease the strain on bone and therefore the development of strong bones, do not appear to be true.

Ryan, working with Colin N. Shaw of the University of Cambridge, UK, looked at the hip joint to determine which of the three possible explanations was likely. They compared these joints in samples from foraging populations, early agriculturalists and comparably sized nonhuman primates. The human bones came from two agricultural groups and two foraging groups that once lived in what is now Illinois. The nonhuman bones came mostly from wild specimens in collections.

The researchers used noninvasive microcomputed tomography to scan the hip joint ends of the femurs. In all, the study included 59 adult humans and 229 nonhuman primates. Ryan and Shaw compared the trabecular bone -- the honeycomb-like bone that fills joint ends -- among the three groups.

"The results of the present study indicate that human populations with divergent activity patterns display significantly different trabecular bone structural characteristics in the proximal femur," the researchers report online today (Dec 22) in the Proceedings of the National Academy of Sciences.

The researchers found that the agriculturalists had significantly lower bone mass than the foragers. However, the bone characteristics of the more mobile foragers overlapped with those of the nonhuman primates.

"There are other things that could account for some of the differences between early agriculturalists and foragers," said Ryan. "The amount of cultivated grains in the diet of the agriculturalists, in this case maize, as well as possible deficiencies in dietary calcium may also contribute to lower bone mass. It does seem, however, that the biomechanical aspects of foraging play a large part."

"The findings of the present study have significant implications for understanding human skeletal form and its relationship to age-related bone loss in contemporary human populations," the

Read more:
Fragile bones of modern humans result from reduced physical activity

Image: DEMIS Mapserver/Wikimedia commons

Many Americans who identify as European actually carry African ancestry just as many Americans who identify as African carry European ancestry, finds an extensive new genetic analysis.

DNA tells no lies, so the findings, published in the American Journal of Human Genetics, reveal just what a melting pot of different racial and ethnic groups exists in the United States.

"Our study not only reveals the historical underpinnings of regional differences in genetic ancestry, but also sheds light on the complex relationships between genetic ancestry and self-identified race and ethnicity," study author Katarzyna Bryc of 23andMe and Harvard Medical School said in a press release.

Bryc and her team studied DNA sequence variations called "single-nucleotide polymorphisms" in the genomes of more than 160,000 African Americans, Latinos and European Americans. Study participants provided saliva samples, where the DNA sequence variations were found.

The researchers found that more than 6 million Americans who self-identify as European likely carry African ancestry. As many as 5 million self-described European Americans might have at least 1% Native American ancestry, according to the study.

The researchers also determined that regional ancestry differences reflect historical events in the U.S., such as waves of immigration. For example, Scandinavian ancestry is found in trace proportions in most states, but it makes up about 10% of ancestry in European Americans living in Minnesota and the Dakotas.

The scientists also discovered that people identify roughly with the majority of their genetic ancestry.

Couples share similar genetics

Nevertheless, racial lines appear to be more blurred than previously thought.

See the original post here:
Genetic study shows how much America really is a melting pot

PUBLIC RELEASE DATE:

18-Dec-2014

Contact: Megan McRainey megan.mcrainey@emory.edu 404-727-6171 Emory Health Sciences @emoryhealthsci

Many genetic mutations in visual pigments, spread over millions of years, were required for humans to evolve from a primitive mammal with a dim, shadowy view of the world into a greater ape able to see all the colors in a rainbow.

Now, after more than two decades of painstaking research, scientists have finished a detailed and complete picture of the evolution of human color vision. PLOS Genetics is publishing the final pieces of this picture: The process for how humans switched from ultraviolet (UV) vision to violet vision, or the ability to see blue light.

"We have now traced all of the evolutionary pathways, going back 90 million years, that led to human color vision," says lead author Shozo Yokoyama, a biologist at Emory University. "We've clarified these molecular pathways at the chemical level, the genetic level and the functional level."

Co-authors of the PLOS Genetics paper include Emory biologists Jinyi Xing, Yang Liu and Davide Faggionato; Syracuse University biologist William Starmer; and Ahmet Altun, a chemist and former post-doc at Emory who is now at Fatih University in Istanbul, Turkey.

Yokoyama and various collaborators over the years have teased out secrets of the adaptive evolution of vision in humans and other vertebrates by studying ancestral molecules. The lengthy process involves first estimating and synthesizing ancestral proteins and pigments of a species, then conducting experiments on them. The technique combines microbiology with theoretical computation, biophysics, quantum chemistry and genetic engineering.

Five classes of opsin genes encode visual pigments for dim-light and color vision.

Bits and pieces of the opsin genes change and vision adapts as the environment of a species changes.

See the original post here:
A clear, molecular view of how human color vision evolved

PUBLIC RELEASE DATE:

18-Dec-2014

Contact: Mary Clarke press.office@sanger.ac.uk 44-122-349-2368 Wellcome Trust Sanger Institute @sangerinstitute

A study of the way malaria parasites behave when they live in human red blood cells has revealed that they can rapidly change the proteins on the surface of their host cells during the course of a single infection in order to hide from the immune system.

The findings, which overturn previous thinking about the Plasmodium falciparum parasite's lifecycle, could explain why so many attempts to create an effective vaccine have failed and how the parasites are able to survive in the human body for such long periods of time.

In the study, Plasmodium falciparum parasites were kept dividing in human blood for over a year in the laboratory, with the full parasite genome being sequenced regularly. This gave the scientists snapshots of the parasite's genome at multiple time points, allowing them to track evolution as it unfolded in the lab. They found that the 60 or so genes that control proteins on the surface of infected human blood cells, known as var genes, swapped genetic information regularly, creating around a million new and unrecognisable surface proteins in every infected human every two days.

"These genes are like decks of cards constantly being shuffled," explains William Hamilton, a first author from the Wellcome Trust Sanger Institute. "The use of whole genome sequencing and the sheer number of samples we collected gave us a detailed picture of how the var gene repertoire changes continuously within red blood cells."

The results show, for the first time, that the process of swapping genetic information, known as recombination, happens not when the malaria parasite is inside the mosquito, as previously thought, but during the asexual stage of the parasite's lifecycle inside human blood cells. This may go some way to explaining how chronic asymptomatic infection, a crucial problem for malaria elimination, is possible.

"It's very likely that mosquitos are re-infected with Plasmodium falciparum parasites at the beginning of each wet season by biting humans who have carried the parasites, often asymptomatically, for up to eight months during the dry season," says Dr Antoine Claessens, a first author from the Malaria Programme at the Wellcome Trust Sanger Institute. "During those months the parasite's var genes are busy recombining to create millions of different versions - cunning disguises that mean they remain safe from the immune system and ready for the new malarial season."

While further work will be required to fully understand the mechanism driving the recombination of Plasmodium falciparum's var genes, scientists were able to calculate the rate at which it happens. They found that var gene recombination takes place in about 0.2 per cent of parasites after each 48-hour life cycle in the red blood cell. With about a billion parasites living inside a typical infected human, there is huge potential for the parasite to create new, recombined var genes inside each person with malaria. This pace of change far exceeds that of genes in any other region of the parasite's genome.

See more here:
Fast-changing genes help malaria to hide in the human body