Monthly Archives: September 2021

Proteomics

The suffix "-ome" comes from the Greek for all, every, or complete. It was originally used in "genome," which refers to all the genes in a person or other organism. Due to the success of large-scale biology projects such as the sequencing of the human genome, the suffix "-ome" is now being used in other research contexts. Proteomics is an example. The DNA sequence of genes carries the instructions, or code, for building proteins. This DNA is transcribed into a related molecule, RNA, which is then translated into proteins. Proteomics, therefore, is a similar large-scale analysis of all the proteins in an organism, tissue type, or cell (called the proteome). Proteomics can be used to reveal specific, abnormal proteins that lead to diseases, such as certain forms of cancer.

Pharmacogenetics and Pharmacogenomics

The terms "pharmacogenetics" and "pharmacogenomics" are often used interchangeably in describing the intersection of pharmacology (the study of drugs, or pharmaceuticals) and genetic variability in determining an individual's response to particular drugs. The terms may be distinguished in the following way.

Pharmacogenetics is the field of study dealing with the variability of responses to medications due to variation in single genes. Pharmacogenetics takes into account a person's genetic information regarding specific drug receptors and how drugs are transported and metabolized by the body. The goal of pharmacogenetics is to create an individualized drug therapy that allows for the best choice and dose of drugs. One example is the breast cancer drug trastuzumab (Herceptin). This therapy works only for women whose tumors have a particular genetic profile that leads to overproduction of a protein called HER2. (See: Genetics, Disease Prevention and Treatment)

Pharmacogenomics is similar to pharmacogenetics, except that it typically involves the search for variations in multiple genes that are associated with variability in drug response. Since pharmacogenomics is one of the large-scale "omic" technologies, it can examine the entirety of the genome, rather than just single genes. Pharmacogenomic studies may also examine genetic variation among large groups of people (populations), for example, in order to see how different drugs might affect different racial or ethnic groups.

Pharmacogenetic and pharmacogenomic studies are leading to drugs that can be tailor-made for individuals, and adapted to each person's particular genetic makeup. Although a person's environment, diet, age, lifestyle, and state of health can also influence that person's response to medicines, understanding an individual's genetic makeup is key to creating personalized drugs that work better and have fewer side effects than the one-size-fits-all drugs that are common today. (See: Genetics, Disease Prevention and Treatment). For example, the U.S. Food and Drug Administration (FDA) recommends genetic testing before giving the chemotherapy drug mercaptopurine (Purinethol) to patients with acute lymphoblastic leukemia. Some people have a genetic variant that interferes with their ability to process this drug. This processing problem can cause severe side effects, unless the standard dose is adjusted according to the patient's genetic makeup. (See: Frequently Asked Questions about Pharmacogenomics).

Stem Cell Therapy

Stem cells have two important characteristics. First, stem cells are unspecialized cells that can develop into various specialized body cells. Second, stem cells are able to stay in their unspecialized state and make copies of themselves. Embryonic stem cells come from the embryo at a very early stage in development (the blastocyst staqe). The stem cells in the blastocyst go on to develop all of the cells in the complete organism. Adult stem cells come from more fully developed tissues, like umbilical cord blood in newborns, circulating blood, bone marrow or skin.

Medical researchers are investigating the use of stem cells to repair or replace damaged body tissues, similar to whole organ transplants. Embryonic stem cells from the blastocyst have the ability to develop into every type of tissue (skin, liver, kidney, blood, etc.) found in an adult human. Adult stem cells are more limited in their potential (for example, stem cells from liver may only develop into more liver cells). In organ transplants, when tissues from a donor are placed into the body of a patient, there is the possibility that the patient's immune system may react and reject the donated tissue as "foreign." However, by using stem cells, there may be less risk of this immune rejection, and the therapy may be more successful.

Stem cells have been used in experiments to form cells of the bone marrow, heart, blood vessels, and muscle. Since the 1990's, umbilical cord blood stem cells have been used to treat heart and other physical problems in children who have rare metabolic conditions, or to treat children with certain anemias and leukemias. For example, one of the treatment options for childhood acute lymphoblastic leukemia [cancer.gov] is stem cell transplantation therapy.

There has been much debate nationally about the use of embryonic stem cells, especially about the creation of human embryos for use in experiments. In 1995, Congress enacted a ban on federal financing for research using human embryos. However, these restrictions have not stopped researchers in the United States and elsewhere from using private funding to create new embryonic cell lines and undertaking research with them. The embryos for such research are typically obtained from embryos that develop from eggs that have been fertilized in vitro - as in an in vitro fertilization clinic - and then donated for research purposes with informed consent of the donors. In 2009, some of the barriers to federal financing of responsible and scientifically worthy human stem cell research were lifted.

Cloning

Cloning can refer to genes, cells, or whole organisms. In the case of a cell, a clone refers to any genetically identical cell in a population that comes from a single, common ancestor. For example, when a single bacterial cell copies its DNA and divides thousands of times, all of the cells that are formed will contain the same DNA and will be clones of the common ancestor bacterial cell. Gene cloning involves manipulations to make multiple identical copies of a single gene from the same ancestor gene. Cloning an organism means making a genetically identical copy of all of the cells, tissues, and organs that make up the organism. There are two major types of cloning that may relate to humans or other animals: therapeutic cloning and reproductive cloning.

Therapeutic cloning involves growing cloned cells or tissues from an individual, such as new liver tissue for a patient with a liver disease. Such cloning attempts typically involve the use of stem cells. The nucleus will be taken from a patient's body cell, such as a liver cell, and inserted into an egg that has had its nucleus removed. This will ultimately produce a blastocyst whose stem cells could then be used to create new tissue that is genetically identical to that of the patient.

Reproductive cloning is a related process used to generate an entire animal that has the same nuclear DNA as another currently or previously existing animal. The first cloned animals were frogs. Dolly, the famous sheep, is another example of cloning. The success rates of reproductive animal cloning, however, have been very low. In 2005, South Korean researchers claimed to have produced human embryonic stem cell lines by cloning genetic material from patients. However, this data was later reported to have been falsified.

Here is the original post:
Genetics vs. Genomics Fact Sheet - National Human Genome ...

Easter Islands famous megaliths have relatives on islands thousands of miles to the north and west, and so did the people who created them, a study has found.

Over a 250-year period separate groups of people set out from tiny islands east of Tahiti to settle Easter Island, the Marquesas and Raivavae archipelagos that are thousands of miles apart but all home to similar ancient statues.

These statues are only on those islands that are closely connected genetically, the studys lead author, Alexander Ioannidis of Stanford University, told AFP.

Ioannidis and his team were able to map and date the first Polynesians path of settlement, which began in Samoa and fanned out across the Pacific between the years 830 and 1360, using cutting-edge analysis of modern DNA.

This had been an open problem since Captain Cook first noticed that the people on the Polynesian islands were all speaking the same language, Ioannidis said.

The expansion happened rapidly over about 17 generations outpacing major changes in language or culture that could have served as markers, the findings show. The researchers were able to piece together the puzzle of trans-Pacific migration by comparing the genetic material in 430 present-day inhabitants across 21 islands.

The outward expansion from Samoa unfolded westward to Fiji, Tonga in the south, and then east to Rarotonga around the year 830.

A few hundred years later, descendants on Rarotonga travelled to settle present-day Tahiti and the Tuamotu archipelago just beyond. It is from the small, long-overlooked sand-bar islands of Tuamotu that the most ambitious forays set out, Ioannidis said.

Now sparsely populated, thanks in part to their role as nuclear test grounds, the Tuamotus span an area equal to the distance between England and Greece.

The study notes that the low-lying islands most likely emerged from below sea level only a few hundred years before Polynesians spread there.

They needed to have a maritime culture to get in between these small, ring-like islands, Ioannidis said. I think that explains in some part why it is from there that we see the longest-distance voyages going out.

This became ground zero for the megalith-building peoples who came to inhabit the Marquesas, Rapa Nui (Easter Island) and Raivavae.

The timing of those expansions fits with earlier DNA-based findings by Ioannidis and his team showing that Native Americans probably from the north-western coast of South America and Polynesians mingled around the year 1200.

The date we found for that contact is very close to the dates we find for these voyages out from the Tuamotus to settle these remote islands, Ioannidis said.

Todays Polynesian populations have mixed heritage, with traces of Europe, Africa and other places in their ancestry.

While genetic studies of ancient peoples have tended to focus on ancient DNA samples unearthed from archaeological sites, Ioannidis said his team had been able to home in on telltale sequences buried in modern DNA.

They used a software to analyse samples from 430 inhabitants across 21 different islands to identify recurring gene patterns specific to Polynesians, blocking out DNA sequences associated with European or other ancestry.

Otherwise, you would just find that the islands with the most Polynesian DNA were more related, Ioannidis said. Thats not interesting from a historical perspective.

His team used the genetic clues to draw a kind of family tree east to west across the Pacific.

DNA strands shorten as they are re-combined over generations, therefore the length of shared segments revealed how many generations passed between each settlement.

Read more from the original source:
Genetics reveal how humans island-hopped to settle remote Pacific - The Guardian

Although some hoped having the human genome in hand [as of two decades ago] would let us sprint to medical miracles, writesScienceSenior Editor Laura Zahn, in an introduction to a special issue of the journal, the field is more an ongoing relay race of contributions from genomic studies. In a Policy Forum, a Perspective, four Reviews and two related News stories, the special issue examines well-earned successes in applying research in the human genome to understanding human evolution, cancer, polygenic traits, and functional genomics. It also highlights research ground yet to cover.

A Perspective in the issue by Jennifer E. Rood and Aviv Regev reflects on the progress since the publication of the first draft sequence of the Human Genome Project (HGP). The initiative forever altered biomedicine, they say, but work remains to fulfill its true potential. The HGP has also left us with a major missionstill incomplete 20 years laterto understand how genomic information leads to the development, function, and malfunction of cells and organisms and to fully leverage this knowledge to promote human health and treat disease, say Rood and Regev.

In a Policy Forum, Natalie Ram and colleagues highlight thefirst law in the United Statesand in the worldthat comprehensively regulates law enforcements use of consumer genetic data to investigate crimes. It was enacted in May 2021 in Maryland. Before that, the primary restraint on law enforcements use of consumer genetic data had come from consumer genetics platforms themselves, with some declining to cooperate. The new laws success, say the authors, provides a roadmap for regulating genetic genealogy in a way that balances privacy and public safety, and its terms include six critical features that others should model moving forward.

Four Reviews cover topics including the value of the polygenic (risk) score for identifying people at increased risk of disease, thereby facilitating prevention or early intervention; the importance of integrating different types of data in understanding the molecular evolution of malignant cell states across the cancer life cycle; the importance of understanding the biological mechanisms by which genetic variants influence phenotypes, using new methods; and the way recent advancements in DNA sequencing technologies and laboratory preparation protocols have expanded the scope of ancient DNA research over the past decade.

A story from Jocelyn Kaiser, a reporter inSciencesnews department, reviews the promise of newborn genome sequencing, which still faces a host of ethical and practical obstacles. Even so, one company in the United Kingdom is pushing ahead with a major test: Genomics England is planning a large pilot research project, involving as many as 200,000 babies. In a separate news story on human genomics, reporter Mitch Leslie profiles researcher and physician Dan Kastner, who became the scientific director of the National Human Genome Research Institute in 2010. Kastner isknown for having defined autoinflammatory diseases as a category of illness, and for having collaborated to identify 14 defective genes that trigger these conditions. By identifying what drives these diseases, Kastners work opened the door for life-changing and even life-saving treatments for patients.Whats more, the gene-hunting methods he and other scientists have pursued could change the approach for identifying and defining diseases; doctors have traditionally recognized new illnesses based on clusters of symptoms, but Kastner proposes to first sequence genomes to pinpoint mutations and then determine if people who carry these glitches suffer from unexplained health problems. This approach could allow for discovery of diseases scientists didnt imagine occurring, Leslie writes. In fact, Kastner and his colleagues have already revealed one such unimagined disease, and he plans to search for more.

A Research Ultramarathon

24-Sep-2021

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Continued here:
Special issue: Applying research in the human genome -- progress and potential - EurekAlert

Sep 25th 2021

THE COLONISATION of the Pacific Ocean was one of the great feats of human navigation. Groups of a few dozen people, travelling in canoes carved from trees, discovered and settled hundreds of tiny islands separated by vast spans of open water. They found their way using the stars, dead reckoning and study of the wind.

Your browser does not support the

Enjoy more audio and podcasts on iOS or Android.

Exactly when these trips occurred, and in which order, is unclear. Oral histories are richly detailed, but vague on dates. The colonisers moved too fast for linguistic analysis to yield answers. Archaeological evidence is scant. But a new paper by Alex Ioannidis of Stanford University and 26 other scholars claims to have clarified this fuzzy history using genetics, by analysing the DNA of 430 modern-day Polynesians.

Polynesian prehistory reaches back to the island now called Taiwan. From there, starting in around 2500BC, the ancestors of todays Pacific Islanders are thought to have spread through the Philippines and Indonesia to western Polynesian islands such as Samoa and Fiji. They paused there for centuries or more, before venturing on to the vast emptiness of the Pacific. The authors focus on this second expansion.

The team relied on a genetic pattern called the founder effect. Each canoe probably carried only a few dozen people, out of hundreds or thousands living on the originating island. These pioneers descendants should thus be less genetically diverse than people on the island from which their ancestors came. Every subsequent colonisation should have created a new genetic bottleneck. The authors determined the order of the voyages by finding this signature in modern genomes, while excluding confounding chunks of DNA contributed by later arrivals from Europe.

The dates are less certain than the sequence. Genomics counts time in generations, not years. However, research on other places in pre-modern time periods, such as 17th-century Iceland and rural Quebec in the 1800s, suggests an average generation length of 30 years.

The study shows that the Polynesians moved quickly once they set out into open ocean. One of the first colonisation voyages probably set off in around 830AD from Samoa to Rarotongathe largest of the Cook Islands, a 67-square-kilometre speck about 1,500km to the south-east. By 1050, explorers seem to have reached Tahiti. Just 50 years later, they had probably set foot in the Tuamotu Islands, a 1,500km-long series of tiny atolls. A heroic 2,600km journey from Mangareva to Easter Island, one of the remotest dots of land on the planet, is likely to have occurred in around 1210.

This chronology is of course inexact. However, the authors are confident in the sequence, and say that the total dating error should be only around 60 years. Moreover, their account is compatible with both archaeological records and Polynesians own oral histories. For those who know how to read it, the history of the Polynesian voyagers lives on in their descendants.

Source: Paths and timings of the peopling of Polynesia inferred from genomic networks, by A.G. Ioannidis et al., Nature, 2021

This article appeared in the Graphic detail section of the print edition under the headline "To the ends of the Earth"

Visit link:
Genes reveal how and when humans reached remote corners of Pacific - The Economist