Thursday, June 09, 2016

Ginkgo Bioworks Raises $100 Million To Use Synthetic Biology To Design Microbes For Industry

Ginkgo Bioworks, a Boston-based startup that says it is the biggest consumer of synthetic DNA on the planet, just nabbed a big payday. The plan: custom-design living cells for companies in the fragrance, flavor and food industries.
 Ginkgo announced this morning that it has raised $100 million from investors including including Y Combinator’s Continuity Fund, Senator Investment Group, Cascade Investment, Baillie Gifford, Viking Global Investors and Allen & Company LLC. It also says it is buying a huge amount of DNA–600 million base pairs–from the two major manufacturers of synthetic DNA sequence: Gen9 and Twist Bioscience. That’s about 600,000 genes worth of material, and 60% of the total amount of synthetic DNA sold in 2015. The price of this raw genetic material has been dropping precipitously, making it more possible to engineer microbes like bacteria and yeast.
 There's a more detailed post on Forbes that you can read here
Ginkgo was founded in 2008, the brainchild of a group of MIT Ph.D.’s and their mentor, Tom Knight.  For years they worked carefully, using robotics and other techniques to make creating designer organisms more like manufacturing and less like making a bespoke suit. In 2014, Ginkgo became a Y Combinator company and started a streak of fundraising that, including today’s round, has brought the company $154 million. 

Monday, February 16, 2015

Stem Cells May Hold Key to Reversing Hair Loss

The medical term for hair loss is alopecia. It's a blanket term referring to any kind of hair loss. Loss of hair can be due to a number of reasons, caused by a number of factors ranging from the environment to genetics. Androgenetic alopecia, more commonly known as male or female pattern baldness, is the most common form of hair loss. For alopecias non-androgenetic in nature, cases of scarring alopecia, ringworm, telogen effluvium, alopecia areata and hair loss as a result of cosmetic overprocessing are most commonly seen by dermatologists.

Compared to other health conditions, hair loss and other hair diseases get very little attention, resulting in sparse research which yields very few solutions to those suffering from them. Hair research still has ways to go but the great strides Terskikh and colleagues took with their work on stem cells and hair transplants offer a lot of hope for those dealing with alopecia.

The researchers came up with a means to coax human pluripotent stem cells into becoming dermal papilla cells, a unique group of cells responsible for regulating the formation and growth of hair follicles. On their own, dermal papilla cells are not ideal for transplants because they are not able to sustain their ability to induce the formation of hair follicles in culture and are simply not available in enough amounts.

Autoimmune Diseases Linked To Genomic Switches

Researchers at the National Institutes of Health have now discovered certain genomic switches in blood cells that may be key to regulating the human immune system.
Senior study author John J. O'Shea, M.D., and the scientific director at NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases studied how the immune system can mistakenly attack its own cells, resulting in inflammation.

Many autoimmune diseases occur when the immune system mistakenly attacks its own cells, resulting in inflammation that can result in different health problems. Though the causes of many autoimmune diseases are not well understood, scientists believe that they have a genetic component because they often run in families.

However, identifying an autoimmune disease isn't always so simple. Some genes have been found in regions of DNA that the genes do not carry. Furthermore, scientists have suspected that the variants are in DNA elements called enhancers that act as switches to help control various gene activities.
Researchers began searching for super-enhancers (SEs) in T cells, otherwise known as immune cells that play a critical role in rheumatoid arthritis. SEs could serve as signposts to steer them toward potential genetic risk factors for the disease, according to the study.

"Rather than starting off by looking at genes that we already knew were important in T cells, we took an unbiased approach," the researchers concluded. "From the locations of their super-enhancers, T cells are telling us where in the genome these cells invest their assets--their key proteins--and thereby where we are most likely to find genetic alterations that confer disease susceptibility."

read the entire article here

Whole-Genome Sequencing Now Possible for IVF

Since the first in vitro fertilization (IVF) birth in 1978 more than 5 million babies have been born using this method. In order to alleviate added stress for couples already experiencing difficulties to conceive, fertility scientists utilize pre-implantation genetic diagnosis (PGD) techniques to detect large chromosomal abnormalities or gene mutations that are passed along by parents to the IVF embryos.      

Unfortunately, it is not possible to systematically scan the entire genome of the embryo in order to detect spontaneous mutations. However, scientists from Complete Genomics, Reprogenetics, and the NYU Fertility Center believe they may have solved that problem.

Scientists from the collaboration have developed a whole-genome sequencing method that uses 5- to 10-cell biopsies from the in vitro embryos to scan for potentially detrimental mutations.    
The results from this study were published online in Genome Research in an article entitled "Detection and phasing of single base de novo mutations in biopsies from human in vitro fertilized embryos by advanced whole-genome sequencing".

Investigators sequenced three biopsies from two IVF embryos and searched for de novo mutations, those that emerge spontaneously in the egg or sperm and are not inherited by parental genes. Spontaneous mutations are believed to play a significant role in many congenital disorders such as autism, epilepsy, and some severe forms of intellectual disability.  

"Because each individual carries on average less than 100 de novo mutations, being able to detect and assign parent of origin for these mutations, which are the cause of many diseases, required this extremely low error rate," said co-authors Brock Peters, Ph.D., director of research and Radoje Drmanac, Ph.D., CSO at Complete Genomics.

you can read the entire article here:

Your love for chocolates may have something to do with your genes!

It turns out that whether you like dark chocolate or milk chocolate may have a little bit to do with your genetics.

We know that our bitter and sweet taste perceptions are highly associated with different genetic variants.
A lot of work has focused specifically on bitter taste perception associated with a variant in the TAS2R38 gene. Some people have it and some don’t.
About a quarter of 23andMe customers don’t have the bitter taste variant — making them more likely to have a taste for hoppy beer, broccoli or dark chocolate. A variant in theTAS2R38 gene enables some to perceive the bitterness of the chemical propylthiouracil, or PROP. Some so-called supertasters not only perceive bitterness but also can discern more saltiness, sweetness and spice, suggesting that there are other genes involved in food our food preference.
So of course the TAS2R38 variant doesn’t explain everything. While surveys of in the United States show that more than half of Americans prefer milk chocolate to dark, among 23andMe customers dark chocolate wins out. Almost half of 23andMe customers prefer dark chocolate, while about 39 percent say they like milk chocolate. That may have to do with genetics, but it is more likely related to a mix of other non-genetic factors.
And there are plenty of genetic factors that researchers are still exploring. For instance, a genome wide association study done last year found 17 genes related to liking certain foods — including among other things dark chocolate, blue cheese and liver — that belong to the groups of genes that apparently have nothing to do with taste or smell perception.

All this just goes to show that, like love, our food preferences are complicated.

you can read the original article here:

Thursday, June 19, 2014

Next Gen Sequencing Applications

Next-Generation Sequencing: Methodology and Application

Next-generation sequencing (NGS), also known as high-throughput sequencing, is the catch-all term used to describe a number of different modern sequencing technologies including:
  • Illumina (Solexa) sequencing
  • Roche 454 sequencing
  • Ion torrent: Proton / PGM sequencing
  • SOLiD sequencing
These recent technologies allow us to sequence DNA and RNA much more quickly and cheaply than the previously used Sanger sequencing, and as such have revolutionised the study of genomics and molecular biology.

Everyone knows by now that the applications of NGS or Nex-Generation Sequencing, has already proved worthy of it's time, effort and applications. Most recently, in the news:

Next-gen sequencing IDs rare infection, saves boy's life

A 14 year old boys life was saved thanks to NGS or Next Gen Sequencing.

The sample came from a 14-year-old Wisconsin boy with dangerous swelling in his brain. His doctors, not sure that he'd survive the weekend, sent the sample with the thin hope that Chiu's team might figure out what was making him sick, and solve a months-long mystery.
In just two days, using experimental genomic sequencing technology, Chiu had an answer: leptospira. It's a rare bacterial infection - so rare that it would eventually take the U.S. Centers for Disease Control four months to confirm the diagnosis - that fortunately for the boy was very treatable.

 To solve the mystery, Chiu's team used a diagnostic tool known as "next-generation sequencing," which allows scientists to very quickly read and analyze the genetic makeup of an organism. Their rapid diagnosis of Joshua was one of the first examples of using the sequencing technology in a setting outside a lab.

And, scientists say, it may be the first time the tool has saved a life. The case was written up in a paper published this month in the New England Journal of Medicine.

"I feel the diagnosis could not have been made in this boy's case without next-generation sequencing. It definitely wouldn't have been in time," said Chiu, the paper's senior author and head of the viral diagnostics laboratory at UCSF.

You can read the whole article here

Sunday, April 06, 2014

A Conversation With 23andMe’s Joanna Mountain

This interview is part of an occasional series of profiles introducing you to the people behind 23andMe’s compelling research. Early in her career, Joanna Mountain, 23andMe’s Senior Director of Research studied the language and genetic diversity in Kenya. At 23andMe, Joanna still studies the genetic diversity of Africa, most recently as part of our African Ancestry projects, but she also spends time investigating how people react to their genetic results.

“Each tiny segment of the genome has a history.”

What are you working on at 23andMe?
One of my current areas of interest is learning more about how having access to genetic test results impacts people’s lives. We wanted to know how customers reacted to their genetic risk for breast cancer, for example, and what we found is that the test results prompted people to take positive steps, including talking to their doctors and discussing the results with family members. We’re currently looking at similar research in people with genetic risk of venous thromboembolism.

Our team is also researching genetic factors that influence how people respond to medications. Preliminary findings show that people report a very short list of side effects to a variety of drugs, with the most common being hives and stomach pain. My colleague, David Hinds presented on the topic of opioid-induced vomiting at last year’s American Society of Human Genetics meeting in Boston and we expect to publish further research this year.

How does your research in Africa apply to your work at 23andMe?
I am very interested in the great depth of genetic diversity in African populations. Because our species has lived in Africa for so long, it impacts our ability to tell African Americans where their ancestors are from. Many African Americans hit a brick wall when they start researching their genealogy, but where there aren’t paper records, we hope genetics will be able to fill in the gaps.

Why are you excited about genetics?
I was first studying applied math, and there’s a lot of math in population genetics. Being able to predict what will happen over the course of generations is a cool application of math, and I was initially drawn to that.

Tell us about a recent breakthrough in genetics research that you think will have a big impact.
Today, huge numbers of people are participating in genetic research. By providing researchers with information about your health and ancestry, we can do so much. We’re getting closer to understanding human prehistory and the genetic factors and history of disease, for example. 23andMe’s customers contribute to that, and future generations will benefit in the long run.

Read the whole article here:

Sunday, August 25, 2013

New Tool Enhances the Search for Genetic Mutations

Concealed within the vastness of the human genome, (composed of some 3 billion base pairs), mutations are commonplace. While the majority of these appear to have neutral effect on human health, many others are associated with diseases and disease susceptibility.

Reed Cartwright, a researcher at Arizona State University's Biodesign Institute, along with colleagues at ASU, Washington University and the Wellcome Trust Sanger Institute, Cambridge, UK, report on a new software tool known as DeNovoGear, which uses statistical probabilities to help identify mutations and more accurately pinpoint their source and their possible significance for health.

Improvements in the accuracy of mutation identification and validation could have a profound impact on the diagnosis and treatment of mutation-related diseases.

"These techniques are being considered in two different realms," Cartwright says. "The first is for pediatric diseases." Here, a child with an unusual genetic disease may undergo genomic sequencing to see if the mutations observed have been acquired from the parents or are instead, unique to the child. "We can identify these mutations and try to detect which gene may be broken," he says.

The second application is for cancer research, where tumor tissues are genetically compared with normal tissue. Many now believe that the identification of a specific cancer mutation may eventually permit clinicians to customize a treatment for that tissue type. "We are developing methods to allow researchers to make those types of analyses, using advanced, probabilistic methods," Cartwright says. "We actually model the whole process."

Indeed, the method described provides the first model-based approach for ferreting out certain types of mutations. The group's research results appear in today's issue of the journal Nature Methods.

One of the primary goals in genetics is to accurately characterize genetic variation and the rate at which it occurs. Searching for DNA mutations through genetic sequencing is an important ingredient in this quest, but many challenges exist. The current study focuses on a class of mutations that play a critical role in human disease, namely de novo mutations, which arise spontaneously and are not derived from the genomes of either parent.

Traditionally, two approaches for identifying de novo mutation rates in humans have been applied, each involving estimates of average mutations over multiple generations. In the first, such rates are measured directly through an estimation of the number of mutations occurring over a known number of generations. In the second or indirect method, mutation rates are inferred by estimating levels of genetic variation within or between species.

In the new study, a novel approach is used. The strategy, pioneered in part by Donald Conrad, professor in the Department of Genetics at Washington University School of Medicine and corresponding author of the current study, takes advantage of high throughput genetic sequencing to examine whole genome data in search of de novo mutations.

"This collaboration started a few years ago, when Donald and I were both working on mutations for the 1000 genomes project," Cartwright says, referring to an ambitious project to produce a comprehensive map of human variation using next-gen sequencing.

The mutations under study may take the form of either point mutations -- individual nucleotide substitutions, or so-called indel (insertion-deletion) mutations. In the latter case, single nucleotides or nucleotide sequences may be either added or subtracted from the genome.

While point mutations and indel mutations can both have adverse affects on health, indels are significantly more difficult to identify and verify. They have a strong potential to cause havoc when they occur in coding portions of the genome as the addition or deletion of nucleotides can disrupt the translation process needed to accurately assemble proteins. (The current study is the first paper to use model-based approaches to detect indel mutations.)

A seemingly simple approach to pinpointing mutations is to compare sequence data from each parent with sequence data from their offspring. Where changes exist at a given site in the offspring, de novo mutations can be inferred and their potential affect on human health, assessed.

In reality, such efforts are complicated by a number of potential sources of error, including insufficient sampling of the genome, mistakes in the gene sequencing process and errors of alignment between sequences. The new method uses a probabilistic algorithm to evaluate the likelihood of mutation at each site in the genome, comparing it with actual sequence data.

Human cells contain two copies of the genome -- one from each parent. For most positions in the genome, the bases from each parent are the same or homozygous but occasionally, they are different or heterozygous.

read more:

Recent DNA studies only scratch the surface of complex Pinoy genetics

DNA—or deoxyribonucleic acid—is not just the double-helical structure that codes genetic traits. It is also the repository of the biological history of a species.

Population-based genetic studies, for instance, have provided evidence that many Filipino groups share a genetic ancestry with the aborigines of Australia, from whom they may have been separated by the Austronesian expansion.

Research using DNA sequences of different individuals also show that Filipinos from over 100 ethno-linguistic groups spread across 18 regions of the Philippines are genetically distant from each other and from people in their regions' city centers.

However, the same data showed scientists that people from city centers, regardless of which region they come from, are genetically close to each other.

The data, acquired from studying parts of our genetic code, only scratches the genetic surface of a very complicated population.

Imagine what secrets we could uncover by sequencing complete sets of DNA.

read more:

Thursday, August 22, 2013

Knocking down the malaria causing parasite

 Targeting the malaria parasite’s ability to make an iron-containing molecule, haem, might help create a vaccine against the disease and also lead to novel drug therapies for blocking infection and transmission, according to research from a team of Indian scientists that was published recently in PLOS Pathogens.

In the course of its complex life cycle, the parasite is able to access haem when it infects red blood cells and gobbles up the haemoglobin those cells contain. Haemoglobin is the molecule that makes it possible for red cells to transport oxygen around the body.

Work carried out two decades back at G. Padmanabhan’s laboratory at the Indian Institute of Science (IISc) in Bangalore had led to the discovery that nevertheless the human malaria parasite could also synthesise haem. The enzymes involved in the complex, multi-step process used by the parasite for doing so were subsequently worked out.

Now, experiments carried out by a team of scientists at the IISc and the National Institute of Malaria Research have shown that having the capability to synthesise haem was “absolutely essential” for the parasite’s development in mosquitoes as well as in early stages of infection when it invades the liver.

When the single-celled parasite consumes haemoglobin found in red cells, the large amounts of haem generated as a consequence is toxic to the organism. It overcomes the problem by turning haem into an insoluble pigment, haemozoin. However, the parasite needs haem for iron-containing proteins, known as cytochromes, that are essential for its own energy production.

“The question arises whether the parasite depends on de novo haem biosynthesis or haem from haemoglobin or a combination of both to make mitochondrial cytochromes,” observed Viswanathan Arun Nagaraj, a Ramanujan Fellow at IISc, and his colleagues in the paper.

To help answer that question, the scientists turned to Plasmodium berghei, a malaria parasite that infects mice. The P. berghei was genetically modified so that two genes for enzymes the parasite required to synthesise haem were knocked out. The scientists were able to show that while much of the haem from haemoglobin breakdown ended up as haemozoin, some of it was also incorporated into the parasite's cytochromes.

Then, through experiments using the human malaria parasite, Plasmodium falciparum, they found that haem synthesised by the parasite while it was in red cells went into cytochromes as well as the haemozoin pigment.

It may be that the ability of synthesise haem was critical to the parasite in situations where it could not get access to the host's haem, such as when an infected individual had sickle cell anaemia, said Prof. Padmanabhan, who is a co-author of the paper.

Clear proof

The scientists found “clear proof ” that haem synthesis was vital for the parasite's development in mosquitoes. Parasites that were unable to make haem did not give rise to its infectious form, known as sporozoites, in the insect’s salivary glands.

Genetically engineered P. berghei, which had one gene for haem synthesis knocked out, could make haem and produce sporozoites when the missing intermediate molecule was supplied. However, those sporozoites, lacking the ability to generate haem, were unable to infect mice.

Knocking out genes for haem synthesis could be a way to produce genetically attenuated sporozoites that might serve as a vaccine candidate for malaria, according to Dr. Nagaraj. Recently published research had shown that attenuated sporozoites could be an extremely effective vaccine against malaria.

What Patients Say Works for Psoriasis

People living with Psoriasis have reported that some of the most effective treatments for their skin include simple interventions like sunlight, salt water, and avoiding stresses.

This is according to a new study by CureTogether, a free resource owned by 23andMe that allows people to share information about their health and treatments.
Psoriasis is one of the most prevalent autoimmune disorders in the United States, affecting an estimated seven million Americans and 125 million worldwide. The condition is characterized by patches of itchy, scaly skin. In its mild form, psoriasis may be just a nuisance, but severe cases can be both painful,  disfiguring and debilitating.
Finding the right treatment can be difficult, so CureTogether asked people living with Psoriasis to rate the effectiveness of 34 different patient-reported treatments.
Participants in the study said they found that phototherapy, cortisone injections, swimming in the ocean, and sunlight were among the most effective, in addition to avoiding stress and triggers and the medications Dovonex and T-Gel. Conversely some common treatments such as oatmeal baths, Epsom salts, and Vitamin D, were among the least effective, according to the study.

Where did this data come from? This is the result of a four-year CureTogether study on Psoriasis, in which 275 people living with the condition shared information about their symptoms and what treatments worked best for them. We’d like to thank those who participated. And just as they shared their experience with treatments, we’re freely and openly sharing the results of the Psoriasis study.
This is part of a regular series of CureTogether research findings. CureTogether’s research findings are different than those made by 23andMe, which look at genetic associations with illness, traits and drug response. But as we continue our work with the CureTogether community, 23andMe hopes to incorporate more of this kind of self-reported information into our own research. CureTogether present its findings just as they are — patient-reported data — to stimulate discussion and generate new insights for further research.
Please tweet, blog, or pass this along to anyone who can benefit or is interested in Psoriasis. Thank you!

Most Effective Rated Treatments for Psoriasis
1. UVB Phototherapy
2. Cortisone injection
3. Salt water/ocean
4. Sunlight
5. Topical corticosteroids
6. Avoid triggers
7. Avoid stress
8. Dovonex
9. UVA Phototherapy
10. T-Gel

 Please read the full article here:

This article is owned and fully credited to 23andme. 

The Battle of the er..bulge..explained

We all know people who can eat whatever they want, not work out, and yet not gain a pound. Meanwhile, eating just one burger, or missing just one cardio session, can weigh much more heavily on others (pun intended).  No doubt many of the differences we observe in weight gain and its relation to food intake and exercise are due to genetics.

Nick Furlotte and Shirley Wu have written a stunning article on why this happens.

They address key questions like:
How do fast food and exercise affect weight on average?
Why you should care if you’re apple or pear
More reason to exercise

Adding genetics to the picture
So how do our genetics influence all of this?   We know that certain genetic factors predispose to obesity while others may protect against it. But a recent study published in PLOS Genetics adds a twist. The researchers showed that a set of 12 genetic factors known to be associated with obesity had less of an effect in people who exercised more and a larger effect in people who did not exercise as often.
We examined the same idea using the data from our customers and found similar results.  In women who do not exercise, the genetic risk factors were associated with weighing 1.4 pounds more than average, while women who exercised weighed only 0.75 pounds more for each risk factor.  In other words, lifestyle may actually influence the effect our DNA has on our weight.
As the size of the weight loss industry attests, weight and obesity are very challenging problems. But with more data, we’ll be able to unravel the relationship between food intake, exercise, genetics, and weight gain even more, hopefully leading to more personalized and effective healthy weight strategies.

You can read their entire article here

Saturday, December 08, 2012

Drag-and-Drop DNA is Novel technique aiding development of new cancer drugs

Using a simple "drag-and-drop" computer interface and DNA self-assembly techniques, researchers have developed a new approach for drug development that could drastically reduce the time required to create and test medications.

In work supported by a National Science Foundation (NSF) Small Business Innovation Research grant, researchers from Parabon® NanoLabs of Reston, Va., recently developed and began evaluating a drug for combating the lethal brain cancer glioblastoma multiforme.

Now, with the support of an NSF Technology Enhancement for Commercial Partnerships (TECP) grant, Parabon has partnered with Janssen Research & Development, LLC, part of the Janssen Pharmaceutical Companies of Johnson & Johnson, to use the technology to create and test the efficacy of a new prostate cancer drug.

"We can now 'print,' molecule by molecule, exactly the compound that we want," says Steven Armentrout, the principal investigator on the NSF grants and co-developer of Parabon's technology. "What differentiates our nanotechnology from others is our ability to rapidly, and precisely, specify the placement of every atom in a compound that we design."

The new technology is called the Parabon Essemblix™ Drug Development Platform, and it combines their computer-aided design (CAD) software called inSçquio™ with nanoscale fabrication technology.

Scientists work within inSçquio™ to design molecular pieces with specific, functional components. The software then optimizes the design using the Parabon Computation Grid, a cloud supercomputing platform that uses proprietary algorithms to search for sets of DNA sequences that can self-assemble those components.

"When designing a therapeutic compound, we combine knowledge of the cell receptors we are targeting or biological pathways we are trying to affect with an understanding of the linking chemistry that defines what is possible to assemble," says Hong Zhong, senior research scientist at Parabon and a collaborator on the grants. "It's a deliberate and methodical engineering process, which is quite different from most other drug development approaches in use today."


Thought you were perfect? Think again!

Nobody Is Perfect: Study Shows People Have 400 Genetic Flaws In DNA

Perfection is something that all humans strive for at one time or another, be it scoring a perfect 100 on a test, making the perfect soufflé, having the perfect play in basketball, or even landing the perfect job. For others, perfection is a state of well-being—as in being perfectly healthy. While achieving perfect health may be plausible in sense of how one feels, new research shows that, at the genetic level, nobody will ever be perfect.

Researchers from the UK have found that, on average, a normal healthy person has no less than 400 potentially damaging DNA variants known to be associated with disease traits. In a study, these researchers also showed that one in 10 people is expected to develop a genetic disease as a result of carrying these variant genes.

Scientists have long known that all people carry some harmful genetic variants, but this is the first time researchers have been able to quantify how many variants each person has on average, and also list them. The study authors said this figure is likely to increase as more powerful genetic studies discover rare genetic variants more efficiently.

While most of these genetic variants are considered “silent” mutations and do not affect health, the team said they can cause problems as they pass down through generations. Some of the more harmful genetic variants found were linked to cancer and heart disease.

Dr. Yali Xue, lead author of the research from Wellcome Trust Sanger Institute at Cambridge, said: “For over half a century, medical geneticists have wanted to establish the magnitude of the damage caused by harmful variants in our genomes. Our study finally brings us closer to understanding the extent of these damaging mutations.”

The evidence comes from the 1,000 Genomes Pilot Project, which has been mapping normal human genetic differences, from tiny changes in DNA to major mutations. The researchers also gleaned data “from the Human Gene Mutation Database (HGMD), a detailed catalogue of human disease-causing mutations that have been reported in scientific literature,” said Xue.

Xue and his colleagues compared the genomes of 179 participants, who were healthy at the time their DNA was sampled, with a database of human mutations compiled at Cardiff University. The research found that along with the 400 average variations, most people also have two DNA changes known to be associated with disease.

“Ordinary people carry disease-causing mutations without them having any obvious effect,” said Dr. Chris Tyler-Smith, a lead researcher on the study from Wellcome. “In a population there will be variants that have consequences for their own health.”

This research gives insight into the “flaws that make us all different, sometimes with different expertise and different abilities, but also different predispositions in diseases,” study coauthor Prof. David Cooper of Cardiff, said in an interview with the BBC’s Helen Briggs.

“Not all human genomes have perfect sequences,” he said in the interview. “The human genome is packed with pervasive, architectural flaws.”

“In the majority of people we found to have a potential disease-causing mutation, the genetic condition is actually quite mild, or would only become apparent in the later decades of life,” Cooper said in a separate statement. “We now know that normal healthy people can possess many damaged or even completely inactivated proteins without any noticeable impact on their health. It is extremely difficult to predict the clinical consequences of a given genetic variant, but databases such as HGMD promise to come into their own as we enter the new era of personalized medicine.”

The work to catalog disease-causing variants has been ongoing for more than two decades, yet the work is still far from complete. Disease variants are extremely rare for the most part and comprehensive searches for such mutations have so far only scratched the surface.

But as DNA sequencing becomes more common in humans, geneticists must determine ethical ways to go about handling sensitive data. For this latest study, researchers anonymized the samples so as not to offer participants any information as to whether or not they may be at risk for a particular genetic disorder.

Tyler-Smith said currently there is no clear answer for what is ethical and what is not when it comes to sharing genetic variation data and potential incidental findings with volunteers in their study.

“All of our genomes contain flaws; some of us will carry deleterious variants but will not be at risk of acquiring the associated disease for one reason or another. For others, there will be health consequences, and early warning could be useful, but might still come as an unwelcome surprise to the participant,” he concluded.This study is published in the American Journal of Human Genetics.


New prenatal genetic test gives parents more answers

New applications of a genetic test could help parents learn more about the genetics of their unborn children.

Three studies released Wednesday in the New England Journal of Medicine highlight the use of microarray testing as the latest technology in chromosome analysis. Researchers suggest using this test to identify potential intellectual disabilities, developmental delays, autism and congenital abnormalities as well as determining why a pregnancy failed.

During pregnancy a number of tests are suggested by the American College of Obstetricians and Gynecologists based on the mother's age, medical history or ethnic or family background, along with results of other tests. Chromosomal microarray analysis is a genetic test that finds small amounts of genetic material that traditional testing such as karyotyping cannot detect.

The genetic material is obtained during a regular amniocentesis (where small amounts of amniotic fluid and cells are taken from the sac surrounding the fetus and tested during the second trimester of pregnancy) or another commonly used test called CVS, or chorionic villus sampling (where a small amount of cells is taken from the placenta during the first trimester).

According to one study, this prenatal testing surpassed standard testing to detect more genetic abnormalities. Lead study author Dr. Ronald Wapner, says with microarray, doctors don't look at chromosomes and are able to evaluate smaller pieces of DNA.

Read the rest of the article here:

We're Gypsies originally from India?

Katherine Harmon  recently published an article that the Romani people—once known as “gypsies” or Roma—have been objects of both curiosity and persecution for centuries. Today, some 11 million Romani, with a variety of cultures, languages and lifestyles, live in Europe—and beyond. But where did they come from?

Earlier studies of their language and cursory analysis of genetic patterns pinpointed India as the group’s place of origin and a later influence of Middle Eastern and Central Asian linguistics. But a new study uses genome-wide sequencing to point to a single group’s departure from northwestern Indian some 1,500 years ago and has also revealed various subsequent population changes as the population spread throughout Europe.

“Understanding the Romani’s genetic legacy is necessary to complete the genetic characterization of Europeans as a whole, with implications for various fields, from human evolution to the health sciences,” said Manfred Kayser, of Erasmus University in Rotterdam and paper co-author, in a prepared statement.

To begin the study, a team of European researchers collected data on some 800,000 genetic variants (single nucleotides polymorphisms) in 152 Romani people from 13 different Romani groups in Europe. The team then contrasted the Romani sequences with those already known for more than 4,500 Europeans as well as samples from the Indian subcontinent, Central Asia and the Middle East.

According to the analysis, the initial founding group of Romani likely departed from what is now the Punjab state in northwestern India close to the year 500 CE. From there, they likely traveled through Central Asia and the Middle East but appear to have mingled only moderately with local populations there. The subsequent doorway to Europe seems to have been the Balkan area—specifically Bulgaria—from which the Romani began dispersing around 1,100 CE.

These travels, however, were not always easy. For example, after the initial group left India, their numbers took a dive, with less than half of the population surviving (some 47 percent, according to the genetic analysis). And once groups of Romani that would go on to settle Western Europe left the Balkan region, they suffered another population bottleneck, losing some 30 percent of their population. The findings were published online December 6 in Current Biology.

The researchers were also able to examine the dynamics of various Romani populations as they established themselves in different parts of Europe. The defined geographic enclaves appear to have remained largely isolated from other populations of European Romani over recent centuries. And the Romani show more evidence of marriage among blood relatives than do Indians or non-Romani Europeans in the analysis.

But the Romani did not always keep to themselves. As they moved through Europe and set up settlements, they invariably met—and paired off with—local Europeans. And some groups, such as the Welsh Romani, show a relatively high rate of bringing locals—and their genetics—into their families.

Local mixing was not constant over the past several centuries—even in the same groups. The genetic history, as told through this genome-wide analysis, reveals different social mores at different times. For example, Romani populations in Romania, Hungary, Slovakia, Bulgaria and Croatia show genetic patterns that suggest a limited pairing with local populations until recently. Whereas Romani populations in Portugal, Spain and Lithuania have genetic sequences that suggest they had previously mixed with local European populations more frequently but have “higher levels of recent genetic isolation from non-Romani Europeans,” the researchers noted in their paper.

The Romani have often been omitted from larger genetic studies, as many populations are still somewhat transient and/or do not participate in formal institutions such as government programs and banking. “They constitute an important fraction of the European population, but their marginalized situation in many countries also seems to have affected their visibility in scientific studies,” said David Comas, of the Institut de Biologia Evolutiva at the Universitat Pompeu Fabra in Spain and co-author of the new paper, in a prepared statement.

Finer genetic analysis of various Romani populations as well as those from the putative founder region of India will help establish more concrete population dynamics and possibly uncover new clues to social and cultural traditions in these groups that have not kept historical written records.