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:
http://www.sciencedaily.com/releases/2013/08/130825171833.htm

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:
http://www.gmanetwork.com/news/story/323569/scitech/science/recent-dna-studies-only-scratch-the-surface-of-complex-pinoy-genetics
 

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:

http://blog.23andme.com/23andme-research/what-patients-say-works-for-psoriasis/

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