How genotyping is aiding in the fight against malaria

mosquitoe-1548975_19203.2 billion people across 106 countries and territories, live in areas at risk of malaria transmission. The serious and sometime fatal mosquito-borne disease is caused by the Plasmodium parasite – in 2015, malaria caused 212 million clinical episodes, and 429,000 deaths.

Malaria has been a public health problem in Brazil ever since it was brought to the region during its colonization. By the 1940s it is estimated that six to eight million infections and 80,000 malaria-related deaths occurred every year in the country.

Due to a concerted series of malaria control policies, Brazil has recorded a 76.8% decrease in malaria incidence between 2000 and 2014 – and effort which the country was praised by the WHO.  In 2014, there were 143,910 of microscopically confirmed cases of malaria and 41 malaria-related deaths.

Part of Brazil’s malaria control policy involves the use of primaquine – a medication first made in 1946, to treat and prevent malaria. It is particularly effective against the Plasmodium vivax parasite that is prevalent in the Brazil.

Unfortunately primaquine can induce haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals and may lead to severe and fatal complications. 330 million people worldwide are affected with G6PD deficiency, with recent studies suggesting the prevalence of the deficiency could be as high as 10% in Brazil.

Recently, molecular biologists from LGC enabled a cutting edge study in collaboration with researchers from Brazil and the London School of Hygiene and Tropical Medicine.

The researchers looked for mutations in a sample of 516 male volunteers that could be used as clinical indicators for G6PD deficiency that could lead to complications in people prescribed with primaquine.

Blood samples were collected from around Brazil at hospitals during surgeries, as well as using the local Brazilian radio stations to ask people to come and submit blood.

Needing a fast and efficient way to generate results in high throughput, the team turned to LGC’s integrated genomics toolkit to facillitate the research. Each sample was screened against 24 KASP assays to assess the genetic bases of G6PD deficiency. In combination with the IntelliQube®,a fully automated point and click PCR system;  the team collected the data in roughly three hours of instrument time and one hour hands on time.

KASP is a flexible, highly specific genotyping technology, which can be used to determine SNPs and InDels.  KASP uses unlabelled oligonucleotide primers, which gives the technology a cost advantage and allows more data to be generated, increasing data quality.

The data indicates that approximately one in 23 males from the Alto do Juruá could be G6PD deficient and at risk of haemolytic anaemia if treated with primaquine. The authors conclude that routine G6PDd screening to personalize primaquine administration should be considered – particularly as complete treatment of patients with vivax malaria using chloroquine and primaquine, is crucial for malaria elimination.

The teams are continuing their collaboration to help further research in to treatments for malaria, and we can’t wait to see more!

To access the paper, please click here, or to see the IntelliQube in action and learn more about this automated PCR instrument click here.

 

 

Sources:

Malaria. (2017, July 13). Retrieved August 8, 2017, from https://www.cdc.gov/malaria/about/index.html

Maia, U. M., Batista, D. C., Pereira, W. O., & Fernandes, Thales Allyrio Araújo de Medeiros. (n.d.). Prevalence of glucose-6-phosphate dehydrogenase deficiency in blood donors of Mossoró, Rio Grande do Norte. Retrieved August 8, 2017, from http://www.scielo.br/scielo.php?pid=S1516-84842010000500017&script=sci_arttext&tlng=en

 

This blog post was originally published on the Biosearch Technologies blog.

Accelerating rice improvement in South Asia

WP_20180515_009Diversity is the spice of life and is also key to breeding rice that delivers increased yields. Rice is a crucial staple food for about half a billion people in Asia, but it suffers from diseases that reduce yields, destroy harvests and put food security and livelihoods at risk. But there is hope – by tracking DNA markers of natural genetic variants through generations of crosses, breeders can identify better combinations that enrich crop vitality and resilience leading to more reliable and sustainable rice production.

collaborative project between Bangor University and LGC with a university partner in India (SKUAST), a research institute in Pakistan (NIBGE) and, in Nepal, a government research centre (NARC) and a private seed company (Anamolbiou) is addressing this challenge and has already identified over a million new markers in rice. They can reveal linkage to genes and patterns of diversity that help rice breeders select for a wide range of resistance genes to improve many different varieties. The project continues to develop these markers into more KASP assays that will be made available in publicly searchable databases.

Modern disease-resistant varieties are not always well adapted to specific environments, so breeders aim to incorporate markers for both biotic and abiotic stress resistance as well as yield components into locally accepted varieties that may already possess value traits, such as aroma. Molecular markers such as Simple Sequence Repeats (SSRs) in rice were developed in the 1990s for marker-assisted selection (MAS) and these are still used by some rice breeders in Asia to improve selection efficiency. Smaller breeding companies do not have all the resources (i.e. trained personnel, instrumentation for extraction or genotyping) to use such markers in-house. They can benefit from a service-based approach such as LGC Genomics’ genotyping service using KASP technology that offers a lower cost per data point and is faster to implement or use in their own lab. KASP assays offer greater sensitivity, speed, and safety than the older techniques, such as SSRs, when carried out in breeders’ own labs.

WP_20180515_007The collaboration with Bangor University and partners has already developed new methods to identify suitable SNP and InDel markers that can replace existing SSRs in target breeding crosses which have been adopted by Nepalese breeders. Now, a broader survey of suitable SNPs and InDel markers, across a set of 130 publically available rice genome sequences selected for geographic diversity, is discovering novel markers that are relevant to both Indica and Japonica rice backgrounds.

Before the research team started this project there was a choice of 2055 useful KASP assays that breeders could use, depending on their breeding strategy, but this project has increased the choice to over 245,000 potential markers that should benefit a wider range of rice breeding programs. This increase in the number of KASP assays enables the project and research community to utilize KASP technology on a scale that was only available to big breeding companies before this project. It’s exciting times for rice breeding!

Bangor University and partners plan to make thousands of the rice markers from this project available in the form of a searchable database so that rice breeders can easily find the most suitable options to replace their target SSRs in existing programs or to identify the appropriate loci for a range of possible new crosses. LGC will also offer them as validated KASP assays on its website. The large database of validated KASP assays produced by this project will thus give rice breeders the ability to carry out genomic selection (GS) with many thousands of loci across their populations, enabling smaller breeders to benefit from the same genomic scale technologies that generally require significant resource investment to develop on their own. The availability of this marker set to the public sector, and the services provided by LGC Genomics, will enable rice breeders of all sizes to apply genomic tools to accelerate their MAS and GS breeding programs to develop new rice varieties that will improve food security.

To learn more about our KASP genotyping services click here.

 

This blog originally appeared on the Biosearch Technologies blog.

Revolutionising cancer treatment one Array at a time

While the science of pharmacogenomics has been around for years, its popularity is starting to pick up steam as precision medicine and how we treat individual patients becomes more and more common place in the medical world. Geneticists and doctors are fully embracing the fact that our individual genes make us all unique and that these genes hold clues to how each patient’s body will metabolise medications.

Pharmacogenetics, or the study of how people respond differently to medicines due to their genetics, is making a splash lately thanks to companies like Minneapolis, MN-based OneOme, which co-developed its RightMed test with Mayo Clinic. The company collects a patient’s DNA sample using a simple cheek swab that is then analysed at OneOme’s lab with PCR – in this case on LGC’s IntelliQube® – to determine the patient’s genetics.  This information is then used to determine whether the patient has any genetic variations that may cause them to have a certain reaction to a medication. These results give doctors “graphic genetic pinpoint accuracy” on the medications that should work and those likely to be less effective. In simplest terms, these tests, combined with PCR instruments are empowering patients and doctors with information that may not only make their lives better, but also safer. Or as we like to say, science for a safer world.

Take a look at just how much pharmacogenomics is impacting and “revolutionizing” patient care by watching the video here, or visit our website.

 

This story was originally published on the Biosearch Technologies blog.

Our top 5 favourite scientific breakthroughs in history

British Science Week kicked off on the 9th March and this year’s theme is ‘Exploration & Discovery’, which encompasses the spirit of scientific enquiry. The week is a ten day celebration of science, technology, engineering and maths.

As humans, we love to celebrate big moments in history and retell stories that help us understand our own story. Famous thinkers often become legends who attain ‘larger than life’ status. But it’s important to remember that our heroes of science pursued science every day and dedicated themselves to their work. Innovations are often accomplished over the course of lifetimes with the help of many scientists.

We are constantly building on the knowledge of the past to take science into the future, and it’s exciting to think that we could each play a part in something big. After all, there are often just a few steps between ‘business as usual’ and ‘making history’. So keep up the good work!

To celebrate the spirit of exploration and discovery, here’s a look at our top five favourite scientific breakthroughs:

Genomics/DNA: While the term ‘genomics’ was only coined in 1986, by geneticist Tom Roderick, the actual study of the human genome is more extensive than that. A genome is defined as all the genetic information of an organism, and therefore genomics, the study of the complete genetic material of these organisms.

Gregor Mendel

Selective breeding has been practiced for thousands of years, but it wasn’t until the Augustinian friar Gregor Mendel undertook his studies in the mid-19th century that modern genetics as we know it was born. Do you remember practicing Mendel’s laws in school, determining traits in offspring based on dominant and recessive traits? It was the most fun to be had in biology.

Later, British Nobel Prize-winners James D. Watson and Francis Crick published the discovery of the helical structure of DNA, based on work done by Rosalind Franklin and Raymond Gosling, and then molecular biologists began to sequence nucleic acids. By 2001, the Human Genome Project completed a rough draft of the human genome, a feat which is being replicated with the 1000 Genomes Project. Now, scientists are using genomics to forge the way forward in personalised medicine, conservation, synthetic biology and gene editing. This all within the relatively short space of 150 years!

Domestication of plants & fermentation: Perhaps not a ‘discovery’, the domestication of plants definitely changed the course of human history, allowing populations to settle and grow. Plant domestication first occurred about 10,000 years ago in the Middle East. This change from hunter-gatherer societies to agricultural societies is largely seen as the beginning of the rise of civilisation.

Often, crops would go bad before they could be consumed, so in order to make the yields last longer and feed more, humans began to use a chemical process called fermentation in the Neolithic Age. This process converts sugars and carbohydrates to acids, gases or alcohol, and it was used to preserve food and beverages. Some of our favourite food and drinks were invented thanks to fermentation, including beer, wine, yoghurt, kimchi and sauerkraut (not that this is the only reason it made the list).

Alexander Fleming in his St Mary’s lab in London

Penicillin/antibiotics: Discovered in 1928 by Scottish scientist Alexander Fleming, penicillin became the world’s first true antibiotic. By the time Fleming made this discovery, scientists had reported the antibacterial properties of some moulds, including penicillium. But they were unable to successfully harness these properties. For his part, Fleming recounted that his historically famous discovery was a lucky accident. After mistakenly leaving a Petri dish containing Staphylococci exposed in his lab, he returned from holiday and noticed it had grown a blue-green mould. The mould slowed the growth of the bacteria around it, and after studying this effect, Fleming was able to use his ‘mould juice’ (blegh) to kill a range of harmful bacteria.

Ultimately, this discovery has greatly reduced the number of deaths from infection, playing an enormous role in improving the mortality rates around the globe. Today, antimicrobial resistance is a growing concern, and medical professionals warn that if we do not discover new classes of antibiotics, infections could kill as many as ten million people a year by 2050. But scientists are looking for new antibiotics in unexpected places, like toilet seats, dog food bowls, and even laptop keyboards.

Steam engine: Another British invention, the steam engine is not so much a scientific breakthrough as it is a series of breakthroughs over the course of one hundred years, and it certainly changed the course of human history. This invention has roots in Roman times, but it wasn’t until the 17th century when Englishman Thomas Savery developed a model of the steam engine that it became a promising innovation. Soon after, another Englishman, Thomas Newcomen, and Scottish engineer James Watt made the design more efficient and the rest, as they say, was history.

James Watt’s steam engine at the Thinktank museum in Birmingham (© Copyright Ashley Dace)

Connected to a piston and cylinder, a boiler filled with water is heated until the water turns to steam. Once the steam expands, it travels through the cylinder and moves the piston first forward, and then, once the steam is cooled, backward. This back-and-forth process, attached to a larger machine, moves the machine forward, in what must be one of the most rudimentary explanations ever of this amazing process. This engine was adapted for use in boats, cars, and, of course, trains. The idea that people began to cross continents in record time just by turning a liquid into a gas over and over is pretty bonkers when you think about it.

Periodic table: This one may be last on our list, but it’s definitely not last in our hearts. Chemists have spent a lot of time throughout history on the classification of chemical elements, but when Russian chemistry professor Dmitri Mendeleev got hold of it, things changed. He published his version in 1869, much to the chagrin of German chemist Julius Lothar Meyer, who published his version just one year later in 1870 and probably thought we’d all be talking about “Meyer’s Table” right now.

Like others before him, Mendeleev saw when elements were listed in order of atomic weight, elements at certain intervals shared physical and chemical properties. But Mendeleev left gaps in the table, predicting where an element hadn’t yet been discovered and it’s properties. He also took care to classify elements into ‘chemical families’. And just like any good developer, he released an updated version in 1871. Adjustments have been made from time to time, when new elements have been discovered or to make the table more easily readable, but Mendeleev is still considered the Father of the Periodic Table.

What are your favourite breakthroughs?

Science for a safer world

In the twenty-first century, science has been brought to the forefront, informing all aspects of our lives. In order for it to make our world safer, it’s especially important for science to remain steadfast, reliable and responsible. Science should not have an agenda; science is the agenda. It should not be informed by policy or opinion, but should inform policy and opinion. And at LGC, we work to ensure that our science does just that.

From our origins testing tobacco, alcohol and food products for adulteration in the 19th century, LGC has built a commitment to using science for a safer world.

This commitment underpins all of what we do. From testing drinking water and the quality of food to researching medicines and diagnostics, we work to ensure both our customers and the public benefit from our knowledge. Our scientists develop accurate methods for detecting infectious and congenital diseases and we test more than 6,000 products and supplements for banned substances, certifying that they are safe for athletes at all levels to use.  In our role as UK designated National Measurement Institute for chemical and bio-measurement, we solve measurement challenges in diagnostics, food safety, cancer research and environmental testing. At the heart of everything we do is the question, How can we make the world safer?

LGC is also looking to the future, to advance research, technologies, solutions and medicines that will build a better, more secure future.

Now, through this blog, we hope to bring our science to you, shedding light on the vital work we do every day.

What does ‘Science for a safer world’ mean to you?