Every DNA counts – and we would know

The National Measurement Laboratory at LGC turned 30 years old this year, and to celebrate we’ve been looking back at notable accomplishments, and looking at where we are now. Clinical measurement is one field where our scientists have excelled and innovated throughout our time.

biology-clinic-doctor-4154Clinical measurement “is the development, use, on-going support, and maintenance of technology for diagnosing, aiding or treating patients.” Modern medicine wouldn’t be possible if we couldn’t rely on the accuracy of clinical tests and diagnosis. Poor measurement can lead to misdiagnosis, incorrect prescription and dosage of medicine, or false interpretation of data. Therefore, reliable certified reference materials are absolutely necessary to ensure the quality and accuracy of clinical measurement.

Throughout the last 30 years, the National Measurement Laboratory (NML) at LGC has worked in this area to ensure that testing methods and reference materials are of the highest quality.

In one case study from 2006¹, scientists in the NML developed isotope dilution liquid chromatography-mass spectrometry (IDMS) methodologies that were then used to generate reference values for clinical reference materials (CRM), some of which led to the analysis of creatine in frozen serum and testosterone in frozen serum CRMs.

In another blog post, we outlined the work we’ve done to improve Alzheimer’s diagnosis, which could lead to techniques for earlier diagnosis of the disease, and in another, we illustrate the importance of harmonising newborn blood sport screening tests to ensure infants are diagnosed and treated early so that they can live as normal lives as possible.

An important part of working in the field of clinical medicine and measurement is communicating our knowledge with other scientists and medical professionals to ensure that good measurement is being performed consistently across the board. We have worked with the NHS and England’s Chief Scientific Officer Sue Hill on doing just that as part of the Knowledge Transfer Partnership Programme, which aims to improve patient care through new approaches to measurement.

And now, our scientists can even count DNA and measure changes to that DNA over time. Identification and targeting of specific genetic sequences forms the basis of many promising advanced healthcare solutions such as: precision (personalised) medicine in cancer, gene therapies to end genetic disorders in children and the detection of pathogenic and non-pathogenic bacteria in a wide spectrum of infectious and autoimmune diseases.

However, the new methods and technologies currently being developed will only achieve their full potential if we can ensure they are safe and can be reproduced. High accuracy reference methods are one of the key factors in supporting their development into routine application.

Using tests for guiding treatment of colorectal cancer as a model, our scienists outlined in a paper published in Clinical Chemistry how a range of dPCR assays and platforms compared and how precisely they measured the cancer mutation. An inter-laboratory study of clinical and National Measurement Institute laboratories demonstrated reproducibility of the selected method. Together these results reveal the unprecedented accuracy of dPCR for copy number concentration of a frequently occurring gene mutation used to decide on drug treatment.

This study has shown that using high-accuracy dPCR measurements can support the traceable standardisation, translation and implementation of molecular diagnostic procedures that will advance precision medicine.

All of this just goes to show you how far we’ve come in 30 years!

¹VAM Bulletin, Issue 35, Autumn 2006, pp 13. ‘Case Study 3: IDMS certification of clinical reference materials using LC-MS/MS”

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.