Purchase of Affymetrix GeneTitan for use in high throughput genotyping

Funds are requested to purchase both a GeneTitan-Multi Channel (GeneTitan) genotyping system and a 5-year warranty.

The application to purchase a GeneTitan has been instigated by Professor Keith Edwards, the academic director of the Bristol Genomics Facility, following discussions with several researchers and industrial partners both at Bristol and beyond.

Researchers who would directly benefit from the placing of a GeneTitan at Bristol include Dr Eric Morgan's Bristol-based research into animal health and livestock production, Dr Amanda Churchill's Bristol-based research into ageing and wellbeing, Professor Ian King's Nottingham-based research into food security, Professor Andy Greenland's research into food security at NIAB, Professor Dr Julie Williams' Cardiff-based research into the disease processes associated with ageing and Dr Peter Jack's wheat breeding at RAGT to address issues associated with food security. All of these cases are in addition to Professor Keith Edwards' own extensive research into wheat breeding and its relationship to food security.

The scientific cases for support all require high throughput/high density genotyping; the GeneTitan enables this on a scale required for genome wide genotyping applications. The GeneTitan achieves this by automating array processing from target hybridization to data generation by combining the required components (hybridization oven, fluidics processing, and state-of-the art imaging device) into a single bench-top instrument. As such the GeneTitan provides the highest throughput and laboratory productivity per operator by minimizing user intervention and allowing unattended, overnight processing of large numbers of samples in parallel. This degree of hands-free automation means that data is consistently reproducible, an essential attribute of gene expression studies in particular, and means that the time typically taken for hands-on array processing is available for data analysis increasing the time to meaningful results for research.

Array technology has recently witnessed exciting developments in terms of both probe content and throughput of samples. For curated genomes, such as human, the wealth of sequencing information has been used to improve 'fixed-content arrays' in which probe sequences are used on a product that can be purchased off-the-shelf with a fixed design. More importantly, a range of non-human genome sequences are now available and this enables custom content arrays to be produced on demand as and when required. To have flexibility in the manufacture process such that a researcher can update the content for an array, is something that is uniquely offered by GeneTitan arrays, enabling a targeted approach such as genotyping across a large number of samples for phenotype/trait studies, such as those involved in plant breeding or population studies.

To make these improvements accessible to all researchers, we are requesting funds to purchase a system with the required flexibility in probe design and high throughput processing as provided by the recently developed 384 sample GeneTitan. This development promises to revolutionise genotyping in a manner similar to that seen for next generation sequencing. This new platform offers a number of benefits over existing systems, for instance the GeneTitan has the capability to process 16-. 24- 96- or 384 samples in parallel, enabling targeted SNP or gene expression analysis to be carried out at medium or high throughout levels, compared with the labour intensive single (eight at most) cartridge array formats that the Bristol Genomics Facility currently houses.

The purchase of the GeneTitan will have a significant impact on many of the users of the Bristol Genomics Facility, specifically on their ability to carry out cost effective high throughput genotyping. As the Facility is open to all users both within and beyond the University (non-Bristol users have included the John Innes Centre, Rothamsted Research, Nottingham University and Aberystwyth University), installation of a GeneTitan will impact on the maximum number of researchers possible and enable research across a wide area of the scientific portfolio of the BBSRC, including wheat, humans and the parasites of sheep.

As the wheat breeding company RAGT has indicated that they will make use of the GeneTitan if it is installed at Bristol, the impact of the purchase will extend beyond the academic environment and hence could have a significant on the ability of UK wheat breeders to develop the next generation of elite wheat varieties having improved agronomic traits such as enhanced disease resistance and/or increased yield.

The Edwards group has an excellent track record of generating science with impact, for instance, it has recently delivered to the wheat breeders a large amount of genomic sequence, and a large number of SNP markers (>7,000 to date), all in a usable form and without any associated IP (via the public database held at CerealsDB). In addition it has, and continues, to work with the genotyping company LGC to develop further molecular markers, which are being used by LGC to provide a service to wheat breeders and academics alike (see LGC web site for further details). The current BBSRC- funded crop club project is developing the SNP resources further and has on its steering committee, all the major wheat breeding companies. In recognition of Prof. Edwards' contribution to UK agriculture the Royal Agricultural Society of England awarded him their 2011 Research Medal, a Medal which acknowledges "research work of outstanding merit, carried out in the United Kingdom, which has proved or is likely to be, of benefit to agriculture".