ARK-Genomics - UK centre for farm animal functional genomics

The primary aim of ARK-Genomics is to support the research needs of the Farm Animal Genomics Community. Genomics is a research field in which scientists study the function and role of genes at the whole genome (the collection of genes in a living organism) level. This is particularly timely with the release of the genome sequences of many organisms, including the chicken and soon the cow. The UK Centre for Farm Animal Genomics, ARK-Genomics (http://www.ark-genomics.org), was established with funds from the BBSRC Investigating Gene Function initiative. ARK-Genomics works together with scientists, mostly from research institutes and universities, on research problems. Currently, 55 applications have been successful and 28 are still awaiting a decision from funding bodies. These projects cover a wide range of needs, including the association of genes with physical characteristics (genetic linkage) in specific populations of farm animals and the function of genes, for example, in response to infectious diseases. Genetic linkage studies require the tracking of genes within families, a process known as genotyping. ARK-Genomics has established methods that can track 100s of DNA variants in 1000s of animals. However with the release of the genome sequences of farm animals, millions of DNA variants are being recognised. These differences in DNA sequences between individual or single nucleotide polymorphisms (SNPs) have spawned new technologies for rapid and cheap genotyping of large numbers of SNPs on 1000s of animals. ARK-Genomics provides access to these technologies. Working together with our collaborators we have characterised thousands of genes from chickens, pigs and cattle. These have been used to create DNA chips (DNA specific for each gene spotted onto glass slides) that can be used to detect the expression of genes in any tissue. These arrays will be developed further increasing the representation of genes on the arrays whilst decreasing the costs of their production and use. With the reduction in oligonucleotide (synthetic DNA sequences) prices new arrays based on 20,000 oligonucleotides will be produced. These will reduce the cost of the standard gene arrays by 50 percent. Initially a chicken 20K gene array will be produced in collaboration with a consortium of scientists with interests in development, disease and behaviour. Later similar arrays will be made for cattle, pigs and other farm animals. The details of each array will be matched to the genome databases being created by the ENSEMBL team in Cambridge, the UK home for the human genome sequence. The recent development of methods to manipulate the expression of genes through the application of inhibitory RNAs (siRNA molecules) in cell lines and whole organisms provides a powerful tool to examine the role of genes and their function in the cell. In collaboration with the University of Sheffield ARK-Genomics will provide siRNA specific to over 1000 chicken genes. We expect these will be of immense value to developmental biologists wishing to understand the function of key genes in the development of the chick embryo. These studies will also be aided by the full length copies of the genes (cDNA) available for almost 50 percent of the 18,000 chicken genes. The original development of this genomics facility has created a core of expertise for farm animal genomics and in this application these will be extended. New technologies and resources will be developed, including genomic arrays to compare the genomes of related organisms and the mapping of control regions, sites that determine when and where genes work. This application is for funds to maintain and develop the genomic facilities and resources provided by ARK-Genomics for the needs of the farm animal research community in the most cost effective and timely manner. The establishment of ARK-Genomics has enable d the UK to be at the leading edge of farm animal science, these funds are needed to remain there.

This year farm animals officially entered the genome club with the publication of the draft chicken genome sequence and the initial assembly of the cattle genome released. UK scientists played major roles in these projects and the UK Centre for Functional Genomics in Farm Animals (ARK-Genomics) funded by the BBSRC Investigating Gene Function initiative is playing a central role in providing access to the associated resources. The ARK-Genomics Centre for Functional Genomics in Farm Animals (http://www.ark-genomics.org) established with funds from the BBSRC Investigating Gene Function programme has placed invaluable resources and tools for genomics research at the disposal of scientists working on farm animal species. ARK-Genomics has already provided support for 138 project applications of which 55 have been funded and 28 are awaiting funding decisions. The centre provides access to low cost high throughput genomics tools, such as BAC and cDNA libraries for all the major farm animal species (cattle, pigs and chickens), large scale genotyping of populations, SNP analysis and microarray analysis of gene expression. The resources enable research on animal health and welfare, traits underpinning animal breeding and production and research in which farm animals are used to address fundamental biological questions, especially in vertebrate (chicken) development. ARK-Genomics has the largest collection of farm animal clone resources in the world, with greater than 1.5 million cDNA clones, including the BBSRC collection of 308,000 chicken EST clones, 640,000 cattle clones and 350,000 pig clones. The centre fabricates and uses a range of custom and generic cDNA microarrays with currently up to 15,000 probes. The arrays may be acquired from ARK-Genomics for use in a researchers laboratory, however most collaborators send RNA for microarray analysis within the facility. The RNA is labelled with fluorescent dye and used to interrogate these microarrays, using standard operating procedures, in order to determine the patterns of gene expression, ARK-Genomics will enhance these capabilities by providing facilities for farm animal oligonucleotide arrays and Affymetrix DNA chips. ARK-Genomics provides access to tools for whole genetic mapping with panels of microsatellite markers for chickens, cattle and pigs. From the thousands of single nucleotide polymorphisms (SNPs) identified in farm animal genome sequencing projects genetic markers are being developed for high resolution genetic linkage analysis and association. ARK-Genomics currently uses the ABI SNPlex protocol for the analysis of single SNPs or multiplexed panels of up to 48 SNPs per DNA sample. ARK-Genomics was one of the first groups to provide this facility and has provided expertise to others. ARK-Genomics will extend these capabilities through collaboration with technology providers capable of genotyping 10,000 or more SNPs per DNA sample. ARK-Genomics is also collaborating to provide siRNA probes for 1000 chicken genes, as a tool to examine genes function. In addition tools will be provided for the construction of other siRNA probes, with the long term aim of creating a user supported collection of siRNA probes for all chicken genes. The current proposal includes provision to support the further development of the centre for the UK farm animal research community to provide access to a broader range of genomics tools. These include BAC genomic arrays, ChIP-chip technologies for mapping transcription factor binding sites and methods to map rapidly transcription start sites (CAGE) to complement comparative genomics and other approaches to characterise regulatory regions in the farm animal genome. In conclusion, ARK-Genomics will continue to provide access to genomics and functional genomics resources and technology customised for research on farm animal species. This application is for BBSRC support to underpin the delivery and enhancement of these resources and capabilities.