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Linkage maps for three pig chromosomes, taken from a 1995 paper authored by key participants in the European Commission funded PiGMaP consortium, together with collaborators outside Europe (Archibald et al., 1995).
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DNA sequencing has been characterised by scholars and life scientists as an example of ‘big’, ‘fast’ and ‘automated’ science in biology. This paper argues, however, that these characterisations are a product of a particular interpretation of what sequencing is, what I call ‘thin sequencing’. The ‘thin sequencing’ perspective focuses on the determin...
Context in source publication
Context 1
... mapping allows one to ascertain the relative order of genes (or genomic markers) in linkage groups -i.e. areas of the chromosome whose genes tend to be inherited together (see figure 2). Physical mapping can ascertain the precise positions of genes and genomic markers on chromosomes (see figure 3). ...
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Improvements in DNA sequencing technology and computational methods have led to a substantial increase in the creation of high-quality genome assemblies of many species. To understand the biology of these genomes, annotation of gene features and other functional elements is essential; however for most species, only the reference genome is well-anno...
Citations
... Genome assembly is an iterative process that combines different kinds of data, computational models, and human judgement to represent a genome. For a historical account of the diverse data and ways of reasoning used in the pig genome project, see Lowe [40]. Lowe points out that a genome project was not just about sequencing in the narrow sense of putting DNA base pairs in order, but "thick" sequencing, which also includes the creation of tools, annotation with additional data, and dissemination to a research community that makes reference genomes useful. ...
Background
This paper describes genomics from two perspectives that are in use in animal breeding and genetics: a statistical perspective concentrating on models for estimating breeding values, and a sequence perspective concentrating on the function of DNA molecules.
Main body
This paper reviews the development of genomics in animal breeding and speculates on its future from these two perspectives. From the statistical perspective, genomic data are large sets of markers of ancestry; animal breeding makes use of them while remaining agnostic about their function. From the sequence perspective, genomic data are a source of causative variants; what animal breeding needs is to identify and make use of them.
Conclusion
The statistical perspective, in the form of genomic selection, is the more applicable in contemporary breeding. Animal genomics researchers using from the sequence perspective are still working towards this the isolation of causative variants, equipped with new technologies but continuing a decades-long line of research.
... On the iterative, back-and-forth relationship between DNA mapping and sequencing, seeLowe (2018). In this book, we assess different ways of operationalising these mappingsequencing relationships and their underlying power dynamics. ...
In this chapter, we focus on an institution that represents the exclusivity of the International Human Genome Sequencing Consortium (IHGSC) while also contributing to the ‘funnelling effect’ that shaped it: the Sanger Institute. After situating its origins in the sequencing of the worm Caenorhabditis elegans , we portray the Sanger Institute as a driver in the formation of the IHGSC and as an advocate for the concentration of its membership into a few high-throughput sequencing centres. The intensification of this genome centre model, alongside competition with the corporate sequencing effort led by Celera Genomics, shaped the formation of the IHGSC. As a result, the large-scale production of sequence data became an increasingly differentiated and exclusive practice undertaken by its members. Conversely, the smaller laboratories that used this data in their own genetics research were sidelined from the determination of the human reference sequence.
... Pig protein and RNA sequence data were obtained from specific databases, and data on pig cDNA and ESTs were also downloaded from GenBank. Many of the cDNAs and ESTs had been generated by the Animal Genome Research Program at the National Institute of Agrobiological Sciences in Japan, and the Japan Institute of Association for Techno-innovation in Agriculture, Forestry and Fisheries (Groenen et al., 2012 and Supplementary Information;Lowe, 2018). These resources were generated in part using samples from cloned offspring of TJ Tabasco (Schook et al., 2005;Uenishi et al., 2012). ...
... It meshed with the more significant role that manual procedures had in the annotation of the S. scrofa reference genome. The combination of the automated pipeline with the bespoke manual sequencing distributed in laboratories across the world constituted a combination of Stein's factory and cottage industry models, and was therefore different to the case of Ensembl discussed above (Lowe, 2018). 30 This initial curation created a visualisation that displayed the sequence data along with another layer of information indicating evidence for the possible presence of genes. ...
Through examining how the reference genomes of yeast, human and pig were annotated, in this chapter we further identify how the involvement or non-involvement of particular communities in the creation of a reference genome can affect the nature of the product. We therefore continue to distinguish the qualities of separate reference genomes, which are otherwise rendered as commensurate and equivalent objects by data repositories such as RefSeq. In doing so, we present alternative historical trajectories to the narrative centred around the Human Genome Project. In particular, this chapter conveys how the relationship between pig genomicists and a key annotation group at the Sanger Institute shaped the direction of annotation at that institution. This led the Sanger Institute group to formulate a new way of conducting ‘community annotation’, an approach that had previously been performed in a limited and attenuated fashion, for example at the jamboree meetings of Celera Genomics.
... Individual researchers and laboratories, as well as the community as a whole, pursued a variety of different avenues of potential support and funding. This drew upon strategies of diversification and enabled different pots of funding to be accessed for particular tasks that could contribute towards the wider effort of sequencing the genome (Lowe, 2018). Like the IHGSC, the SGSC was supported by national public funding agencies-among them the USDA, the UK's Biotechnology and Biological Sciences Research Council (BBSRC) and the Danish Government-but also sub-national administrations, such as funders from specific US states, as well as industry bodies. ...
... The funds from the USDA were complemented by additional resources provided by Iowa State University and North Carolina State University, as well as industry bodies: the National Pork Board, the Iowa Pork Producers Association and the North Carolina Pork Council. The other institutions involved in the SGSC brought their own resources to bear on the overall programme, once again drawing on grants to perform particular pieces of research and create new resources (Lowe, 2018). 27 Key to the USDA's support was the demonstration that the community of pig genomicists was united behind one project and that the initiative had international buy-in. ...
... Photographs courtesy of Lawrence Schook the Sanger Institute. This reference sequence and the physical map were largely derived from the CHORI-242 library that de Jong had produced for Schook, alongside the fosmid library from TJ Tabasco and the three other BAC libraries mentioned, produced by CEA-INRA, the Roslin Institute, and de Jong's group at USDA MARC's request (Schook et al., 2005;Humphray et al., 2007;Lowe, 2018). Annotation of the reference sequence made use of the cDNA libraries derived from the cultures of TJ Tabasco's clones (Fig. 5.4). ...
This chapter introduces the story of pig genome mapping and sequencing. It presents the heterogeneous interests and activities of a small and tight-knit community, in which maps, sequencing data, resources and tools were developed for—and immediately linked to—the problems of pig breeding and transplantation biology. A community of pig genomicists converged in mapping projects that took place from the early-1990s onwards. In these initiatives, they characterised the positions of genes and genetic markers on chromosomes with a view to this information being deployed in agriculture and biomedicine. This community was intimately involved in most aspects of the creation of a reference genome, either directly or by guiding the focus of the Sanger Institute, the institution that was contracted to undertake the sequence determination. The Sanger Institute therefore had a different role in pig genomics than in yeast and human genomics. This distinct role was deeply conditioned by the historical trajectory of the pig genetics community.
... The first porcine genome mapping initiative funded by the EC was PiGMaP (1991)(1992)(1993)(1994)(1995)(1996). The aim of PiGMaP was to populate maps of pig chromosomes with various kinds of genetic markers, and to develop molecular, statistical and informatics tools to be able to more densely populate these maps and then to identify areas of the genome associated with variation in measurable traits (Lowe, 2018). Chris Warkup (interview data) suggested that for breeding companies, joining in with PiGMaP was "the cost of staying in business … You will go out of business if you do not invest in the latest technology". ...
This paper presents a longitudinal case study in UK biotechnology covering some 30 years during which genomic technologies were introduced into pig breeding. This case study demonstrates how co-innovation involving existing small and medium sized enterprises, together with contributions from academics, has enabled companies to obtain the resources needed for value creation. Important contributions at critical junctures from public funding, pivotal contributions of individuals, and entry of new enterprises supplying essential resources, have enabled the fruitful realisation of new value creation. This paper contributes to the literature by taking a historical perspective, demonstrating how enabling long-term networking relationships including relevant academics, research institutions, funders and knowledge brokers has the potential to generate an innovation ecosystem that can respond effectively to a range of external challenges and take advantage of new techno-scientific opportunities.
... Pigs are phylogenetically more distant to humans than nonhuman primates are, but are more abundantly available, are prolific, their breeding can be controlled, and as a farm animal they are deemed to be a more acceptable subject of this kind of research by many more people. 21 20 Other significant pig genomics groups have also been explored in the literature (Lowe, 2018(Lowe, , 2021Lowe et al., 2022). Other researchers have been far more involved in the practical aspects of xenotransplantation research, such as David Cooper, David Sachs and Angelika Schnieke. ...
Biologists who work on the pig ( Sus scrofa ) take advantage of its similarity to humans by constructing the inferential and material means to traffic data, information and knowledge across the species barrier. Their research has been funded due to its perceived value for agriculture and medicine. Improving selective breeding practices, for instance, has been a driver of genomics research. The pig is also an animal model for biomedical research and practice, and is proposed as a source of organs for cross-species transplantation: xenotransplantation. Genomics research has informed transplantation biology, which has itself motivated developments in genomics. Both have generated models of correspondences between the genomes of pigs and humans. Concerning genomics, I detail how researchers traverse species boundaries to develop representations of the pig genome, alongside ensuring that such representations are sufficiently porcine. In transplantation biology, the representations of the genomes of humans and pigs are used to detect and investigate immunologically-pertinent differences between the two species. These key differences can then be removed, to ‘humanise’ donor pigs so that they can become a safe and effective source of organs. In both of these endeavours, there is a tension between practices that ‘humanise’ the pig (or representations thereof) through using resources from human genomics, and the need to ‘dehumanise’ the pig to maintain distinctions for legal, ethical and scientific reasons. This paper assesses the ways in which this tension has been managed, observing the differences between its realisations across comparative pig genomics and transplantation biology, and considering the consequences of this.
... Once the initial stages of assembly were conducted at the Sanger Institute and the Genome Analysis Centre in nearby Norfolk, further assembly was performed at Roslin by Archibald, and Roslin scientists also contributed towards the genome annotation. 63 In 2017, a new high-quality version of the swine reference genome was published. This project was led by Archibald and Tim Smith of the USDA Meat Animal Research Centerand significant portions of the work took place at Roslin. ...
From the 1980s onwards, the Roslin Institute and its predecessor organizations faced budget cuts, organizational upheaval and considerable insecurity. Over the next few decades, it was transformed by the introduction of molecular biology and transgenic research, but remained a hub of animal geneticists conducting research aimed at the livestock-breeding industry. This paper explores how these animal geneticists embraced genomics in response to the many-faceted precarity that the Roslin Institute faced, establishing it as a global centre for pig genomics research through forging and leading the Pig Gene Mapping Project (PiGMaP); developing and hosting resources, such as a database for genetic linkage data; and producing associated statistical and software tools to analyse the data. The Roslin Institute leveraged these resources to play a key role in further international collaborations as a hedge against precarity. This adoption of genomics was strategically useful, as it took advantage of policy shifts at the national and European levels towards funding research with biotechnological potential. As genomics constitutes a set of infrastructures and resources with manifold uses, the development of capabilities in this domain also helped Roslin to diversify as a response to precarity.
... Genomic data are among the best standardised and most valued data types available to precision medicine. Yet they require complex intermediations to be used as medical evidence (Rheinberger 2010), including curation and visualisation practices that make it possible for these data to move across user communities (Lowe 2018). This considerably complicates the interpretation of genomic sequences (Huang et al., 2016). ...
Huge amounts of genomic data produced by researchers around the world undermine data-centred discovery and therapeutic development. This paper considers how researchers make decisions about the actionability of specific datasets and the conditions that allow such data to be trusted. We discuss the case of COSMIC, a leading cancer genomics database which aggregates a large amount of sources. We research what the actionability of cancer data means in different situations of use, contrasting exploratory and diagnostics research. They highlight different questions and concerns upon genomic data use in medical research. At the same time, strategies and justifications pursued to evaluate and re-use can also share important similarities. To explain differences and similarities, we argue for an understanding of actionability and trust in data that depends on the goals and resources within the situation of inquiry, at the same time as the social epistemology of standards.
In this paper, rather than focusing on genes as an organising concept around which historical considerations of theory and practice in genetics are elucidated, we place genetic markers at the heart of our analysis. This reflects their central role in the subject of our account, livestock genetics concerning the domesticated pig, Sus scrofa. We define a genetic marker as a (usually material) element existing in different forms in the genome, that can be identified and mapped using a variety (and often combination) of quantitative, classical and molecular genetic techniques. The conjugation of pig genome researchers around the common object of the marker from the early-1990s allowed the distinctive theories and approaches of quantitative and molecular genetics concerning the size and distribution of gene effects to align (but never fully integrate) in projects to populate genome maps. Critical to this was the nature of markers as ontologically inert, internally heterogeneous and relational. Though genes as an organising and categorising principle remained important, the particular concatenation of limitations, opportunities, and intended research goals of the pig genetics community, meant that a progressively stronger focus on the identification and mapping of markers rather than genes per se became a hallmark of the community. We therefore detail a different way of doing genetics to more gene-centred accounts. By doing so, we reveal the presence of practices, concepts and communities that would otherwise be hidden.
