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Transcript map of the human genome by radiation hybrid mapping of expressed sequence tags (ESTs)

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Identification of genes has until recently been pursued on a case by case basis, using either biochemical and protein identification methods or positional cloning genetic techniques. The advent of large scale cDNA sequencing projects in the past few years is likely to lead to the identification of the majority of human genes in the near future. The exploitation of this huge amount of information will, however, require a means to integrate the genes into existing maps including genetic maps and physical maps.

This project is part of a collaborative project whose overall objectives are to create a high resolution, fully integrated map of the human genome. In particular this project concerns a world wide effort to map the estimated 60,000 to 70,000 genes in the human genome. The method chosen by this consortium is whole-genome radiation hybrid mapping (WG-RHM) of at least 100,000 expressed sequence tags (ESTs) of which approximately 10,000 are currently in public databases and the rest are to be generated by a separately initiated public-domain cDNA sequencing project (Merck/St Louis). The consortium members have already embarked upon the project using individually initiated means of funding a significant part of the costs associated with the work, drawing upon their experience and infrastructure for performing large scale genomic projects. The present application is to request funding for three significant aspects of the project that are best done in a co-ordinated fashion, or for which economies of scale and sharing of resources can be done: (1) Maintain databases for the EST sequences and associated information; (2) Fund the synthesis of PCR primers for approximately 30 % of the ESTs: (a) automated design of PCR primer pairs for non-redundant set of ESTs, (b) commercial synthesis, aliquoting and distribution to collaborators; (3) Centralized database of RH mapping results, map-construction and co-ordination of mapping information with the physical mapping group.

The single largest cost of a transcript mapping project is the synthetic oligonucleotides. No single laboratory or country could afford to carry the cost for the whole project. Furthermore, the same primers will inevitably used by many different laboratories carrying out different aspects of the project. Since the requirement in terms of quantity of primer of any one laboratory is quite modest, and even the smallest synthesis of oligonucleotide provides sufficient for thousands of PCR reactions the centralization and sharing of this resource is compelling if not obligatory. It is also intended that the company or companies chosen for this project will make the same primers available at reasonable cost as a catalogue item thus allowing access by even small laboratories and facilitating full exploitation of the results of the WG-RH map.

The construction of the transcript map by radiation hybrid mapping is wholly feasible within the timespan proposed and will result in high resolution maps integrating expressed sequences and genetic markers and other STSs. This will aid the construction of the physical map which initially will be based on YACs and this program will be co-ordinated closely with the European physical mapping group (Biomed2 application: EuroYAC, co-ordinator Dr Nigel Spurr). Two of the partners are currently constructing RH framework maps based on polymorphic microsatellite genetic markers (AFM and CHLC markers). The benefits of integrating these genetic markers with the gene map will be realized immediately in gene-cloning projects, especially for monogenic diseases; however in the longer term there will be even greater impact on the more common,economically important multifactorial diseases due to the greater reliance on a candidate gene approach.

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CSC - Cost-sharing contracts

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THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
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Roosevelt Drive
OX3 7BN OXFORD/HEADINGTON
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Letzte Aktualisierung: 1 April 1996

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Permalink: https://cordis.europa.eu/project/id/BMH4951565/de

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