The International RH Mapping Consortium

For this article, Jennifer Fisher Wilson interviewed Panagiotis Deloukas, senior group leader at the department of human genetics at Sanger Centre Wellcome Trust Genome Campus in Cambridge, England. Data from the Web of Science (ISI, Philadelphia) show that the Hot Papers are cited 50 to 100 times more often than the average paper of the same type and age. P. Deloukas, G.D. Schuler, G. Gyapay, E.M. Beasley, C. Soderlund, P. Rodriguez-Tome, L. Hui, T.C. Matise, K.B. McKusick, J.S. Beckmann, S. Bentolila, M.T. Bihoreau, B.B. Birren, J. Browne, A. Butler, A.B. Castle, N. Chiannilkulchai, C. Clee, P.J.R. Day, A. Dehejia, T. Dibling, N. Drouot, S. Duprat, C. Fizames, S. Fox, S. Gelling, L. Green, P. Harrison, R. Hocking, E. Holloway, S. Hunt, S. Keil, P. Lijnzaad, C. Louis-Dit-Sully, J. Ma, A. Mendis, J. Miller, J. Morissette, D. Muselet, H.C. Nusbaum, A. Peck, S. Rozen, D. Simon, D.K. Slonim, R. Staples, L.D. Stein, E.A. Stewart, M.A. Suchard, T. Thangarajah, N. Vega-Czarny, C. Webber, X. Wu, J. Hudson, C. Auffray, N. Nomura, J.M. Sikela, M.H. Polymeropoulos, M.R. James, E.S. Lander, T.J. Hudson, R.M. Myers, D.R. Cox, J. Weissenbach, M.S. Boguski, D.R. Bentley, "A physical map of 30,000 human genes," Science, 282:744-6, Oct. 23, 1998. (Cited in more than 190 papers since publication) In 1994, an international group of scientists formed a consortium to construct a human gene map in which cDNA-based sequence-tagged site (STS) markers would be physically mapped and then integrated with the genetic map of polymorphic microsatellite markers. The group, the International RH Mapping Consortium, organized soon after the controversial debate regarding whether the gene map should be constructed in the public or the private domain. According to Panagiotis Deloukas, senior group leader at the department of human genetics at Sanger Centre Wellcome Trust Genome Campus in Cambridge, England, the announcement that Merck Sharp & Dohme (U.K. subsidiary of Merck & Co., Whitehouse Station, N.J.) was going to fund a large-scale expressed sequence tag (EST) project, with all data to be made freely available in the public domain, stimulated the first round of informal discussions. Plans to form the consortium were announced shortly thereafter. "The availability of ESTs and the recognition that radiation hybrid (RH) mapping could be applied to the whole genome to position genes and other features relative to genetic [maps and] markers, united groups working in the United States, Europe, and later Japan to undertake this project," Deloukas says. Participants in the International RH Mapping Consortium included the University of Cambridge; the European Bioinformatics Institute (EBI) in Hinxton, U.K.; Genethon Human Research Center in Evry, France; Merck & Co.; the National Center for Biotechnology Information (NCBI) in Bethesda, Md.; Wellcome Trust Centre for Human Genetics at the University of Oxford; the Sanger Centre in Hinxton, U.K.; Stanford Human Genome Center, Palo Alto, Calif.; Washington University Genome Sequencing Center, St. Louis; the Center for Genome Research at the Whitehead Institute for Biomedical Research, Cambridge, Mass.; and Kazusa DNA Research Institute in Chiba, Japan. Consortium members agreed to construct the map of the 60,000 to 70,000 human genes and make the map available in the public domain, with the aim of aiding scientific research all over the world. Four years later, in this paper, the group published a map of 30,181 human gene-based markers--approximately half of the total estimated number of human genes. The publication of the map represented a significant breakthrough in human genome mapping: It had twice as many genes as the group's previous release1 and included most of the genes that encode proteins of known function (4,684 of the 6,000 human genes of known function). It also improved the accuracy of the mapping. Known as GeneMap 98, it was generated by means of whole genome RH mapping, which positions ESTs relative to other informative markers such as microsatellites. A set of approximately 1,100 genetic markers from the Genethon genetic map was used to construct the framework maps and to form the basis for map integration. "This was the first-ever substantial chart of human genes, reflecting a major breakthrough from a few thousand to 16,000 to 30,000 in just three years," Deloukas says. The publication has been cited frequently because, he suggests, a tool that provides information on the location of more than 30,000 genes is of interest to a wide range of research projects. The map is accessible free to the public on the NCBI's Web site (www.ncbi.nlm.nih.gov). The Web display of the map provides integration with other biological data. Various members of the consortium contributed the markers that make up the map. The Sanger Centre, Whitehead Institute, and Genethon contributed three-quarters of the total number. In all, the 41,664 cDNA-based STS markers identified represented the 30,181 human genes included in the map. Individual members of the consortium contributed to the project in other ways. "The calculation of the map was undertaken by the Sanger and Stanford groups with assistance from the Whitehead group, which has played a major role in the calculation of the 1996 map release, and the NCBI and EBI groups. The NCBI group has assisted the mapping groups throughout the project with the distribution of the UniGene set and has [constructed and maintained] the Web site. The group at EBI has been responsible for creating and maintaining a public repository of all mapping data. And both the Sanger and Stanford groups have created radiation hybrid mapping servers to allow researchers to map a marker relative to the gene map," Deloukas says. Since the 1998 Science publication, the consortium has produced an electronic update of the map, GeneMap 99, which is available through the map display at NCBI. The 1999 release maps an additional 7,408 gene-based markers representing 5,603 genes. The RH mapping project came to an end in summer 1999. "The GeneMap has since served as the main scaffold for anchoring and orienting the bacterial clone maps that are used in sequencing the human genome," Deloukas says. Jennifer Fisher Wilson is a freelance science writer in Philadelphia. 1. G.D. Schuler et al., "A gene map of the human genome," Science, 274:540-6, Oct. 25, 1996.

The International RH Mapping Consortium

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