Radiation Hybrid Mapping


Radiation hybrid mapping is a method that combines aspects of both genetic and physical mapping and is extensively used in the construction of whole‐genome maps. A panel of radiation hybrid cell lines, each retaining a different portion of the donor genome in the background of a recipient cell, is used to score the presence or absence of sequence tagged sites.

Keywords: radiation hybrids; panels; mapping; map; genome

Figure 1.

Schematic drawing illustrating the main steps in the construction of radiation hybrid (RH) panels. The parameters used in the construction of the Genebridge 4 (Gyapay et al., ) panel are given as an example. The human diploid fibroblast cell line HFL121 (donor) is irradiated with 3000 rad and fused to A23 TK (deficient in thymidine kinase) hamster cells (recipient). The hybrids are selected in hypoxanthine–aminopterin–thymidine (HAT) medium on which the hamster cells that have not retained a fragment harboring the human TK gene are unable to grow. The irradiation dose is lethal to the human cells. The donor DNA fragments (white bars) are retained as extra chromosomes or they integrate into the hamster chromosomes (black bars). Hybrids that form individual colonies are picked and further characterized using a small set of genome‐wide markers. Typically, on the basis of their retention characteristics a set of ca. 100 hybrids is assembled into the mapping panel. PEG: polyethylene glycol.



Avner P, Bruls T, Poras I, et al. (2001) A radiation hybrid transcript map of the mouse genome. Nature Genetics 29: 194–200.

Benham F, Hart K, Crolla J, et al. (1989) A method for generating hybrids containing nonselected fragments of human chromosomes. Genomics 4: 509–517.

Bentley DR, Deloukas P, Dunham A, et al. (2001) The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X. Nature 409: 942–943.

Breen M, Jouquand S, Renier C, et al. (2001) Chromosome‐specific single‐locus FISH probes allow anchorage of an 1800‐marker integrated radiation‐hybrid/linkage map of the domestic dog genome to all chromosomes. Genome Research 11: 1784–1795.

Cox DR, Burmeister M, Price ER, Kim S and Myers RM (1990) Radiation hybrid mapping: a somatic cell genetic method for constructing high‐resolution maps of mammalian chromosomes. Science 250: 245–250.

Deloukas P (2001a) Map integration: from a genetic map to a physical gene map and ultimately to the sequence map. In: Starkey MP and Elaswarapu R (eds.) Methods in Molecular Biology: Genomics Protocols, vol. 175, pp. 130–142. Totowa, NJ: Humana Press Inc.

Deloukas P (2001b) Construction of transcript maps by somatic cell/radiation hybrid mapping – the human gene map. In: Sarkey MP and Elaswarapu R (eds.) Methods in Molecular Biology: Genomics Protocols, vol. 175, pp. 155–168. Totowa, NJ: Humana Press Inc.

Deloukas P, Schuler GD, Gyapay G, et al. (1998) A physical map of 30000 human genes. Science 282: 744–746.

Geisler R, Rauch GJ, Baier H, et al. (1999) A radiation hybrid map of the zebrafish genome. Nature Genetics 23: 86–89.

Goss SJ and Harris H (1975) New method for mapping genes in human chromosomes. Nature 255: 680–684.

Goss SJ and Harris H (1977) Gene transfer by means of cell fusion I. Statistical mapping of the human X‐chromosome by analysis of radiation‐induced gene segregation. Journal of Cell Science 25: 17–37.

Gyapay G, Schmitt K, Fizames C, et al. (1996) A radiation hybrid map of the human genome. Human Molecular Genetics 5: 339–346.

Hudson TJ, Church DM, Greenaway S, et al. (2001) A radiation hybrid map of mouse genes. Nature Genetics 29: 201–205.

Hudson TJ, Stein LD, Gerety SS, et al. (1995) An STS‐based map of the human genome. Science 270: 1945–1954.

Hukriede NA, Joly L, Tsang M, et al. (1999) Radiation hybrid mapping of the zebrafish genome. Proceedings of the National Academy of Sciences of the United States of America 96: 9745–9750.

Hukriede N, Fisher D, Epstein J, et al. (2001) The LN54 radiation hybrid map of zebrafish expressed sequences. Genome Research 11: 2127–2132.

Kiguwa SL, Hextall P, Smith AL, et al. (2000) A horse whole‐genome‐radiation hybrid panel: chromosome 1 and 10 preliminary maps. Mammalian Genome 11: 803–805.

Kwok C, Korn RM, Davis ME, et al. (1998) Characterization of whole genome radiation hybrid mapping resources for non‐mammalian vertebrates. Nucleic Acids Research 26: 3562–3566.

Lunetta KL, Boehnke M, Lange K and Cox DR (1996) Selected locus and multiple panel models for radiation hybrid mapping. American Journal of Human Genetics 59: 717–725.

Matise TC, Perlin M and Chakravarti A (1994) Automated construction of genetic linkage maps using an expert system (MultiMap): a human genome linkage map. Nature Genetics 6: 384–390.

McCarthy LC, Terrett J, Davis ME, et al. (1997) A first‐generation whole genome‐radiation hybrid map spanning the mouse genome. Genome Research 7: 1153–1161.

Naylor LS (1997) Construction and use of somatic cell hybrids. In: Dear PH (ed.) Genome Mapping: A Practical Approach, pp. 125–163. Oxford, UK: IRL/Oxford University Press.

Olivier M, Aggarwal A, Allen J, et al. (2001) A high‐resolution radiation hybrid map of the human genome draft sequence. Science 291: 1298–1302.

Priat C, Hitte C, Vignaux F, et al. (1998) A whole‐genome radiation hybrid map of the dog genome. Genomics 54: 361–378.

Schuler GD, Boguski MS, Stewart EA, et al. (1996) A gene map of the human genome. Science 274: 540–546.

Slonim D, Kruglyak L, Stein L and Lander E (1997) Building human genome maps with radiation hybrids. Journal of Computational Biology 4: 487–504.

Stewart EA and Cox DR (1997) Radiation hybrid mapping. In:Dear PH (ed.) Genome Mapping: A Practical Approach, pp. 73–93. Oxford, UK: IRL Press.

Stewart EA, McKusick KB, Aggarwal A, et al. (1997) An STS‐based radiation hybrid map of the human genome. Genome Research 7: 422–433.

Walter MA, Spillett DJ, Thomas P, Weissenbach J and Goodfellow PN (1994) A method for constructing radiation hybrid maps of whole genomes. Nature Genetics 7: 22–28.

Watanabe TK, Bihoreau MT, McCarthy LC, et al. (1999) A radiation hybrid map of the rat genome containing 5255 markers. Nature Genetics 22: 27–36.

Westerveld A, Visser RPLS, Khan PM and Bootsma D (1971) Loss of human genetic markers in man–Chinese hamster somatic cell hybrids. Nature New Biology 234: 20–22.

Womack JE, Johnson JS, Owens EK, et al. (1997) A whole‐genome radiation hybrid panel for bovine gene mapping. Mammalian Genome 8: 854–856.

Yerle M, Pinton P, Robic A, et al. (1998) Construction of a whole‐genome radiation hybrid panel for high‐resolution gene mapping in pigs. Cytogenetics and Cell Genetics 82: 182–188.

Further Reading

Agarwala R, Applegate DL, Maglott D, Schuler GD and Schaffer AA (2000) A fast and scalable radiation hybrid map construction and integration strategy. Genome Research 10: 350–364.

Ben‐Dor A and Chor B (1997) On constructing radiation hybrid maps. Journal of Computational Biology 4: 517–533.

Hawken RJ, Murtaugh J, Flickinger GH, et al. (2000) A first‐generation porcine whole‐genome radiation hybrid map. Mammalian Genome 10: 824–830.

Jones HB (1996) Hybrid selection as a method of increasing mapping power for radiation hybrids. Genome Research 6: 761–769.

Lunetta KL and Boehnke M (1994) Multipoint radiation hybrid mapping: comparison of methods, sample size requirements, and optimal study characteristics. Genomics 21(1): 92–103.

McCarthy LC, Bihoreau MT, Kiguwa SL, et al. (2000) A whole‐genome radiation hybrid panel and framework map of the rat genome. Mammalian Genome 11: 791–795.

Newell W, Beck S, Lehrach H and Lyall A (1998) Estimation of distances and map construction using radiation hybrids. Genome Research 8: 493–508.

Rexroad III CE, Owens EK, Johnson JS and Womack JE (2000) A 12000 rad whole genome radiation hybrid panel for high resolution mapping in cattle: characterization of the centromeric end of chromosome 1. Animal Genetics 31: 262–265.

Riera‐Lizarazu O, Vales MI, Ananiev EV, Rines HW and Phillips RL (2000) Production and characterization of maize chromosome 9 radiation hybrids derived from an oat–maize addition line. Genetics 156: 327–339.

Soderlund C, Lau T and Deloukas P (1998) Z extensions to the RHMAPPER package. BioInformatics 14: 538–539.

Stringham HM, Boehnke M and Lange K (1999) Point and interval estimates of marker location in radiation hybrid mapping. American Journal of Human Genetics 65: 545–553.

Web Links

PRIMER version 3 http://www‐genome.wi.mit.edu/cgi‐bin/primer/primer3_www.cgi


MULTIMAP http://linkage.rockefeller.edu/multimap

RHMAP http://www.sph.umich.edu/group/statgen

RHMAPPER http://www.genome.wi.mit.edu/ftp/pub/software/rhmapper

SAMAPPER http://shgc.stanford.edu

Additional software tools http://compgen.rutgers.edu/rhmap/#programs/

Research Genetics http://www.resgen.com/intro/mapping.php3

WGRH panels http://compgen.rutgers.edu/rhmap

RHdb. Source of RH vectors, hosted by the European Bioinformatics Institute http://www.ebi.ac.uk:80/RHdb/

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Deloukas, Panos(Sep 2005) Radiation Hybrid Mapping. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005361]