A whole-genome radiation hybrid panel and framework map of the
Linda C. McCarthy,
** Marie-Therese Bihoreau,
* Susanna L. Kiguwa,
* Julie Browne,
Takeshi K. Watanabe,
Maria E. Davis,
James R. Hudson, Jr.,
Peter N. Goodfellow,
G. Mark Lathrop,
Michael R. James
Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge, CB2 3EH, UK
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co. Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima, 771-0192, Japan
Research Genetics, 2130 S. Memorial Parkway, Huntsville, AL 35801, USA
Laboratory of Genome Database, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Laboratory of Molecular Medicine, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Received: 17 September 1999 / Accepted: 24 March 2000
The rat is a widely used model organism in medical and pharma-
ceutical research, and its physiology is better understood than that
of any other vertebrate with the exception of human. The rat is a
particularly useful model for investigating polygenic diseases, yet
rat genetics has remained under-researched compared with that of
the mouse (Jacob 1999; James and Lindpaintner 1997). This is
being redressed with the publication of genome-spanning genetic
maps, the production of many thousands of genetic markers (Steen
et al. 1999; Watanabe et al. 1999), and construction of large-insert
clone libraries (loc.cit.). With the availability of these new genetic
and genomic resources, an efficient means of deploying them in
the various disease model studies is required. Radiation hybrid
(RH) mapping is a powerful tool to achieve this goal because it is
rapid, has 100% genome coverage, higher resolution than meiotic
maps, allows for integration of genetic and gene-based markers,
and provides a single resource that can be distributed to any labo-
ratory (McCarthy 1996). Furthermore, non-polymorphic markers
may be RH mapped, a particular advantage for the rat because
genetic maps have limitations because only approximately 50% of
genetic markers are polymorphic in a cross between any two in-
Previously we and others have presented genome-wide maps
based on the T55 RH panel (Steen et al. 1999; Watanabe et al.
1999). Here, we characterize this panel in detail and describe the
optimal subset of RHs with which we have constructed a genome-
wide framework map, which makes this resource immediately use-
ful to everyone involved in genetic studies with this species.
The T55 whole-genome radiation hybrid panel was generated
essentially as described previously (McCarthy et al. 1997). After
an initial characterization of 120 hybrids, 106 were selected to be
commercially grown up on a large scale (Research Genetics Inc.).
The initial phase of our framework map construction used the first
96 hybrids (RHs #1–96), but six of these (RHs #1, 20, 35, 38, 51,
60) were found to have retained no detectable rat DNA, and an-
other four (RHs #11, 15, 54, 90) retained very little rat DNA.
Although the remaining 86 hybrids can produce very robust maps
(Watanabe et al. 1999), we have subsequently screened all remain-
ing RHs for the presence of the 1030 framework markers. The
DNA retained in all 106 RHs is shown in Fig. 1. This work iden-
tified an optimal set of 96 RHs for future mapping, which we
designate as T55v3, which consists of RHs 2–10, 12–14, 16–19,
21–34, 36–37, 39–50, 52–59, 61–89, 91–106. The average reten-
tion frequency of the first 96 RHs from T55v1 is 27%, and this has
increased to 30% for the optimal T55v3 panel. Further information
on the different formats of the panel is available at http://
www.ebi.ac.uk:80/RHdb/panels/T55v1.html. The framework data
which allow mapping using the different versions of T55 are also
available in mapping-ready form at ftp://ftp.well.ox.ac.uk/pub/
genetics. A web-based server has been constructed to allow re-
searchers to map their markers by using our framework maps
(www.otsuka.genome.ad.jp/menu/RH.html). This RH server al-
lows the user to choose the version of the RH panel and corre-
sponding framework map that are appropriate.
* These authors contributed equally to this work.
Correspondence to: M.R. James; E-mail: firstname.lastname@example.org; or
to L.C. McCarthy; E-mail: lm93678@GlaxoWellcome.co.uk
** Present address: Molecular Genetics, GlaxoWellcome Medicines Re-
search Centre, Gunnels Wood Road, Stevenage SGN 2NY, U.K.
*** Present address: SmithKline Beecham Pharmaceuticals, New Fron-
tiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, U.K.
Fig. 1. DNA content of radiation hybrids. Shown are the data from scoring
all 106 RHs of the commercially available T55 panel for the 1030 markers
that form the 1000:1 odds framework map. The solid filled columns indi-
cate the 96 RHs that constitute the optimal subset (T55v3).
Mammalian Genome 11, 791–795 (2000).
© Springer-Verlag New York Inc. 2000