International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)


A23. Radiation Hybrid Mapping of Mouse Expressed Sequence Tags (ESTs)

C. Heuston1, A.R. Haynes1, C. Davison1, P.J. Trickett1, A. Southwell1, S. Greenaway 1, M.A.Strivens1, R. Hardisty1, J. Yang1, A. Varela-Carver1, H. Doi3, J. Kitchen3, M.S.H. Ko4, S.D.M. Brown1 and P. Denny1.
1MRC UK Mouse Genome Centre and Mammalian Genetics Unit, Harwell, OX11 ORD, UK.
2The Rockefeller University, 1230 York Ave, Box 192, New York, NY, USA.
3ERATO Doi Bioasymmetry Project, Wayne State University, Detroit, MI 48202, USA.
4Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

The use of the positional candidate approach(1) to identify genes likely to be responsible for a mutant phenotype is still problematic in mouse. This is due to the relatively sparse transcript map - about 7900 mapped genes. Several groups, including our own, are mapping ESTs as a way to increase the density of transcript maps and hence increase the likelihood of finding candidates for any novel mutation.

We are mapping ESTs using a radiation hybrid (RH) panel (Research Genetics), as this approach has several advantages over traditional meiotic mapping. The ESTs we have mapped so far come from libraries derived from peri-implantation or gastrulation stages of gestation, as these stages are particularly enriched in novel transcripts. Our emphasis has now shifted to novel ESTs expressed in the newborn inner ear. This is intended to support research into the molecular genetics of deafness at MRC Harwell, supplying candidate genes for mutants arising from the Mutagenesis Programme(2).

We have mapped over 2000 ESTs at the time of writing and aim to map about 5,000 over the next 2 years. We are currently placing ~50 ESTs each week on the MIT/Whitehead framework maps(3).

As part of the quality assessment of the EST map data, we have included a large number of ESTs that have also been genetically mapped and found that over 96% of the markers map to the appropriate genomic region. For details of our EST map data, see our website:

http://www.mgc.har.mrc.ac.uk/

1.

1 Collins, F.S. (1995) Nat Genet 9, 347-50

2.

2 Nolan P et al (2000) Nat Genet. (in press)

3.

3 Van Etten et al (1999) Nat Genet 9, 347-50


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