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Human genome technology

10 Mb, was subsequently published by the same group (Chumakov et al, 1992). While these physical maps were recognised to be far from complete, this was an outstanding achievement and provided a good frame work for the scientific community to build upon in order to produce further detailed maps of all the chromosomes. Complementing this approach, good STS-based physical maps of the human genome have been developed, such as the one constructed at the Whitehead institute in Massachussetts (Hudson et al., 1995). These have been achieved in part by mapping STSs against panels of whole-genome radiation hybrids. Radiation hybrids as previously discussed, derived from monochromosomal hybrid donor cells have been superceded by whole genome radiation hybrids where the donor is an irradiated normal human diploid cell. The first such panel consisted of 199 hybrids made by fusing an irradiated 46, XY human fibroblast cell line to TK- hamster cells (Walter et al., 1994). Gyapay et al., (1996) used 404 microsatallite markers of known location to show that this hybrid panel could generate accurate maps, and then used it to map 374 unmapped ESTs. A subset of 93 of the hybrids has been made widely available as the Genebridge 4 panel. The 93 hybrids average 32% retention of any particular human sequence, with the average fragment size of 25 Mb. Laboratories can map any unknown STS by scoring the 93 Genebridge hybrids and comparing the pattern with the patterns previously mapped markers held on a central server (fig 10.4).This turned out to be an extremely powerful and convenient tool for physical mapping any STS or EST. A second human-hamster panel, Stanford G3, was made using a higher dose of radiation, so that the average human size is smaller. The 83 hybrids in the G3 average 16% retention of the human genome, with an average fragment size f 2.4 Mb. Thus G3 can be used for fine mapping (Deloukas et al., 1998). However, the utility of theYAC contig map...

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