High-Resolution Landmark Framework for the Sequence-Ready Mapping of Xq23–q26.1

The complete sequence of the human genome is being determined as an international collaborative effort with the work proceeding on a chromosome-by-chromosome basis. Essential to the co-ordination of the work on individual chromosomes is the availability of an accurate framework map of landmarks (Bentley et al. 1998). Landmarks are used to construct the sequence-ready map in bacterial clones, to integrate confirmatory map data from other sources, and to define boundaries between sequencing groups. The last is particularly relevant to the sequencing of the human X chromosome in view of the large number of participating groups (see http://webace.sanger.ac.uk/HGP/). Whole genome landmark framework maps have been produced by genetic linkage (Murray et al. 1994; Dib et al. 1996), by yeast artificial chromosome (YAC) content mapping (Chumakov et al. 1995; Hudson et al. 1995), and by radiation hybrid (RH) mapping (Hudson et al. 1995; Schuler et al. 1996; Stewart et al. 1997; Deloukas et al. 1998). The STS density of these maps (2–10 markers/Mb) is too low for the assembly of bacterial clone contigs over long distances, even when using large-insert bacterial and P1 artificial chromosome libraries [(BAC) Shizuya et al. 1992; (PAC) Ioannou et al. 1994]. There is a need, therefore, to produce higher density framework maps (15–20 markers per Mb) using RH mapping or YACs. The need is particularly acute for the X chromosome, because neither the whole genome RH maps nor the genetic maps provide ordered landmarks at a density equivalent to that obtained for the autosomes. Although there are particular limitations to the X chromosome framework map generated by whole genome approaches, the intense interest in X-linked disease genes has ensured the rapid progress of YAC contig assembly and landmark ordering over most of the chromosome. The editorial committees of successive X chromosome workshops have produced consensus landmark maps based on these individual regional efforts. The latest such map, the product of the Seventh X Chromosome Workshop (Sanger Centre, 1–4 October 1996), showed YAC continuity over most of the chromosome (X Chromosome Editorial Committee, unpubl.). At this time, the region between proximal Xq23 and proximal Xq26 was furthest from completion. In this work we report a high-resolution landmark framework map of this part of the X chromosome and summarize the progress made in the sequence-ready mapping of the region.