The objective of this project is to provide an integrated physical, genetic and functional map of a large region of the human X chromosome, which corresponds roughly to the Xp22 band ( 15 to 20 Mb).
At present, there is very little physical map information: no YAC contigs or PFGE maps have been reported, few chromosomal breakpoints were available for ordering markers until very recently.
Partial genetic maps have been published, but they have a low density and all available markers have not been integrated in a single genetic map. Although general mapping efforts, as developed in GENETHON are likely to provide, within the next two years, YAC contigs and genetic maps over the whole genome, these maps will not have the precision, completeness and validation that are needed to identify disease genes or as a prerequisite for sequencing regions of interest.
Our goal is to provide complete coverage in validated YAC contigs of the region, to map its CpG islands and estimate gene density, and to identify expressed genes in regions of special interest.
A high density genetic map will be constructed and the polymorphic markers integrated in the YAC contig map.
A common data base format will be used that will allow efficient integration of the results generated by the collaboration in public data bases This study includes some more specific aims of biological and medical interest.
The analysis of inactivation status of genes in the Xp22.3 region will determine whether genes that escape inactivation are clustered and show a clear boundary with genes that are subject to X inactivation, or whether there is interspersion of the two type of genes.
Members of the collaboration have important patients and family material that should allow precise mapping and identification of several disease genes which notably include: retinoschisis (an important cause of severe visual impairment), Coffin-Lowry syndrome (a pleiotropic disorder with mental retardation and severe skeletal deformations), x-linked hypophosphataemic rickets (a defect in the control of phosphate metabolism and the most common form of vitamin-D resistant rickets) and a gene implicated in sex determination, the function of which appears uniquely sensitive of dosage.
Funding SchemeCSC - Cost-sharing contracts
WC2A 3PX London
W1N 8AA London
CB2 3EH Cambridge