In collaboration with the Mendelian Cytogenetic Network (MCN, coordinator:N. Tommerup, Copenhagen http://www.mcndb.imbg.ku.dk) we develop a valuable tool that will allow the definition and detailed characterization of chromosome breakpoints across the human genome.

To date, the clone repository contains approx. 3000 genetically and physically mapped Mega Yeast Artificial Chromosomes (YACs) which cover more than half of the genome (Table 1) and >2500 PAC and BAC clones. This unique resource of arrayed YAC/BAC/PAC clones will allow the mapping of all chromosome aberrations in a short period of time, and to obtain a candidate clone set for fine mapping and gene isolation. Information on the YAC clone distribution along each chromosome and more details on clones are accessible in a user-friendly database (Probe Mapping Data).

Obtaining clones 

Standardized FISH probes from the clone set will be provided to all members of the MCN and can be requested either directly from the MPI (contact: Dr. Vera Kalscheuer, Berlin, kalscheu@molgen.mpg.de) or from the MCN (contact: Dr. Niels Tommerup, Copenhagen, tommerup@imbg.ku.dk). We initially distribute three well scattered clones for each cytogenetic region of interest. The probes are PCR products and need to be reamplified by standard DOP-PCR. Reporting of the mapping results is a prerequisite for obtaining new clones and will ensure an optimized selection for narrowing the breakpoint region. All results will be handled confidentially. We also assist with FISH mapping, the identification of breakpoint-spanning clones and with the search for genes in the breakpoint region.

Telomere YACs 

The chromosome ends may represent a major source of human pathology that has not been previously appreciated. Recent studies showed that unexplained mental retardation may be accounted for by relatively small telomere abnormalities. Therefore, in collaboration with Jonathan Flint (Institute of Molecular Medicine, Oxford), we provide DNA of individual telomere-specific BAC/PAC clones to all cytogenetic laboratories which want to screen their cases for possible telomere rearrangements. The clones map in a distance of ~300 kb from the end of the chromosome. Furthermore, we provide representative subtelomeric YAC probes for all human chromosome ends. Interested laboratories chould contact Dr. Vera Kalscheuer (kalscheu@molgen.mpg.de).