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We are collecting data on DBCRs in a global network, Mendelian Cytogenetics Network, to identify breakpoints which are associated with specific disorders and ultimately to identify novel disease-genes. The collaboration was initiated because DBCRs are so rare and heterogeneous, that an optimal study of them can only be done if many laboratories are involved. It was also initiated because it was realised, that if all cytogenetic laboratories joined efforts, an important resource for future identification of human genotype-phenotype associations could be established.
Chromosome analysis using banding techniques have been performed in most countries for the last 10-30 years, and every cytogenetic laboratory has or will encounter DBCRs. Usually it is not possible to establish the direct clinical implications of the individual rearrangement, so DBCRs are seldomly reported in the litterature. As a consequence, thousands of unreported DBCRs are hidden in the files of routine cytogenetic laboratories. Furthermore, DBCRs may not only be linked to rare disorders. Specific examples show, that even if DBCR-carriers later in life develop additional symptoms, e.g. cancer or other late onset disorders, the potential importance of the chromosome defect is seldomly recognized.
Most disease-causing mutations are below the resolution of the microscope, but microscopically visible DBCRs that truncate, delete or otherwise inactivate genes have regularly been reported. The unique value of DBCRs with respect to positional cloning/candidate gene identification lie in the associated alteration at the DNA level, that often can be used for directed search for the gene of interest. Although the mechanism behind DBCRs in many cases involves direct truncation of the responsible gene locus, submicroscopic deletions, long range position effects and hypothetical chromosomal domain effects may also be revealed.
The aim of mcndb is to centralize available published and unpublished information on DBCRs. mcndb presently contain >2700 DBCRs; the database will be developed into a tool that can link breakpoints and phenotypes with other genomic, functional and disease databases.
For a longer description of the goals and ideas behind the MCN you should read Mendelian Cytogenetics Network (MCN): Systematic identification of disease genes by structural chromosome rearrangements.