Participants involved: Berlin (responsible), Nijmegen, Paris, Leuven, Tours.
Collaborating institutes: Lyon, Nicosia, Poznan.

Objectives

Identification of MRX candidate genes by positional cloning. X-chromosomal breakpoints found in translocations and inversions in mentally retarded individuals will be characterized to find new MRX genes.

Methodology and study materials

Material will be collected from individuals with mental retardation coinciding with an X-chromosomal breakpoint (all partners involved in this work package).

EBV-transformed lymphoblastoid cell lines will be generated (all partners involved in this work package).

Fine-mapping of the X-chromosomal breakpoint will be done with fluorescent in situ hybridisation (FISH). A PCR-ready collection of YAC clones covering the entire X chromosome is available for the FISH analyses (participant Berlin).

Genes will be identified in YAC, PAC, cosmid clones spanning the X-chromosomal breakpoint. Moreover, identification of X-chromosomal genes that are disrupted by the chromosomal breakpoint will be undertaken by bio-informatic analysis of the Humane Genome Sequence (participant Berlin). Physical evidence will be provided for disruption of the gene structure or its expression (participant Berlin).

MRX candidate genes will be tested further as described in work package 5.