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Human Molecular Genetics, 2001, Vol. 10, No. 1 77-83
© 2001 Oxford University Press

X chromosome-specific cDNA arrays: identification of genes that escape from X-inactivation and other applications

Ralf Sudbrak1,+, Georg Wieczorek1,+, Ulrike A. Nuber1, Wolfgang Mann1,§, Roland Kirchner1,§, Fikret Erdogan1, Carolyn J. Brown2, Doris Wöhrle3, Peter Sterk4, Vera M. Kalscheuer1, Wolfgang Berger1, Hans Lehrach1 and Hans-Hilger Ropers1,¶

1Max-Planck Institute for Molecular Genetics, Ihnestrasse 73, D-14195, Berlin, Germany, 2Department of Medical Genetics, University of British Columbia, Vancouver, Canada and 3Department of Medical Genetics, University of Ulm, Germany and 4European Bioinformatics Institute, Hinxton, Cambridge, UK

Mutant alleles are frequently characterized by low expression levels. Therefore, cDNA array-based gene expression profiling may be a promising strategy for identifying gene defects underlying monogenic disorders. To study the potential of this approach, we have generated an X chromosome-specific microarray carrying 2423 cloned cDNA fragments, which represent up to 1317 different X-chromosomal genes. As a prelude to testing cell lines from patients with X-linked disorders, this array was used as a hybridization probe to compare gene expression profiles in lymphoblastoid cell lines from normal males, females and individuals with supernumerary X chromosomes. Measurable hybridization signals were obtained for more than half of the genes represented on the chip. A total of 53 genes showed elevated expression levels in cells with multiple X chromosomes and many of these were found to escape X-inactivation. Moreover, the detection of a male-viable deletion encompassing three genes illustrates the utility of this array for the identification of small unbalanced chromosome rearrangements.

+ These authors contributed equally to this work

§ Present address: MWG Biotech AG, Anzinger Strasse 7, D-85560 Ebersberg, Germany

To whom correspondence should be addressed. Tel: +49 30 8413 1240; Fax: +49 30 8413 1383; Email: ropers@molgen.mpg.de


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