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

Mutant alleles are frequently characterized by low expression levels. There fore, cDNA array-based gene expression profiling may be a promising strateg y for identifying gene defects underlying monogenic disorders. To study the potential of this approach, we have generated an X chromosome-specific mic roarray carrying 2423 cloned cDNA fragments, which represent up to 1317 dif ferent X-chromosomal genes. As a prelude to testing cell lines from patient s with X-linked disorders, this array was used as a hybridization probe to compare gene expression profiles in lymphoblastoid cell lines from normal m ales, females and individuals with supernumerary X chromosomes. Measurable hybridization signals were obtained for more than half of the genes represe nted 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 encompassin g three genes illustrates the utility of this array for the identification of small unbalanced chromosome rearrangements.