Determination of X-chromosome inactivation status using X-linked expressedpolymorphisms identified by database searching

The large number of redundant sequences available in nucleotide databases p rovides a resource for the identification of polymorphisms. Expressed polym orphisms in X-linked genes can be used to determine the inactivation status of the genes, and polymorphisms in genes that are subject to inactivation can then be used as tools to examine X-chromosome inactivation status in he terozygous females. In this study, we have identified six new X-linked sing le-nucleotide polymorphisms and determined the inactivation status of these genes by examination of expression patterns in female cells previously dem onstrated to have skewed inactivation, as well as by analysis of somatic ce ll hybrids retaining the inactive human X chromosome. Expression was seen f rom both alleles in females heterozygous for the RPS4X gene, confirming the previously reported expression from the inactive X chromosome. Expression of only a single allele was seen in females heterozygous for polymorphisms in the BGN, TM4SF2, ATP6S1, VBP1, and PDHA1 genes, suggesting that these ge nes are subject to X-chromosome inactivation. (C) 2000 Academic Press.