Allele-specific X-linked gene activity in normal human cells assayed by expressed single nucleotide polymorphisms (cSNPs).

Abstract

In mammals, dosage compensation at X-linked loci is achieved by the process of X chromosome inactivation in the homogametic sex. While most genes on the inactive X chromosome (Xi) are subjected to transcriptional inactivation, some escape inactivation and present biallelic expression. The expression status of X-linked genes has been extensively studied in somatic cell hybrids containing only the human Xi. Although this approach has recently been used to generate a profile of X-linked gene activity, it may not reflect what happens in a normal human cell. The recent development of a database of single nucleotide polymorphisms (SNPs) throughout the human genome enables investigation of allele-specific gene expression in normal human cells. In this study, we established a panel of X-linked expressed SNPs (cSNPs). These markers were used for monitoring gene expression in primary human fibroblast cell lines with completely skewed XCI, demonstrating the potential of this system for studying X-linked gene expression in normal human cells.