In female mammals most X-linked genes are subject to X-inactivation. However, in 
humans some X-linked genes escape silencing, these escapees being candidates for 
the phenotypic aberrations seen in polyX karyotypes. These escape genes have 
been reported to be under stronger purifying selection than other X-linked 
genes. Although it is known that escape from X-inactivation is much more common 
in humans than in mice, systematic assays of escape in humans have to date 
employed only interspecies somatic cell hybrids. Here we provide the first 
systematic next-generation sequencing analysis of escape in a human cell line. 
We analyzed RNA and genotype sequencing data obtained from B lymphocyte cell 
lines derived from Europeans (CEU) and Yorubans (YRI). By replicated detection 
of heterozygosis in the transcriptome, we identified 114 escaping genes, 
including 76 not previously known to be escapees. The newly described escape 
genes cluster on the X chromosome in the same chromosomal regions as the 
previously known escapees. There is an excess of escaping genes associated with 
mental retardation, consistent with this being a common phenotype of polyX 
phenotypes. We find both differences between populations and between individuals 
in the propensity to escape. Indeed, we provide the first evidence for there 
being both hyper- and hypo-escapee females in the human population, consistent 
with the highly variable phenotypic presentation of polyX karyotypes. 
Considering also prior data, we reclassify genes as being always, never, and 
sometimes escape genes. We fail to replicate the prior claim that genes that 
escape X-inactivation are under stronger purifying selection than others.