Genes that escape X-inactivation in humans have high intraspecific variability in expression, are associated with mental impairment but are not slow evolving
Por:
Zhang Y., Castillo-Morales A., Jiang M., Zhu Y., Hu L., Urrutia A.O., Kong X., Hurst L.D.
Publicada:
1 ene 2013
Resumen:
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. © 2013 The Author.
Filiaciones:
Zhang Y.:
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Graduate School of the Chinese Academy of Sciences, Beijing, China
Castillo-Morales A.:
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom
Jiang M.:
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Zhu Y.:
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Hu L.:
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Urrutia A.O.:
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom
Kong X.:
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Hurst L.D.:
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom
Bronze
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