Mol Biol Evol ：揭示X染色体逃逸基因或和个体精神损伤相关

近日，刊登在国际杂志Molecular Biology and Evolution上的一篇研究文章中，来自英国巴斯大学的研究者通过研究，在机体X染色体上发现了很多数量的“逃逸基因”，而且这些基因在此前研究中并未发现过；该研究为科学家理解人类的精神损伤疾病提供了一定思路。女性，并不像男性，其具有一对X染色体，这样的遗传构成提出了一系列有趣的遗传难题，也就是说在额外的这个X染色体上到底会发生什么？如果所有的基因都开始表达，那么女性的外在表现将会是男性外在表现的两倍。

研究者表示，在女性机体内，一种名为X染色体失活的过程会使得其中一个X染色体全部失去功能，从而使得基因不能够进行过度表达。然而此过程并不是总会按照预期进行“工作”，有些基因就可以悄无声息地逃脱失活这个过程，这种情况在一千个出生的女孩儿中会有一例，出生的女孩儿会携带有XXX染色体，而不是XX染色体，这将会对这种个体的成长以及精神状况产生非常严重的影响。

研究者Laurence Hurst发现，X染色体上有114个基因可以逃脱X染色体的失活过程，其中的76个基因此前并未鉴别过。这些鉴别过的基因都位于X染色体的某个区域。在某些个体中有80个基因都可以发生逃逸，这些逃逸的基因具有极大的变异能力，而且可以快速进化。

最后研究者表示，这项研究中他们发现了从X染色体失活过程中逃逸的22个基因，而且这些基因和个体精神功能直接相关，研究者希望这项研究将为研究XXX染色体综合征以及个体的精神障碍提供帮助和思路。（转化医学网360zhyx.com）

原文链接：

---

Genes that escape X-inactivation in humans have high intraspecific variability in expression, are associated with mental impairment but are not slow evolving.

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. While 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.

来源：生物谷