Gylemo Bjorn, Bensberg Maike, Nestor Colm E
Crown Princess Victoria Children´s Hospital, Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden.
Elife. 2025 Jul 17;14:RP102701. doi: 10.7554/eLife.102701.
As females are mosaic for X-inactivation, direct determination of X-linked allelic expression in bulk tissues is typically unfeasible. Using females that are non-mosaic (completely skewed) for X-inactivation (nmXCI) has proven a powerful and natural genetic system for profiling X-inactivation in humans. By combining allele-resolution data for one previously reported and two newly identified nmXCI females, we directly determined X-inactivation status of 380 X-linked genes across 30 normal tissues, including 198 genes for which XCI status is directly determined for the first time. Our findings represent a substantial advance in our understanding of human X-inactivation and will serve as a reference for dissecting the genetic origin of sex bias in human traits. In addition, our study reveals nmXCI as a common feature of the human female population, with profound consequences for the penetrance and expressivity of X-linked traits in humans.
由于雌性在X染色体失活方面是嵌合体，在大块组织中直接确定X连锁等位基因的表达通常是不可行的。使用在X染色体失活方面是非嵌合体（完全偏斜）的雌性（nmXCI）已被证明是一种用于分析人类X染色体失活的强大且天然的遗传系统。通过结合一位先前报道的和两位新鉴定的nmXCI雌性的等位基因解析数据，我们直接确定了30种正常组织中380个X连锁基因的X染色体失活状态，其中包括198个首次直接确定XCI状态的基因。我们的发现代表了我们对人类X染色体失活理解的重大进展，并将作为剖析人类性状性别偏差遗传起源的参考。此外，我们的研究揭示nmXCI是人类女性群体的一个常见特征，对人类X连锁性状的外显率和表现度有深远影响。
