Human sex differences arise from gonadal hormones and sex chromosomes. Studying the direct effects of sex chromosomes in humans is still challenging. Here we studied how the sex chromosomes can modulate gene expression and the outcome of mutations across the genome by exploiting the tendency of cancer cell lines to lose or gain sex chromosomes. We inferred the dosage of the sex chromosomes in 355 female and 408 male cancer cell lines and used it to dissect the contributions of the Y and X Chromosomes to sex-biased gene expression. Furthermore, based on genome-wide CRISPR screens, we identified genes whose essentiality is different between male and female cells depending on the sex chromosomes. The most significant genes were X-linked genes compensated by Y-linked paralogs. Our sex-based analysis identifies genes that, when mutated, can affect male and female cells differently and reinforces the roles of the X and Y Chromosomes in sex-specific cell function.
展开▼
机译：人类的性别差异源于性腺激素和性染色体。研究性染色体对人类的直接影响仍然具有挑战性。在这里，我们研究了性染色体如何通过利用癌细胞系丢失或获得性染色体的趋势来调节基因表达和整个基因组突变的结果。我们推断了 355 个女性和 408 个男性癌细胞系中性染色体的剂量，并用它来剖析 Y 和 X 染色体对性别偏倚基因表达的贡献。此外，基于全基因组 CRISPR 筛选，我们确定了雄性和雌性细胞之间根据性染色体的不同而具有不同本质的基因。最重要的基因是 Y 连锁旁系同源物补偿的 X 连锁基因。我们基于性别的分析确定了基因，这些基因在突变时可以对雄性和雌性细胞产生不同的影响，并加强 X 和 Y 染色体在性别特异性细胞功能中的作用。
展开▼
