Whitehead Institute, Cambridge, Massachusetts.
Howard Hughes Medical Institute, Whitehead Institute, Cambridge, Massachusetts.
Am J Med Genet C Semin Med Genet. 2019 Mar;181(1):59-67. doi: 10.1002/ajmg.c.31677. Epub 2019 Feb 20.
Sex chromosome constitution varies in the human population, both between the sexes (46,XX females and 46,XY males), and within the sexes (e.g., 45,X and 46,XX females, and 47,XXY and 46,XY males). Coincident with this genetic variation are numerous phenotypic differences between males and females, and individuals with sex chromosome aneuploidy. However, the molecular mechanisms by which sex chromosome constitution impacts phenotypes at the cellular, tissue, and organismal levels remain largely unexplored. Thus, emerges a fundamental question connecting the study of sex differences and sex chromosome aneuploidy syndromes: How does sex chromosome constitution influence phenotype? Here, we focus on Turner syndrome (TS), associated with the 45,X karyotype, and its synergies with the study of sex differences. We review findings from evolutionary studies of the sex chromosomes, which identified genes that are most likely to contribute to phenotypes as a result of variation in sex chromosome constitution. We then explore strategies for investigating the direct effects of the sex chromosomes, and the evidence for specific sex chromosome genes impacting phenotypes. In sum, we argue that integrating the study of TS with sex differences offers a mutually beneficial alliance to identify contributions of the sex chromosomes to human development, health, and disease.
性染色体组成在人类群体中存在差异，包括性别之间（46,XX 女性和 46,XY 男性）和性别内部（例如，45,X 和 46,XX 女性，以及 47,XXY 和 46,XY 男性）。与这种遗传变异相吻合的是男性和女性之间存在许多表型差异，以及性染色体非整倍体的个体。然而，性染色体组成如何影响细胞、组织和机体水平的表型的分子机制在很大程度上仍未得到探索。因此，出现了一个将性别差异和性染色体非整倍体综合征研究联系起来的基本问题：性染色体组成如何影响表型？在这里，我们专注于特纳综合征（TS），其与 45,X 核型相关，并与其与性别差异的研究协同进行。我们回顾了性染色体进化研究的发现，这些研究确定了由于性染色体组成的变异最有可能导致表型的基因。然后，我们探讨了研究性染色体直接影响的策略，以及特定性染色体基因影响表型的证据。总之，我们认为将 TS 的研究与性别差异相结合，为识别性染色体对人类发育、健康和疾病的贡献提供了互利的联盟。
