In meiosis, homologous chromosome synapsis is mediated by a supramolecular protein structure, the synaptonemal complex (SC), that assembles between homologous chromosome axes. The mammalian SC comprises at least eight largely coiled-coil proteins that interact and self-assemble to generate a long, zipper-like structure that holds homologous chromosomes in close proximity and promotes the formation of genetic crossovers and accurate meiotic chromosome segregation. In recent years, numerous mutations in human SC genes have been associated with different types of male and female infertility. Here, we integrate structural information on the human SC with mouse and human genetics to describe the molecular mechanisms by which SC mutations can result in human infertility. We outline certain themes in which different SC proteins are susceptible to different types of disease mutation and how genetic variants with seemingly minor effects on SC proteins may act as dominant-negative mutations in which the heterozygous state is pathogenic.

中文翻译：

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减数分裂染色体结构、联会复合体和不孕症

在减数分裂中，同源染色体联会是由超分子蛋白质结构（联会复合体（SC））介导的，该结构在同源染色体轴之间组装。哺乳动物 SC 包含至少八个主要卷曲螺旋蛋白，这些蛋白相互作用并自组装，生成长的拉链状结构，使同源染色体紧密相连，并促进遗传交叉和准确的减数分裂染色体分离的形成。近年来，人类 SC 基因的大量突变与不同类型的男性和女性不育症有关。在这里，我们将人类 SC 的结构信息与小鼠和人类遗传学相结合，以描述 SC 突变导致人类不育的分子机制。我们概述了某些主题，其中不同的 SC 蛋白容易受到不同类型的疾病突变的影响，以及看似对 SC 蛋白影响较小的遗传变异如何充当显性失活突变，其中杂合状态是致病的。