School of Molecular Biosciences, Washington State University, Pullman, Washington 99164, USA.
Biol Reprod. 2012 Apr 5;86(4):102. doi: 10.1095/biolreprod.111.095216. Print 2012 Apr.
Prophase is a critical stage of meiosis, during which recombination-the landmark event of meiosis-exchanges information between homologous chromosomes. The intractability of mammalian gonads has limited our knowledge on genes or interactions between genes during this key stage. Microarray profiling of gonads in both sexes has generated genome-scale information. However, the asynchronous development of germ cells and the mixed germ/somatic cell population complicate the use of this resource. To elucidate functional networks of meiotic prophase, we have integrated global gene expression with other genome-scale datasets either within or across species. Our computational approaches provide a comprehensive understanding of interactions between genes and can prioritize candidates for targeted experiments. Here, we examined two novel prophase genes predicted by computational models: Ankrd17 and Anapc10. Their expression and localization were characterized in the developing mouse testis using in situ hybridization and immunofluorescence. We found ANKRD17 expression was predominantly restricted to pachytene spermatocytes and round spermatids. ANKRD17 was diffusely distributed throughout the nucleus of pachytene cells but excluded from the XY body and other heterochromatic regions. ANAPC10 was mainly expressed in the cytoplasm of spermatogonia and leptotene and pachytene spermatocytes. These experiments support our computational predictions of Ankrd17 and Anapc10 as potential prophase genes. More importantly, they serve as a proof of concept of our integrative computational and experimental approach, which has delivered a larger candidate gene set to the broader reproductive community.
前期是减数分裂的一个关键阶段，在此期间，重组——减数分裂的标志性事件——在同源染色体之间交换信息。哺乳动物性腺的难以处理限制了我们对这个关键阶段的基因或基因之间相互作用的了解。对两性性腺进行的微阵列分析产生了基因组规模的信息。然而，生殖细胞的异步发育和生殖细胞与体细胞的混合群体使该资源的使用变得复杂。为了阐明减数分裂前期的功能网络，我们已经将全局基因表达与其他基因组规模数据集整合在一起，无论是在同一物种内还是跨物种。我们的计算方法提供了对基因之间相互作用的全面理解，并可以优先考虑针对靶向实验的候选者。在这里，我们通过计算模型预测了两个新的前期基因：ANKRD17 和 Anapc10。我们使用原位杂交和免疫荧光法在发育中的小鼠睾丸中对其表达和定位进行了研究。我们发现 ANKRD17 的表达主要局限于粗线期精母细胞和圆形精子细胞。ANKRD17 在粗线期细胞的核内呈弥散分布，但被排除在 XY 体和其他异染色质区域之外。ANAPC10 主要在精原细胞和细线期和粗线期精母细胞的细胞质中表达。这些实验支持了我们对 Ankrd17 和 Anapc10 作为潜在前期基因的计算预测。更重要的是，它们为我们的整合计算和实验方法提供了一个概念验证，该方法为更广泛的生殖社区提供了更大的候选基因集。
