Shi Lei, Zhang Zhe, Su Bing
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Sci Rep. 2016 Feb 16;6:21181. doi: 10.1038/srep21181.
There are many differences in brain structure and function between males and females. However, how these differences were manifested during development and maintained through adulthood are still unclear. Here we present a time series analyses of genome-wide transcription profiles of the human brain, and we identified genes showing sex biased expression at major developmental stages (prenatal time, early childhood, puberty time and adulthood). We observed a great number of genes (>2,000 genes) showing between-sex expression divergence at all developmental stages with the greatest number (4,164 genes) at puberty time. However, there are little overlap of sex-biased genes among the major developmental stages, an indication of dynamic expression regulation of the sex-biased genes in the brain during development. Notably, the male biased genes are highly enriched for genes involved in neurological and psychiatric disorders like schizophrenia, bipolar disorder, Alzheimer's disease and autism, while no such pattern was seen for the female-biased genes, suggesting that the differences in brain disorder susceptibility between males and females are likely rooted from the sex-biased gene expression regulation during brain development. Collectively, these analyses reveal an important role of sex biased genes in brain development and neurodevelopmental disorders.
男性和女性在大脑结构和功能方面存在许多差异。然而，这些差异在发育过程中是如何表现出来的，以及如何在成年期得以维持，目前仍不清楚。在此，我们对人类大脑的全基因组转录谱进行了时间序列分析，并鉴定出在主要发育阶段（产前、幼儿期、青春期和成年期）表现出性别偏向性表达的基因。我们观察到大量基因（超过2000个基因）在所有发育阶段都表现出性别间表达差异，其中青春期时差异基因数量最多（4164个基因）。然而，主要发育阶段之间性别偏向性基因的重叠很少，这表明大脑中性别偏向性基因在发育过程中存在动态表达调控。值得注意的是，男性偏向性基因高度富集于与精神分裂症、双相情感障碍、阿尔茨海默病和自闭症等神经和精神疾病相关的基因，而女性偏向性基因则没有这种模式，这表明男性和女性在脑部疾病易感性方面的差异可能源于大脑发育过程中的性别偏向性基因表达调控。总体而言，这些分析揭示了性别偏向性基因在大脑发育和神经发育障碍中的重要作用。
