Data from: Characterization of human cortical gene expression in relation to glucose utilization.

Objectives:
Human brain development follows a unique pattern characterized by a prolonged period of postnatal growth and reorganization, and a postnatal peak in glucose utilization. The molecular processes underlying these developmental changes are poorly characterized. The objectives of this study were to determine developmental trajectories of gene expression and to examine the evolutionary history of genes differentially expressed as a function of age.
Methods:
We used microarrays to determine age-related patterns of mRNA expression in human cerebral cortical samples ranging from infancy to adulthood. In contrast to previous developmental gene expression studies of human neocortex that relied on postmortem tissue, we measured mRNA expression from the nondiseased margins of surgically resected tissue. We used regression models designed to identify transcripts that followed significant linear or curvilinear functions of age and used population genetics techniques to examine the evolution of these genes.
Results:
We identified 40 transcripts with significant age-related trajectories in expression. Ten genes have documented roles in nervous system development and energy metabolism, others are novel candidates in brain development. Sixteen transcripts showed similar patterns of expression, characterized by decreasing expression during childhood. Comparative genomic analyses revealed that the regulatory regions of three genes have evidence of adaptive evolution in recent human evolution.
Conclusions:
These findings provide evidence that a subset of genes expressed in the human cerebral cortex broadly mirror developmental patterns of cortical glucose consumption. Whether there is a causal relationship between gene expression and glucose utilization remains to be determined.

研究目标：
人类大脑发育遵循独特模式，其特征为产后生长与重塑的周期漫长，且产后葡萄糖代谢达到峰值。目前对于这些发育变化背后的分子机制，尚缺乏充分解析。本研究的目标在于明确基因表达的发育轨迹，并解析随年龄呈现差异表达的基因的进化历程。

研究方法：
我们采用基因芯片（microarray）技术，对从婴儿期至成年期的人类大脑皮层样本中的mRNA表达年龄相关模式进行检测。与此前依赖尸检组织开展的人类新皮层发育基因表达研究不同，本研究的mRNA表达数据取自手术切除组织的非病变边缘区域。我们采用回归模型，以识别出表达随年龄呈现显著线性或曲线变化规律的转录本（transcript），并运用群体遗传学技术解析这些基因的进化过程。

研究结果：
本研究共鉴定出40个表达随年龄呈现显著发育轨迹的转录本。其中10个基因已被证实参与神经系统发育与能量代谢过程，其余基因则为脑发育研究中的新型候选基因。另有16个转录本呈现相似的表达模式，表现为儿童期表达水平持续下调。比较基因组分析结果显示，3个基因的调控区域在人类近期进化过程中存在适应性进化的证据。

研究结论：
本研究结果证实，人类大脑皮层中表达的部分基因，其表达模式与皮层葡萄糖消耗的发育模式高度吻合。基因表达与葡萄糖利用率之间是否存在因果关系，仍有待进一步研究探明。