• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Gene expression abnormalities in the autistic brain.
【24h】

Gene expression abnormalities in the autistic brain.

机译：自闭症大脑中的基因表达异常。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Although it is accepted that autism is a highly heritable neurodevelopmental disorder that exhibits brain overgrowth in early years of life, underlying genetic mechanisms of this abnormal developmentremain unknown. It has been long hypothesized that autism begins prenatally due to abnormal cell proliferation, cell number regulation, and cell migration functions as the cortex is formed. These possibilities have never been systematically examined in the young developing autistic cerebral cortex, in part due to the limitations of tissue preservation quality. We aimed to test these hypotheses through genome-wide expression profiling and RTPCRon mRNA from postmortem brain tissue of young autistic and control cases. To yield the most reliable dataset with the largest sample size possible for this analysis, we first compared in vitro transcription (IVT)- and cDNA-mediated Annealing Selection and Ligation (DASL)-based expression platforms on partially degraded RNA from reference pools, and frozen and formalin fixed postmortem brain tissue. Results suggested that the DASL-based platform produced more reliable expression data than the IVT-based platform with partially degraded RNA. Next, data preprocessing procedures for the DASL-based gene expression results from postmortem frozen brain samples were systematically tested. We developed a data preprocessing pipeline to prepare this dataset for downstream analyses between autistic and control samples. Differential expression and enrichment analyses revealed that genes regulating cell cycle, apoptosis, proliferation, cellular differentiation, and neural patterning functions were dysregulated in young autistic cases. Similar results were found in an expanded analysis of autism at young and adult ages. Our observations suggest that molecular aberrancies in prenatal and early postnatal neurodevelopment may be responsible for brain overgrowth, cortical asymmetry, cortical disconnectivity, aberrant neural function, and ultimately the behavioral phenotype of autism.
机译：尽管自闭症是一种高度可遗传的神经发育障碍，在生命的早期表现出大脑过度生长，但这种异常发育的潜在遗传机制仍然未知。长期以来，人们一直认为自闭症是由于异常的细胞增殖，细胞数量调节以及随着皮层形成而发生的细胞迁移功能而在产前开始的。这些可能性从未在年轻的自闭症大脑皮层中进行过系统地检查，部分原因是组织保存质量的限制。我们旨在通过全基因组表达谱分析和RTPCR对来自年轻自闭症和对照病例的死后脑组织的mRNA进行检验。为了获得最大可能样本量的最可靠数据集，我们需要在参考库中部分降解的RNA上比较基于体外转录（IVT）和cDNA介导的基于退火选择和连接（DASL）的表达平台，并且冷冻和福尔马林固定的死后脑组织。结果表明，基于DASL的平台比具有部分降解RNA的基于IVT的平台产生更可靠的表达数据。接下来，系统地测试了死后冷冻脑样本中基于DASL的基因表达结果的数据预处理程序。我们开发了数据预处理管道，以准备此数据集，以用于自闭样本和对照样本之间的下游分析。差异表达和富集分析表明，在年轻的自闭症患者中，调控细胞周期，凋亡，增殖，细胞分化和神经模式功能的基因表达失调。在对青年和成人自闭症的扩展分析中发现了相似的结果。我们的观察表明，产前和产后早期神经发育中的分子畸变可能与脑过度生长，皮质不对称，皮质脱节，神经功能异常以及最终自闭症的行为表型有关。

著录项

  • 作者

    Chow, Maggie Lok Mun.;

  • 作者单位

    University of California, San Diego.;

  • 授予单位 University of California, San Diego.;
  • 学科 Biology Neuroscience.;Health Sciences Medicine and Surgery.;Biology Genetics.
  • 学位 Ph.D.
  • 年度 2011
  • 页码 221 p.
  • 总页数 221
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号