...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Congenital diaphragmatic hernia candidate genes derived from embryonic transcriptomes
【24h】

Congenital diaphragmatic hernia candidate genes derived from embryonic transcriptomes

机译：来自胚胎转录组的先天性diaphragm疝候选基因

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

Congenital diaphragmatic hernia (CDH) is a common (1 in 3,000 live births) major congenital malformation that results in significant morbidity and mortality. The discovery of CDH loci using standard genetic approaches has been hindered by its genetic heterogeneity. We hypothesized that gene expression profiling of developing embryonic diaphragms would help identify genes likely to be associated with diaphragm defects. We generated a time series of whole-transcriptome expression profiles from laser captured embryonic mouse diaphragms at embryonic day (E)11.5 and E12.5 when experimental perturbations lead to CDH phenotypes, and E16.5 when the diaphragm is fully formed. Gene sets defining biologically relevant pathways and temporal expression trends were identified by using a series of bioinformatic algorithms. These developmental sets were then compared with a manually curated list of genes previously shown to cause diaphragm defects in humans and in mouse models. Our integrative filtering strategy identified 27 candidates for CDH. We examined the diaphragms of knockout mice for one of the candidate genes, pre-B-cell leukemia transcription factor 1 (Pbx1), and identified a range of previously undetected diaphragmatic defects. Our study demonstrates the utility of genetic characterization of normal development as an integral part of a disease gene identification and prioritization strategy for CDH, an approach that can be extended to other diseases and developmental anomalies.
机译：先天性diaphragm肌疝（CDH）是常见的先天性畸形（每3,000例活产中有1例），导致严重的发病率和死亡率。使用标准遗传方法发现CDH基因座已受到其遗传异质性的阻碍。我们假设发育中的胚胎diaphragm肌的基因表达谱分析将有助于鉴定可能与diaphragm肌缺陷相关的基因。当实验扰动导致CDH表型时，在胚胎天（E）11.5和E12.5，我们从激光捕获的胚胎小鼠隔膜产生了一个完整的转录组表达谱的时间序列，当隔膜完全形成时，E16.5。通过使用一系列生物信息学算法，确定了定义生物学相关途径和时间表达趋势的基因集。然后将这些发育集与手动显示的一系列基因进行比较，这些基因先前显示会在人类和小鼠模型中引起隔膜缺陷。我们的综合过滤策略确定了27个CDH候选人。我们检查了基因敲除小鼠的candidate肌中的候选基因之一，即前B细胞白血病转录因子1（Pbx1），并确定了一系列先前未发现的defects肌缺陷。我们的研究表明，正常发育的遗传特征作为疾病基因识别和CDH优先策略不可或缺的一部分，该方法可以扩展到其他疾病和发育异常。

著录项

  • 来源
  • 作者

    Meaghan K. Russell; Mauro Longoni; Julie Wells; Faouzi I. Maalouf; Adam A. Tracy; Maria Loscertales; Kate G. Ackerman; Barbara R. Pober; Kasper Lage; Carol J. Bult; Patricia K. Donahoe;

  • 作者单位

    Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114;

    Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114;

    The Jackson Laboratory, Bar Harbor, ME 04609;

    Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114;

    Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114;

    Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114;

    Departments of Pediatrics and Biomedical Genetics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642;

    Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114,Children's Hospital Boston, Boston, MA 02115,Departments of Pediatrics , Harvard Medical School, Boston, MA 02115;

    Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114,Departments of 'Surgery , Harvard Medical School, Boston, MA 02115,Broad Institute, Cambridge, MA 02142,Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Lyngby, Denmark,Center for Protein Research, University of Copenhagen, DK-2200 Copenhagen, Denmark;

    The Jackson Laboratory, Bar Harbor, ME 04609;

    Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114,Departments of 'Surgery , Harvard Medical School, Boston, MA 02115,Broad Institute, Cambridge, MA 02142;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    pleuroperitoneal folds; expression profiling; diaphragm development;

    机译：腹膜腹膜褶;表达分析隔膜发育;

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