Developmental staging of male murine embryonic gonad by SAGE analysis.

Developmental staging of male murine embryonic gonad by SAGE analysis.
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通过SAGE分析,雄性鼠类胚胎性腺的发育分期。

DOI:
10.1016/s1673-8527(08)60109-5
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发表时间:
2009-04
影响因子:
5.9
通讯作者:
Chan, Wai-Yee
Chan, Wai-Yee
中科院分区:
生物学2区
文献类型:
--
作者:
Lee, Tin-Lap;Li, Yunmin;Alba, Diana;Vong, Queenie P.;Wu, Shao-Ming;Baxendale, Vanessa;Rennert, Owen M.;Lau, Yun-Fai Chris;Chan, Wai-Yee

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尽管确定了关键基因,如胚胎性腺发育中不可或缺的Sry,但对该过程的染色体激活的基因组分类和鉴定仍然知之甚少。为了更好地了解性腺发育的遗传调控,我们进行了基因表达系列分析(SAGE)来分析基因和新的转录物,并分析了来自E10.5(胚胎第10.5天),E11.5,E12.5,E13.5,E15.5和E17.5的雄性胚胎性腺的平均152,000个标签。在6个性腺文库中鉴定了总共275,583个不映射到任何注释序列的非单例标签,并且47,255个标签映射到24,975个注释序列,其中987个序列未表征。利用无监督模式识别技术,我们建立了男性性腺发育的分子分期。而不是提供一个静态的描述性分析,我们开发的算法来聚类的SAGE数据,并分配SAGE标签到相应的染色体位置,这些数据显示在染色体图形格式。从E10.5到E17.5,观察到整体基因组活性显著增加。基于已建立的发育障碍小鼠模型,鉴定并验证了与发育过程相关的重要染色体区域。这些区域可能代表男性性腺发育障碍的早期诊断标志物以及潜在的治疗靶点。
Despite the identification of key genes such as Sry integral to embryonic gonadal development, the genomic classification and identification of chromosomal activation of this process is still poorly understood. To better understand the genetic regulation of gonadal development, we performed Serial Analysis of Gene Expression (SAGE) to profile the genes and novel transcripts, and an average of 152,000 tags from male embryonic gonads at E10.5 (embryonic day 10.5), E11.5, E12.5, E13.5, E15.5 and E17.5 were analyzed. A total of 275,583 non-singleton tags that do not map to any annotated sequence were identified in the six gonad libraries, and 47,255 tags were mapped to 24,975 annotated sequences, among which 987 sequences were uncharacterized. Utilizing an unsupervised pattern identification technique, we established molecular staging of male gonadal development. Rather than providing a static descriptive analysis, we developed algorithms to cluster the SAGE data and assign SAGE tags to a corresponding chromosomal position; these data are displayed in chromosome graphic format. A prominent increase in global genomic activity from E10.5 to E17.5 was observed. Important chromosomal regions related to the developmental processes were identified and validated based on established mouse models with developmental disorders. These regions may represent markers for early diagnosis for disorders of male gonad development as well as potential treatment targets.