A gene expression map of human chromosome 21 orthologues in the mouse
A gene expression map of human chromosome 21 orthologues in the mouse
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DOI：
10.1038/nature01178
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发表时间：
2002-12-05
期刊：
影响因子：
64.8
通讯作者：
Yaspo, ML
中科院分区：
文献类型：
--
作者：
Gitton, Y;Dahmane, N;Yaspo, ML
人类 21 号染色体 (HSA21)(1) 的 DNA 序列为其所有基因的系统分子表征开辟了途径。 21 三体与唐氏综合症有关，唐氏综合症是人类智力低下最常见的遗传原因。表型包括各种器官畸形、颅面部刻板异常和脑畸形(2)。先天性非整倍体的分子分析提出了特殊的挑战，因为非整倍体区域包含许多功能未知的蛋白质编码基因。了解其功能的一个重要步骤是分析生物体发育关键阶段的 mRNA 表达模式。在果蝇、青蛙和小鼠中进行的开创性研究表明，表达在空间和/或时间上受到限制的基因通常与特定的个体发育过程相关。在这里，我们通过胚胎和大脑发育关键阶段的大规模 mRNA 原位杂交和表达序列标签的计算机（计算）挖掘相结合，描述了小鼠 HSA21 基因直系同源物的表达谱。这种染色体规模的表达注释将许多测试的基因与潜在的生物学作用联系起来，并为唐氏综合症的发病机制提出了候选基因。
The DNA sequence of human chromosome 21 (HSA21)(1) has opened the route for a systematic molecular characterization of all of its genes. Trisomy 21 is associated with Down's syndrome, the most common genetic cause of mental retardation in humans. The phenotype includes various organ dysmorphies, stereotypic craniofacial anomalies and brain malformations(2). Molecular analysis of congenital aneuploidies poses a particular challenge because the aneuploid region contains many protein-coding genes whose function is unknown. One essential step towards understanding their function is to analyse mRNA expression patterns at key stages of organism development. Seminal works in flies, frogs and mice showed that genes whose expression is restricted spatially and/or temporally are often linked with specific ontogenic processes. Here we describe expression profiles of mouse orthologues to HSA21 genes by a combination of large-scale mRNA in situ hybridization at critical stages of embryonic and brain development and in silico (computed) mining of expressed sequence tags. This chromosome-scale expression annotation associates many of the genes tested with a potential biological role and suggests candidates for the pathogenesis of Down's syndrome.