Predicting pathway perturbations in Down syndrome.
Predicting pathway perturbations in Down syndrome.
复制标题
预测唐氏综合症的通路扰动。
DOI：
10.1007/978-3-7091-6721-2_2
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Gardiner,K
中科院分区：
文献类型：
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作者：
Gardiner,K
人类21号染色体基因组序列与小鼠16、17和10号染色体同源区域的比较注释已鉴定出170个同源基因对。基于文献报道和计算得出的预测，对这些基因的功能注释表明，这些基因代表了广泛的细胞过程。唐氏综合症研究的一个目标是确定这些过程中的哪些过程受到21号染色体基因过度表达的干扰，从而可能导致唐氏综合症的认知缺陷。11个21号染色体基因被注释为与MAP激酶途径的组成部分相互作用或受其影响，8个基因参与钙/钙调神经磷酸酶信号转导。这两条通路对于正常的神经功能都是至关重要的，因此它们的干扰被认为是表型相关性的候选。我们提出的证据表明，在4-6个月大的唐氏综合征Ts65Dn小鼠模型中，MAP激酶通路受到干扰。观察到21号染色体基因在三体中的过度表达可能受到检测方法、生物、组织或脑区域和/或发育年龄的影响，这使得分析变得复杂。
Comparative annotation of human chromosome 21 genomic sequence with homologous regions of mouse chromosomes 16, 17 and 10 has identified 170 orthologous gene pairs. Functional annotation of these genes, based on literature reports and computationally-derived predictions, shows that a broad range of cellular processes are represented. A goal of Down syndrome research is to determine which of these processes are perturbed by overexpression of chromosome 21 genes, and which may, therefore, contribute to the cognitive deficits that characterize Down syndrome. Eleven chromosome 21 genes are annotated to interact with or be affected by components of the MAP Kinase pathway and eight are involved in Ca2+/ca1cineurin signaling. Both pathways are critical for normal neurological function, and consequently their perturbations are proposed as candidates for phenotypic relevance. We present evidence suggesting that the MAP Kinase pathway is perturbed in the Ts65Dn mouse model of Down syndrome at 4-6 months of age. Analysis is complicated by the observation that overexpression of chromosome 21 genes in trisomy may be affected by method of detection, organism, tissue or brain region, and/or developmental age.