Gardiner K
Eleanor Roosevelt Institute, University of Denver, and Department of Biochemistry and Genetics, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
J Neural Transm Suppl. 2003(67):21-37. doi: 10.1007/978-3-7091-6721-2_2.
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+/calcineurin 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.
将人类21号染色体基因组序列与小鼠16号、17号和10号染色体的同源区域进行比较注释，已鉴定出170对直系同源基因对。基于文献报道和计算推导的预测对这些基因进行功能注释，结果表明它们代表了广泛的细胞过程。唐氏综合征研究的一个目标是确定这些过程中哪些会因21号染色体基因的过表达而受到干扰，以及哪些可能因此导致唐氏综合征所特有的认知缺陷。有11个21号染色体基因被注释为与丝裂原活化蛋白激酶（MAP）途径的成分相互作用或受其影响，8个基因参与Ca2+/钙调神经磷酸酶信号传导。这两条途径对正常神经功能都至关重要，因此它们的干扰被认为可能与表型相关。我们提供的证据表明，在唐氏综合征的Ts65Dn小鼠模型中，4至6月龄时MAP激酶途径受到了干扰。由于观察到三体中21号染色体基因的过表达可能受检测方法、生物体、组织或脑区以及/或发育年龄的影响，分析变得复杂。
