Trisomy 21, the presence of a supernumerary chromosome 21, results in a collection of clinical features commonly known as Down syndrome (DS). DS is among the most genetically complex of the conditions that are compatible with human survival post-term, and the most frequent survivable autosomal aneuploidy. Mouse models of DS, involving trisomy of all or part of human chromosome 21 or orthologous mouse genomic regions, are providing valuable insights into the contribution of triplicated genes or groups of genes to the many clinical manifestations in DS. This endeavour is challenging, as there are >200 protein-coding genes on chromosome 21 and they can have direct and indirect effects on homeostasis in cells, tissues, organs and systems. Although this complexity poses formidable challenges to understanding the underlying molecular basis for each of the many clinical features of DS, it also provides opportunities for improving understanding of genetic mechanisms underlying the development and function of many cell types, tissues, organs and systems. Since the first description of trisomy 21, we have learned much about intellectual disability and genetic risk factors for congenital heart disease. The lower occurrence of solid tumours in individuals with DS supports the identification of chromosome 21 genes that protect against cancer when overexpressed. The universal occurrence of the histopathology of Alzheimer disease and the high prevalence of dementia in DS are providing insights into the pathology and treatment of Alzheimer disease. Clinical trials to ameliorate intellectual disability in DS signal a new era in which therapeutic interventions based on knowledge of the molecular pathophysiology of DS can now be explored; these efforts provide reasonable hope for the future.

中文翻译：

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唐氏综合症。

21 三体，即多余 21 号染色体的存在，会导致一系列临床特征，通常称为唐氏综合症 (DS)。DS 是与人类足月后生存相容的遗传最复杂的疾病之一，也是最常见的可存活常染色体非整倍体。DS 小鼠模型涉及人类 21 号染色体全部或部分三体性或直系同源小鼠基因组区域，为了解三重基因或基因组对 DS 多种临床表现的贡献提供了宝贵的见解。这项工作具有挑战性，因为 21 号染色体上有超过 200 个蛋白质编码基因，它们可以对细胞、组织、器官和系统的稳态产生直接和间接的影响。尽管这种复杂性对理解 DS 众多临床特征的分子基础提出了巨大的挑战，但它也为加深对许多细胞类型、组织、器官和系统的发育和功能的遗传机制的理解提供了机会。自从首次描述 21 三体症以来，我们对智力障碍和先天性心脏病的遗传风险因素有了很多了解。DS 患者实体瘤发生率较低，这支持了 21 号染色体基因的鉴定，该基因在过度表达时可以预防癌症。阿尔茨海默病组织病理学的普遍发生和 DS 中痴呆的高患病率为阿尔茨海默病的病理学和治疗提供了见解。改善 DS 智力障碍的临床试验标志着一个新时代的到来，现在可以探索基于 DS 分子病理生理学知识的治疗干预措施；这些努力为未来带来了合理的希望。