The Biology of Chromosome 21 Genes: towards Gene-Phenotype Correlations in Down

描述（由申请人提供）：为了在唐氏综合症研究中创造新的研究方向和新的合作机会，需要将两组研究人员聚集在一起：(1)专门研究人类21号染色体和唐氏综合征及其小鼠模型的研究人员；(2)研究21号染色体特异性基因的细胞/分子生物学或21号染色体特异性通路的研究人员，以及开发/使用可能适用于唐氏综合征研究的新方法的研究人员。第一个小组包括21号染色体专家，他们参与了21号染色体和同源小鼠基因组区域的制图、测序和注释，21号染色体和同源小鼠基因的鉴定和表达分析，唐氏综合征小鼠模型的创建和分析，包括片段三体和转基因，以及人类唐氏综合征表型的定义。第二组的研究人员没有参与唐氏综合症的研究，甚至可能没有意识到他们的工作可以影响唐氏综合症的研究。他们正在研究单个基因或家族成员，如转录因子、蛋白质修饰剂或映射到21号染色体的细胞表面受体，或通路/过程，如神经发生、细胞粘附或信号转导，每一个都有几个组成或调节基因映射到21号染色体。或者他们正在使用大规模的方法来测定蛋白质表达或数学模型来进行途径分析。

DESCRIPTION (provided by applicant): To create new research directions and opportunities for new collaborations in Down syndrome research, there is a need to bring together two groups of investigators: (1) those specifically studying human chromosome 21 and Down syndrome and its mouse models, and (2) those studying the cell/molecular biology of specific genes that map to chromosome 21 or specific pathways whose components map to chromosome 21, and those developing/using novel methodologies that might be applicable to Down syndrome research. The first group includes experts on chromosome 21 who have been involved in the mapping, sequencing, and annotation of chromosome 21 and orthologous mouse genomic regions, the identification and expression analysis of chromosome 21 and orthologous mouse genes, the creation and analysis of mouse models of Down syndrome, both segmental trisomies and transgenics, and the definition of the human Down syndrome phenotype. Investigators in the second group are not involved in Down syndrome research and may not even be aware that their work can impact Down syndrome research. They are studying individual genes or family members such as transcription factors, protein modifiers, or cell surface receptors that map to chromosome 21, or pathways/processes such as neurogenesis, cell adhesion, or signal transduction, each of which has several component or modulating genes mapping to chromosome 21. Or they are using large scale approaches to assay protein expression or mathematical modeling for pathway analysis. This application requests funding to cover venue and travel expenses for a workshop to bring together approximately 30 established chromosome 21 Down syndrome investigators with approximately 20 non-Down syndrome but chromosome 21 gene/pathway experts to discuss the biology of chromosome 21-encoded genes and the implications for their overexpression in the Down syndrome phenotype. The meeting will be held for three days in Washington, DC within a time frame of five months after the availability of funding. It is anticipated that this workshop will generate new, testable theories for gene-phenotype correlations in Down syndrome, foster new collaborations, and introduce new researchers with novel expertise to the Down syndrome research field.