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

描述(申请人提供)：为了创造唐氏综合症研究的新研究方向和新的合作机会，需要召集两组研究人员：(1)专门研究人类21号染色体和唐氏综合症及其小鼠模型的研究人员，(2)研究定位于21号染色体的特定基因或其成分映射到21号染色体的特定途径的细胞/分子生物学的研究人员，以及开发/使用可能适用于唐氏综合症研究的新方法的研究人员。第一个小组包括21号染色体方面的专家，他们参与了21号染色体和直系小鼠基因组区域的绘制、测序和注释，21号染色体和直系小鼠基因的鉴定和表达分析，唐氏综合症小鼠模型的创建和分析，节段性三体和转基因，以及人类唐氏综合症表型的定义。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能会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，如映射到21号染色体的转录因子、蛋白质修饰物或细胞表面受体，或神经发生、细胞黏附或信号转导等途径/过程，其中每一个都有几个映射到21号染色体的成分或调节基因。或者他们正在使用大规模的方法来分析蛋白质表达或建立数学模型来进行途径分析。 这项申请申请资金用于支付研讨会的场地和旅费，该研讨会聚集了大约30名21号染色体唐氏综合症研究人员和大约20名非唐氏综合症但21号染色体基因/途径专家，讨论21号染色体编码基因的生物学及其在唐氏综合症表型中过度表达的含义。会议将在获得资金后的五个月内在华盛顿特区举行，为期三天。预计这次研讨会将为唐氏综合症的基因-表型相关性产生新的、可检验的理论，促进新的合作，并将具有新专业知识的新研究人员引入唐氏综合症研究领域。

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.