Assembly of inflammation-related genes for pathway-focused genetic analysis.
Assembly of inflammation-related genes for pathway-focused genetic analysis.
复制标题
与炎症相关的基因组装，用于途径为中心的遗传分析。
DOI：
10.1371/journal.pone.0001035
复制
发表时间：
2007-10-17
期刊：
影响因子：
3.7
通讯作者：
Chang, Bao-Li
中科院分区：
文献类型：
--
作者：
Loza, Matthew J.;McCall, Charles E.;Li, Liwu;Isaacs, William B.;Xu, Jianfeng;Chang, Bao-Li
最近发现炎症相关基因的新变异与几种常见疾病之间的关联，强调了系统评价这些基因在疾病易感性中的必要性。考虑到许多基因参与了复杂的炎症反应，并且这些基因中的许多遗传变异具有改变这些基因的功能和表达的潜力，我们收集了一系列关键炎症相关基因，以便于识别疾病与炎症相关病因的遗传关联。我们首先回顾了炎症反应的各个阶段，包括免疫细胞的发育、危险感测、细胞流入损伤部位、免疫和非免疫细胞的激活和功能反应以及免疫反应的解决。在Inconvenity Pathway Analysis的帮助下，我们确定了17个参与一个或多个阶段的功能子通路。这种组织将大大增加检测基因-基因相互作用的机会，通过层次聚类的基因与他们的功能接近的途径。最后，作为一个应用实例，我们开发了标记单核苷酸多态性（tSNP）阵列，用于欧洲和非洲血统的人群，以捕获这些关键炎症相关基因的所有常见变体。这些tSNPs的检测已经被设计并组装到两个Affytelium ParAllele定制芯片中，每个芯片用于欧洲（12，011个SNPs）和非洲（21，542个SNPs）人群。与现有的全基因组阵列相比，这些tSNP对这些炎症相关基因的覆盖率更高，特别是在非洲人群中。这些tSNP阵列可以促进系统评估疾病易感性中的炎症途径。对于另外的应用，也可以采用其他基因分型平台。对于现有的全基因组关联数据，关键炎症相关基因和相关子途径的该列表可以促进全面的炎症途径聚焦关联分析。
Recent identifications of associations between novel variants in inflammation-related genes and several common diseases emphasize the need for systematic evaluations of these genes in disease susceptibility. Considering that many genes are involved in the complex inflammation responses and many genetic variants in these genes have the potential to alter the functions and expression of these genes, we assembled a list of key inflammation-related genes to facilitate the identification of genetic associations of diseases with an inflammation-related etiology. We first reviewed various phases of inflammation responses, including the development of immune cells, sensing of danger, influx of cells to sites of insult, activation and functional responses of immune and non-immune cells, and resolution of the immune response. Assisted by the Ingenuity Pathway Analysis, we then identified 17 functional sub-pathways that are involved in one or multiple phases. This organization would greatly increase the chance of detecting gene-gene interactions by hierarchical clustering of genes with their functional closeness in a pathway. Finally, as an example application, we have developed tagging single nucleotide polymorphism (tSNP) arrays for populations of European and African descent to capture all the common variants of these key inflammation-related genes. Assays of these tSNPs have been designed and assembled into two Affymetrix ParAllele customized chips, one each for European (12,011 SNPs) and African (21,542 SNPs) populations. These tSNPs have greater coverage for these inflammation-related genes compared to the existing genome-wide arrays, particularly in the African population. These tSNP arrays can facilitate systematic evaluation of inflammation pathways in disease susceptibility. For additional applications, other genotyping platforms could also be employed. For existing genome-wide association data, this list of key inflammation-related genes and associated subpathways can facilitate comprehensive inflammation pathway- focused association analyses.
登录
查看更多内容
影响因子：
56.9
作者：
Duerr, Richard H.;Taylor, Kent D.;Cho, Judy H.
通讯作者：
Cho, Judy H.
DOI：
10.1142/9789812701626_0044
发表时间：
2006-01-01
影响因子：
--
作者：
De Bakker, Paul I W;Graham, Robert R;Haiman, Christopher A
通讯作者：
Haiman, Christopher A
影响因子：
4.7
作者：
Forrester, JS;Bick-Forrester, J
通讯作者：
Bick-Forrester, J
影响因子：
6.4
作者：
Hedelin, Maria;Chang, Ellen T.;Balter, Katarina Augustsson
通讯作者：
Balter, Katarina Augustsson
影响因子：
5.2
作者：
Lee, YH;Harley, JB;Nath, SK
通讯作者：
Nath, SK