Identifizierung und Charakterisierung von Parent-of-origin Effekten beim atopischen Ekzem - Identification and functional analysis of parent-of-origin effects in eczema

湿疹母源效应的鉴定和功能分析

• 批准号: 181901646
• 负责人: Professorin Dr. Young-Ae Lee
• 金额: --
• 依托单位: Experimental and Clinical Research Center (ECRC)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/181901646?language=en
• 关键词: Identifizierung; und; Charakterisierung; von; Parent

Eczema is a common chronic inflammatory skin disease with complex etiology. Independent studies have shown that children eczema-affected mothers have a higher risk to develop the disease than children of eczema-affected fathers (parent-of-origin effect). Parent-of-origin effects may be due to genomic imprinting and/or feto-maternal interaction during pregnancy or lactation (maternal effect). We propose to study parent-of-origin effects in eczema by analyzing a set of 270 complete nuclear families with eczema in which high-density SNP data is available in our laboratory. Interestingly, in these families the frequency of eczema is much higher in the mothers than in the fathers (32% versus 18%, respectively), supporting the existence of parent-of-origin effects. We have analyzed the genotype data using the parent-of-origin likelihood ratio test (PO-LRT test) to detect of parent-of-origin and maternal effects. Importantly, our scan tends to identify genomic regions containing predicted or experimentally validated imprinted genes, supporting the validity of our approach (P < 0.05). We propose to select a set of 96 SNPs showing imprinting or maternal effects based on our PO-LRT results and to test them for replication in an independent sample of 1000 eczema families. Expression and epigenetic analyses will be performed in order to provide functional evidence of imprinting for the candidate genes identified. This will be the first study addressing parent-of-origin effects in eczema at a genome-wide level, providing novel information on this interesting aspect of the disease etiology.

湿疹是一种常见的慢性炎症性皮肤病，病因复杂。独立研究表明，患有湿疹的母亲所生的孩子比父亲患有湿疹的孩子患该病的风险更高（父母效应）。亲本效应可能是由于怀孕或哺乳期间的基因组印记和/或胎儿-母体相互作用（母体效应）。我们建议通过分析一组 270 个完整的湿疹核心家庭来研究湿疹的父母来源效应，其中我们的实验室可以获得高密度 SNP 数据。有趣的是，在这些家庭中，母亲患湿疹的频率远高于父亲（分别为 32% 和 18%），这支持了父母来源效应的存在。我们使用亲本似然比检验（PO-LRT 检验）分析了基因型数据，以检测亲本和母体效应。重要的是，我们的扫描倾向于识别包含预测或实验验证的印记基因的基因组区域，支持我们方法的有效性（P < 0.05）。我们建议根据我们的 PO-LRT 结果选择一组 96 个显示印记或母体效应的 SNP，并测试它们在 1000 个湿疹家庭的独立样本中的复制情况。将进行表达和表观遗传分析，以便为所识别的候选基因提供印记的功能证据。这将是第一项在全基因组水平上解决湿疹母体效应的研究，为该疾病病因学的这一有趣方面提供了新的信息。