DETECTING PARENT-OF-ORIGIN EFFECTS FROM PEDIGREE DATA

从谱系数据中检测父母的影响

• 批准号: 7600998
• 负责人: Sanjay Shete
• 金额: $ 0.1万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7600998
• 关键词: Beckwith-Wiedemann Syndrome; Code; Computer Retrieval of Information on Scientific Projects Database; Data; Disease; Funding; Genes; Grant; Human; Institution; Methods; Modeling; Numbers; Paper; Parents; Penetrance; Research; Research Personnel; Resources; Role; Scheme; Source; Specific qualifier value; Syndrome; Testing; United States National Institutes of Health; base; genetic linkage analysis; genetic pedigree; human disease; imprint; proband; simulation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The parent-of-origin phenomenon in humans is now well recognized, and the deregulation of imprinted genes has been implicated in a number of human diseases. Recently, several linkage analysis methods have been developed to allow for parent-of-origin effects in the analysis of pedigree data. However, in general, one does not know a priori if disease-causing loci are imprinted or not. Linkage methods that allow for imprinting can lose power if there is no imprinting. Conversely, linkage methods that do not allow for imprinting will lose power if there is imprinting because of penetrance values not being correctly specified. Therefore, it is important to know whether imprinting is a possible mode of disease inheritance before performing linkage analyses. In this paper, we describe a simple covariate-coding scheme to test for the presence of parent-of-origin effects and provide a formula for calculating parent-specific penetrance values prior to any linkage analysis. In simulation studies, our coding scheme successfully detected parent-of-origin effects and, when pedigrees were ascertained sequentially or through a single proband, inclusion of this covariate more accurately estimated penetrance values than when such a covariate was not included. The use of accurate penetrance values in a linkage analysis that allows for imprinting can provide higher power when the disease locus is imprinted. Finally, we applied our approach to 27 Beckwith-Wiedemann syndrome (BWS) pedigrees, an overgrowth syndrome, and found that a maternally expressed parent-of-origin model based on the likelihood ratio test is the most parsimonious, suggesting a role for paternally imprinted genes in BWS.

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