a statistical design for testing transgenerational genomic imprinting in natural human populations统计设计测试继代自然人类基因组印记.pdfVIP

A Statistical Design for Testing Transgenerational Genomic Imprinting in Natural Human Populations 1,2. 1. 1 3 3 4 1,4 Yao Li , Yunqian Guo , Jianxin Wang , Wei Hou , Myron N. Chang , Duanping Liao , Rongling Wu * 1 Center for Computational Biology, Beijing Forestry University, Beijing, People’s Republic of China, 2 Department of Statistics, West Virginia University, Morgantown, West Virginia, United States of America, 3 Department of Biostatistics, University of Florida, Gainesville, Florida, United States of America, 4 Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania, United States of America Abstract Genomic imprinting is a phenomenon in which the same allele is expressed differently, depending on its parental origin. Such a phenomenon, also called the parent-of-origin effect, has been recognized to play a pivotal role in embryological development and pathogenesis in many species. Here we propose a statistical design for detecting imprinted loci that control quantitative traits based on a random set of three-generation families from a natural population in humans. This design provides a pathway for characterizing the effects of imprinted genes on a complex trait or disease at different generations and testing transgenerational changes of imprinted effects. The design is integrated with population and cytogenetic principles of gene segregation and transmission from a previous generation to next. The implementation of the EM algorithm within the design framework leads to the estimation of genetic parameters that define imprinted effects. A simulation study is used to investigate