An Integrated Framework of Epigenomics and Human Disease

描述（由申请人提供）：人类基因组测序提供了一个“后基因组”框架，以识别遗传和表观遗传变异，并发现它们在人类疾病，特别是复杂疾病中的作用。我们将通过结合基因组序列和群体遗传变异的知识，使用综合方法研究表观遗传现象。研究基因组内的表观遗传模式将为我们对基因组组织和功能的理解提供有价值的见解。对已知印迹区域的重点研究也可能揭示可能涉及表观遗传修饰的新序列特征。从这些调查中收集到的信息可能导致基于生物学的复杂人类疾病假设，这些疾病是由于异常的表观遗传变化。影响我们大部分人口的大多数常见人类疾病，包括心血管、代谢和神经系统疾病，以及癌症等，病因复杂，涉及多种遗传、文化和/或环境因素的相互作用，以及表观遗传效应。拟议研究计划的目标是开发统计和计算工具，整合定量科学和生物科学的相关知识，以帮助研究常见复杂疾病的遗传基础。综合生物信息学和遗传流行病学以及表观遗传学模型的分析方法的综合研究范式可能是理解复杂疾病病因学基础的更有力的方法。

DESCRIPTION (provided by applicant): The sequencing of the human genome provides a 'post-genomic' framework to identify genetic and epigenetic variations and discover the role they play in human diseases, in particular complex diseases. We will investigate epigenetic phenomena using an integrated approach by combining knowledge from genomic sequences and population genetic variations. Studying the epigenetic patterns within the genome will provide valuable insight into our understanding of genome organization and function. Focused investigation of known imprinted regions may also reveal novel sequence signatures that may be involved in epigenetic modifications. The information gleaned from these investigations may lead to biologically grounded hypotheses of complex human diseases that are due to aberrant epigenetic changes. The majority of common human diseases affecting a large segment of our population, including cardiovascular, metabolic, and neurological disorders, as well as cancer among others, are complex in etiology and involve interaction of multiple genetic, cultural, and/or environmental factors, as well as epigenetic effects. The goal of the proposed research plan is to develop statistical and computational tools that integrate related knowledge from the quantitative and biological sciences to aid in the study of the genetic basis of common complex diseases. An integrated research paradigm that synthesizes analytical approaches from bioinformatics and genetic epidemiology as well as epigenetic models is likely to be a more powerful approach for understanding the etiological basis of complex diseases.