表观基因组学作为理解表型细微差别的范例。

Cornelia Fanter, Carla B. Madelaire, D. Genereux, F. van Breukelen, D. Levesque, Allyson Hindle
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引用次数: 5

摘要

量化表型的基因组和表观基因组调节剂的相对重要性是比较生理学的一个焦点挑战,但进展受到数据和分析方法的可用性的限制。先前的研究将生理特征与编码DNA序列、调控DNA序列和表观遗传状态联系起来,但很少有研究理清它们的相对贡献,或明确区分因果效应(“驱动因素”)与相关性。进展受到几个因素的限制,包括将连续和流体表型视为离散和静态的经典方法,以及难以考虑可以调节表型的完整多样性机制,例如基因可及性,转录,mRNA加工和翻译。我们认为,关注表型的细微差别,进展到与表观遗传标记的关联,然后对表观遗传机制进行因果分析,将使进化路径得到更清晰的评估。这将成为一个重要的范式转变的基础,并为寻找基因组和表观基因组特征与生理学之间的联系提供动力。在这里,我们回顾了不断增长的基因调控机制的知识基础,并描述了它们与表型的联系,提出了解决广泛认可的挑战的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Epigenomics as a paradigm to understand the nuances of phenotypes.
Quantifying the relative importance of genomic and epigenomic modulators of phenotype is a focal challenge in comparative physiology, but progress is constrained by availability of data and analytic methods. Previous studies have linked physiological features to coding DNA sequence, regulatory DNA sequence, and epigenetic state, but few have disentangled their relative contributions or unambiguously distinguished causative effects ('drivers') from correlations. Progress has been limited by several factors, including the classical approach of treating continuous and fluid phenotypes as discrete and static across time and environment, and difficulty in considering the full diversity of mechanisms that can modulate phenotype, such as gene accessibility, transcription, mRNA processing and translation. We argue that attention to phenotype nuance, progressing to association with epigenetic marks and then causal analyses of the epigenetic mechanism, will enable clearer evaluation of the evolutionary path. This would underlie an essential paradigm shift, and power the search for links between genomic and epigenomic features and physiology. Here, we review the growing knowledge base of gene-regulatory mechanisms and describe their links to phenotype, proposing strategies to address widely recognized challenges.
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