Sivasubbu Sridhar, Sachidanandan Chetana, Scaria Vinod
Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi 110 007, India.
J Genet. 2013 Dec;92(3):695-701. doi: 10.1007/s12041-013-0313-4.
Genomics research in recent years, especially the human ENCODE project, have made great strides in understanding the genomic and epigenomic structure and organization of humans. These advances promise a new era of precision medicine, through a better understanding of the genomic correlates of human physiology and promise to offer precise and personalized preventive and therapeutic options. The translation of genome-scale maps of genomic and epigenomic markers to clinically relevant information and further to medical practice await functional validation of the genomic features identified through these large-scale efforts. Such studies must essentially be done in model systems where it is possible to model physiological and pathological processes and enquire how they could be modulated by genomic elements and epigenomic signatures. The availability of large number of personal genomes and maps of genomic variations at population scale has created an acute necessity for model systems to model phenotypic and molecular effects of variations, especially in regulatory regions. Efforts to create orthologous maps have been underway in other model systems including Caenorhabditis elegans and Drosophila through the modENCODE programe and in Mus musculus through the mouse ENCODE. We propose that the enormous wealth of disease models and excellent tools to engineer genomes in zebrafish could be effectively capitalized towards making it an effective and widely used model system for precision medicine. This would be possible only through a concerted and systematic effort to create orthologous genomic and epigenomic maps for zebrafish.We discuss how the present understanding and genome-scale methodologies available in this model organism could be effectively used towards realizing this goal.
近年来的基因组学研究,尤其是人类ENCODE计划,在理解人类基因组和表观基因组结构及组织方面取得了巨大进展。这些进展预示着精准医学的新时代,通过更好地理解人类生理学的基因组关联,并有望提供精确且个性化的预防和治疗方案。将基因组和表观基因组标记的全基因组图谱转化为临床相关信息并进一步应用于医学实践,尚需对通过这些大规模研究确定的基因组特征进行功能验证。此类研究本质上必须在模型系统中进行,在该系统中可以模拟生理和病理过程,并探究它们如何受到基因组元件和表观基因组特征的调控。在群体规模上大量个人基因组和基因组变异图谱的可得性,使得建立模型系统以模拟变异的表型和分子效应变得极为必要,尤其是在调控区域。通过modENCODE计划,在包括秀丽隐杆线虫和果蝇在内的其他模型系统中,以及通过小鼠ENCODE计划在小家鼠中,都在努力创建直系同源图谱。我们认为,斑马鱼中丰富的疾病模型和出色的基因组工程工具可以得到有效利用,使其成为精准医学中一个有效且广泛应用的模型系统。只有通过协同和系统的努力为斑马鱼创建直系同源的基因组和表观基因组图谱,这才有可能实现。我们将讨论如何有效利用该模式生物目前的认识和全基因组方法来实现这一目标。