Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
Am J Phys Anthropol. 2020 May;171 Suppl 70:174-194. doi: 10.1002/ajpa.24051. Epub 2020 Mar 27.
Primates display a wide range of phenotypic variation underlaid by complex genetically regulated mechanisms. The links among DNA sequence, gene function, and phenotype have been of interest from an evolutionary perspective, to understand functional genome evolution and its phenotypic consequences, and from a biomedical perspective to understand the shared and human-specific roots of health and disease. Progress in methods for characterizing genetic, transcriptomic, and DNA methylation (DNAm) variation is driving the rapid development of extensive omics resources, which are now increasingly available from humans as well as a growing number of nonhuman primates (NHPs). The fast growth of large-scale genomic data is driving the emergence of integrated tools and databases, thus facilitating studies of gene functionality across primates. This review describes NHP genomic resources that can aid in exploration of how genes shape primate phenotypes. It focuses on the gene expression trajectories across development in different tissues, the identification of functional genetic variation (including variants deleterious for protein function and regulatory variants modulating gene expression), and DNAm profiles as an emerging tool to understand the process of aging. These resources enable comparative functional genomics approaches to identify species-specific and primate-shared gene functionalities associated with health and development.
灵长类动物表现出广泛的表型变异,这些变异是由复杂的基因调控机制所决定的。从进化的角度来看,DNA 序列、基因功能和表型之间的联系一直引起人们的兴趣,这有助于了解功能基因组的进化及其表型后果,从生物医学的角度来看,这有助于了解健康和疾病的共享和人类特有的根源。用于描述遗传、转录组和 DNA 甲基化 (DNAm) 变异的方法的进展推动了广泛的组学资源的快速发展,这些资源现在不仅可以从人类中获得,而且可以从越来越多的非人类灵长类动物 (NHPs) 中获得。大规模基因组数据的快速增长推动了集成工具和数据库的出现,从而促进了跨灵长类动物的基因功能研究。这篇综述描述了灵长类动物基因组资源,可以帮助探索基因如何塑造灵长类动物的表型。它侧重于不同组织中发育过程中的基因表达轨迹、功能遗传变异的鉴定(包括对蛋白质功能有害的变异和调节基因表达的调控变异),以及作为了解衰老过程的新兴工具的 DNAm 图谱。这些资源使比较功能基因组学方法能够识别与健康和发育相关的物种特异性和灵长类动物共享的基因功能。