Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Trends Genet. 2022 Feb;38(2):152-168. doi: 10.1016/j.tig.2021.09.013. Epub 2021 Nov 2.
There has been a rapid increase in human genome sequencing in the past two decades, resulting in the identification of millions of previously unknown genetic variants. However, African populations are under-represented in sequencing efforts. Additional sequencing from diverse African populations and the construction of African-specific reference genomes is needed to better characterize the full spectrum of variation in humans. However, sequencing alone is insufficient to address the molecular and cellular mechanisms underlying variable phenotypes and disease risks. Determining functional consequences of genetic variation using multi-omics approaches is a fundamental post-genomic challenge. We discuss approaches to close the knowledge gaps about African genomic diversity and review advances in African integrative genomic studies and their implications for precision medicine.
在过去的二十年中,人类基因组测序技术迅速发展,已经鉴定出了数百万个以前未知的遗传变异。然而,在测序工作中非洲人群的代表性不足。需要对来自不同非洲人群的样本进行更多的测序,并构建非洲特有的参考基因组,以便更好地描述人类变异的全貌。但是,仅仅测序不足以解决表型和疾病风险可变的分子和细胞机制。使用多组学方法确定遗传变异的功能后果是后基因组学的一个基本挑战。我们讨论了缩小有关非洲基因组多样性的知识差距的方法,并回顾了非洲综合基因组研究的进展及其对精准医学的影响。