From GWAS to function: lessons from blood cells.
From GWAS to function: lessons from blood cells.
复制标题
DOI：
10.1111/voxs.12217
复制
发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Soranzo N
中科院分区：
文献类型：
--
作者：
Vasquez LJ;Mann AL;Chen L;Soranzo N
造血，或从定向祖细胞形成成熟血细胞的过程，代表了细胞分化和谱系特化的可获得和充分研究的范例。遗传关联研究为发现造血发育的新基因、生物学途径和机制提供了强有力的方法。在这里，我们强调了最近的全基因组关联研究（GWAS）的结果，将145个基因组位点与影响欧洲和其他祖先红细胞、白色细胞和血小板形成的性状联系起来。我们提出了解决GWAS发现中的主要挑战的策略，特别是寻找遗传变异的功能和调节作用，并鉴定这些遗传变异影响血液学表型的基因。我们认为，血液学性状变异的研究为理解GWAS相关变体的功能提供了一个理想的范例，这是由于细胞的可接近性，简单的细胞表型以及专注于表征影响高纯成熟细胞群中调控景观的遗传和表观遗传因素。
Haematopoiesis, or the process of formation of mature blood cells from committed progenitors, represents an accessible and well‐studied paradigm of cell differentiation and lineage specification. Genetic association studies provide a powerful approach to discover new genes, biological pathways and mechanisms underlying haematopoietic development. Here, we highlight recent findings of genomewide association studies (GWAS) linking 145 genomic loci to traits affecting the formation of red and white cells and platelets in European and other ancestries. We present strategies to address the main challenges in GWAS discoveries, particularly to find functional and regulatory effects of genetic variants, and to identify genes through which these genetic variants affect haematological phenotypes. We argue that studies of haematological trait variation provide an ideal paradigm for understanding the function of GWAS‐associated variants owing to the accessible nature of cells, simple cellular phenotype and focused efforts to characterize the genetic and epigenetic factors influencing the regulatory landscape in highly pure mature cell populations.