Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nat Rev Genet. 2011 Apr;12(4):266-75. doi: 10.1038/nrg2951. Epub 2011 Mar 9.
Human genetic studies have revealed the molecular basis of countless monogenic diseases but have been less successful in associating phenotype to genotype in complex multigenic conditions. Pluripotent stem cells (PSCs), which can differentiate into any cell type, offer promise for defining the functional effects of genetic variation. Here, we recount the advantages and practical limitations of coupling PSCs to genome-wide analyses to probe complex genetics and discuss the ability to investigate epigenetic contributions to disease states. We also describe new ways of using mice and mouse embryonic stem cells (ESCs) in tandem with human stem cells to further define genotype-phenotype relationships.
人类遗传学研究已经揭示了无数单基因疾病的分子基础，但在将表型与复杂多基因条件下的基因型相关联方面做得较少成功。多能干细胞（PSCs）可以分化为任何细胞类型，为定义遗传变异的功能影响提供了希望。在这里，我们回顾了将 PSCs 与全基因组分析相结合以探究复杂遗传学的优势和实际限制，并讨论了研究疾病状态中表观遗传贡献的能力。我们还描述了使用小鼠和小鼠胚胎干细胞（ESCs）与人类干细胞相结合的新方法，以进一步定义基因型-表型关系。
