IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
FEBS Lett. 2014 Aug 1;588(15):2415-21. doi: 10.1016/j.febslet.2014.06.032. Epub 2014 Jun 17.
Some organisms such as yeast or males of social insects are haploid, i.e. they carry a single set of chromosomes, while haploidy in mammals is exclusively restricted to mature germ cells. A single copy of the genome provides the basis for genetic analyses where any recessive mutation of essential genes will show a clear phenotype due to the absence of a second gene copy. Most prominently, haploidy in yeast has been utilized for recessive genetic screens that have markedly contributed to our understanding of development, basic physiology, and disease. Somatic mammalian cells carry two copies of chromosomes (diploidy) that obscure genetic analysis. Near haploid human leukemic cells however have been developed as a high throughput screening tool. Although deemed impossible, we and others have generated mammalian haploid embryonic stem cells from parthenogenetic mouse embryos. Haploid stem cells open the possibility of combining the power of a haploid genome with pluripotency of embryonic stem cells to uncover fundamental biological processes in defined cell types at a genomic scale. Haploid genetics has thus become a powerful alternative to RNAi or CRISPR based screens.
有些生物，如酵母或社会性昆虫的雄性，是单倍体的，即它们只携带一套染色体，而哺乳动物的单倍体仅局限于成熟的生殖细胞。基因组的单一拷贝为遗传分析提供了基础，任何必需基因的隐性突变由于缺乏第二个基因拷贝，都会表现出明显的表型。在酵母中单倍体的应用尤为突出，它被用于隐性遗传筛选，这对我们理解发育、基础生理学和疾病做出了重要贡献。体细胞哺乳动物细胞携带两套染色体（二倍体），这使得遗传分析变得复杂。然而，已经开发出了近单倍体人类白血病细胞作为高通量筛选工具。尽管被认为不可能，但我们和其他人已经从孤雌生殖的小鼠胚胎中生成了哺乳动物单倍体胚胎干细胞。单倍体干细胞开辟了一种可能性，即将单倍体基因组的强大功能与胚胎干细胞的多能性相结合，以在基因组范围内研究特定细胞类型中的基本生物学过程。因此，单倍体遗传学已成为 RNAi 或 CRISPR 为基础的筛选的有力替代方法。
