Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Int J Parasitol. 2009 Jul 1;39(8):915-24. doi: 10.1016/j.ijpara.2009.02.011. Epub 2009 Feb 28.
The development of forward genetics as a functional system in Toxoplasma gondii spanned more than three decades from the mid-1970s until now. The initial demonstration of experimental genetics relied on chemically induced drug-resistant mutants that were crossed by co-infecting cats, collecting oocysts, sporulating and hatching progeny in vitro. To capitalise on this, genetic markers were employed to develop linkage maps by tracking inheritance through experimental crosses. In all, three generations of genetic maps were developed to define the chromosomes, estimate recombination rates and provide a system for linkage analysis. Ultimately this genetic map would become the foundation for the assembly of the T. gondii genome, which was derived from whole genome shotgun sequencing, into a chromosome-centric view. Finally, application of forward genetics to multigenic biological traits showed the potential to map and identify specific genes that control complex phenotypes including virulence.
弓形虫正向遗传学作为一种功能系统的发展跨越了三十多年,从 20 世纪 70 年代中期到现在。最初的实验遗传学证明依赖于化学诱导的药物抗性突变体,这些突变体通过共同感染猫、收集卵囊、体外孢子形成和孵化后代来交叉。为了充分利用这一点,遗传标记被用来通过跟踪实验杂交的遗传来开发连锁图谱。总共开发了三代遗传图谱来定义染色体、估计重组率,并为连锁分析提供系统。最终,这个遗传图谱将成为组装弓形虫基因组的基础,该基因组源自全基因组鸟枪法测序,形成以染色体为中心的视图。最后,正向遗传学在多基因生物性状中的应用表明了对控制复杂表型(包括毒力)的特定基因进行定位和鉴定的潜力。