TY - JOUR
T1 - Development of forward genetics in Toxoplasma gondii
AU - Sibley, L. David
N1 - Funding Information:
I am extremely indebted to many members of my laboratory and to many colleagues who have contributed generously to the events described here. I am also grateful for the funding my laboratory has received over the years from the National Institutes of Health, the United States Department of Agriculture, the American Foundation for AIDS Research, the American Heart Association, Merck Research Laboratories and the Burroughs Wellcome Fund. Our approaches were often not hypothesis driven, pushed the limits of feasibility and were exceedingly overly ambitious. Only the support of unusually open-minded peer reviewers made it possible to pursue these projects.
PY - 2009/7/1
Y1 - 2009/7/1
N2 - 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.
AB - 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.
KW - Genetic mapping
KW - Phylogeny
KW - Population genetics
KW - Virulence
UR - http://www.scopus.com/inward/record.url?scp=67349184446&partnerID=8YFLogxK
U2 - 10.1016/j.ijpara.2009.02.011
DO - 10.1016/j.ijpara.2009.02.011
M3 - Review article
C2 - 19254720
AN - SCOPUS:67349184446
SN - 0020-7519
VL - 39
SP - 915
EP - 924
JO - International Journal for Parasitology
JF - International Journal for Parasitology
IS - 8
ER -