Plasmodium falciparum genetic crosses
This community project was established to determine the genome sequence of the parents and progeny of the 3D7xHB3, HB3xDD2 and GB4x7G8 crosses by next generation sequencing.
Discovering the genetic causes of natural phenotypic variation in P. falciparum requires a combination of epidemiological and laboratory-based approaches. A powerful laboratory approach, which was instrumental in discovering the chloroquine resistance gene PfCRT, is to perform a genetic cross between two parasite strains with different phenotypic characteristics and to make a detailed examination of the progeny.
Unfortunately it is extremely laborious to perform genetic crosses for P. falciparum, and to date it has been accomplished only three times. The strains that have been crossed are 3D7 with HB3 (Walliker et al, 1987), HB3 with DD2 (Wellems et al, 1990) and GB4 with 7G8 (Hayton et al, 2008). The parents and progeny of these genetic crosses represent a hugely valuable resource for the malaria research community to investigate a range of different phenotypes.
Assembling an accurate P. falciparum genome sequence from short sequence reads presents many analytical challenges, particularly in regions of the genome that are highly polymorphic or made up of repetitive elements. Thus a major area of work within this project is to develop novel statistical and informatics methods for accurate genome assembly.
Data resources for MalariaGEN partners:
- Genotype data, release 0.1 - download VCF files containing genotype calls for the genetic crosses
- National Institutes of Health, USA (Tom Wellems, Karen Hayton, Xin-Zhuan Su)
- University of Notre Dame, USA (Mike Ferdig, John Tan)
- University of Glasgow, UK (Lisa Ranford-Cartwright, Jonathan Mwangi)
- HB3 x 3D7 cross. Walliker D, Quakyi IA, Wellems TE, McCutchan TF, Szarfman A, London WT, Corcoran LM, Burkot TR, Carter R (1987) Science 236:1661-6. PMID 3299700
- HB3 x DD2 cross. Wellems TE, Panton LJ, Gluzman IY, do Rosario VE, Gwadz RW, Walker-Jonah A, Krogstad DJ (1990) Nature 345:253-5. PMID 1970614
- GB4 x 7G8 cross. Hayton K, Gaur D, Liu A, Takahashi J, Henschen B, Singh S, Lambert L, Furuya T, Bouttenot R, Doll M, Nawaz F, Mu J, Jiang L, Miller LH, Wellems TE (2008) Cell Host Microbe 4:40-51. PMID: 18621009