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High recombination rates and hotspots in a Plasmodium falciparum genetic cross

Hongying Jiang1, Na Li2, Vivek Gopalan3, Martine M Zilversmit4, Sudhir Varma3, Vijayaraj Nagarajan3, Jian Li15, Jianbing Mu1, Karen Hayton1, Bruce Henschen1, Ming Yi6, Robert Stephens6, Gilean McVean7, Philip Awadalla8, Thomas E Wellems1 and Xin-zhuan Su1*

Author Affiliations

1 Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA

2 MedImmune, 1 MedImmune Way, Gaithersburg, MD 20878, USA

3 Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA

4 Charles-Bruneau Cancerology Centre, University of Montreal, Faculty of Medicine, Ste. Justine Research Centre, 3175 Chemin de Côte-Ste-Catherine, Montreal, Québec H3T 1C5, Canada

5 State Key Laboratory of Stress Cell Biology, School of Life Science, Xiamen University, 422 Siming South Road, Xiamen, Fujian 361005, PR China

6 Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, 430 Miller Drive, Frederick, MD 21702, USA

7 Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK

8 Department of Pediatrics, University of Montreal, Faculty of Medicine, Ste. Justine Research Centre, 3175 Chemin de Côte-Ste-Catherine, Montreal, Québec H3T 1C5, Canada

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Genome Biology 2011, 12:R33  doi:10.1186/gb-2011-12-4-r33

Published: 4 April 2011

Additional files

Additional file 1:

Copy number variations (segmentation means) between 7G8 and GB4 relative to 3D7.

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Additional file 2:

Inheritance patterns of markers on the P. falciparum 14 chromosomes among the 32 progeny of the 7G8 × GB4 cross. For a particular chromosomal position, the progeny (horizontal bars) inherited DNA either from 7G8 (red) or GB4 (blue). Genotypes before (upper panels) and after (lower panels) applying filters to remove probe calling noise and double crossover events (see Materials and methods). Each horizontal line represents a single progeny, and each vertical line represents a different mSFP marker. The vertical cyan/orange lines represent microsatellite positions (cyan, GB4 genotypes; orange, 7G8 genotypes), and black vertical lines indicate centromere positions.

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Additional file 3:

Genotypes, marker distances, centromere positions, and inheritance of mSFPs and 254 MSs among 32 independent recombinant progeny from the 7G8 × GB4 cross [9].

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Additional file 4:

Number and size distribution of double crossovers from the 14 chromosomes after computational filtering. Crossover sizes are the distance in kilobases between flanking markers with different genotypes.

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Additional file 5:

Recombination events and Dd2 allele frequency along each of the 14 P. falciparum chromosomes. Each panel represents one chromosome as marked (chr). Recombination events (black vertical lines) were the number of changes in inheritance pattern (parental allelic type) between two adjacent markers among 35 progeny, and Dd2 allele frequency is the proportion of Dd2 allele among the Dd2 × HB3 progeny (red curves). The arrowheads under each panel indicate the putative positions of centromeres for the 14 chromosomes according to [11]. The original data were published previously [8]. The dashed horizontal lines delimit the significant inheritance bias from 1:1 segregation.

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Additional file 6:

Genotypes, marker distances, centromere positions, and inheritance of microsatellite markers among 35 progeny from the Dd2 × HB3 cross.

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Additional file 7:

Positive correlation between the number of recombination events and chromosome sizes. The numbers within circles mark the positions of the chromosomes.

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Additional file 8:

Plots of crossover counts per meiosis per megabase sequence from the 14 P. falciparum chromosomes. (a) Total crossover counts from each chromosome were divided by 32 progeny (meiosis) and its chromosome size (marker span) in megabases and plotted. (b) Crossover counts from the right arms (right side of the centromere) of each chromosome were divided by 32 progeny (meiosis) and the size of the chromosome arm in megabases. (c) The same as (b) but using the chromosome left arms.

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Additional file 9:

Plots of coefficient coincidence against crossover distance in megabases for each of the 14 chromosomes. The grey areas represent 95% confidence intervals.

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Additional file 10:

Physical and genetic maps of the 14 P. falciparum chromosomes after removing recombination hotspots at chromosome ends. The vertical scale lines (red) on the left indicate genetic distance in centimorgans, and the one on the right (blue) is the physical distance in kilobases. Thin grey lines connect the genetic position of each marker with its mapped physical position on the chromosome. The arrowheads on the right side of the blue vertical lines indicate the putative positions of centromeres for the 14 chromosomes according to [11].

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Additional file 11:

Length, recombination rate, chromosome location, and AT content of DNA sequences in the recombination hotspots of the 7G8 × GB4 and Dd2 × HB3 genetic crosses.

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Additional file 12:

Significantly enriched Gene Ontology terms (genes) in the recombination hotspots.

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Additional file 13:

Putative motifs enriched in hotspots and their occurrence frequencies (counts/kb).

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Additional file 14:

Aligned amino acid sequences of the putative P. falciparum zinc finger protein (PFL0465c) and those of human and mouse PRDM9 proteins. Human PRDM9 was used to blast the P. falciparum genome database [16], and PFL0465c was the protein with the highest score (192) and the lowest P-value (3.0E-15). The color coded domains are: yellow, P. falciparum zinc fingers; green, human PRDM9 zinc fingers; grey, KRAB box; cyan, SET domain; purple, putative eukaryotic DNA topoisomerase I DNA binding domain. The domains/motifs were identified using GenomeNet Motif Search [42].

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