Open Access Research article

The landscape of inherited and de novo copy number variants in a plasmodium falciparum genetic cross

Upeka Samarakoon1, Joseph M Gonzales13, Jigar J Patel12, Asako Tan1, Lisa Checkley1 and Michael T Ferdig1*

Author Affiliations

1 Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556, USA

2 Roche NimbleGen, Inc., 500 S Rosa Rd, Madison, WI 53719, USA

3 Illumina, Inc., 9885 Towne Centre Drive, San Diego, CA 92121, USA

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BMC Genomics 2011, 12:457  doi:10.1186/1471-2164-12-457

Published: 22 September 2011

Additional files

Additional file 1:

Catalogue of CNVs in the HB3 × Dd2 genetic cross.

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Additional file 2:

Known chromosomal polymorphisms detected by CGH in HB3 and Dd2.

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Additional file 3:

Loss and gain frequency of CNVs across the progeny. In general the progeny population shows an accumulation of gains than losses (average gain = 14, average loss = 11). 69% of the progeny have more gains than losses.

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Additional file 4:

Hybridization signal distribution in segregating and de novo amplifications. The distribution of the log2ratio of the progeny hybridization signals at segregating and de novo CNV regions were assessed in comparison with that of the parental signal (Dd2/HB3). The positively skewed signal distribution highlights duplicated CNV regions. The clear absence of skewed signal in the Dd2/HB3 parental hybridization compared to that of the positively skewed signal distribution in progeny enabled the identification of de novo amplifications.

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Additional file 5:

Hybridization signal distribution in segregating and de novo deletions. The distribution of the log2ratio of the progeny hybridization signals at segregating and de novo CNV regions were assessed in comparison with the parental signal (Dd2/HB3). The negatively skewed signal distribution highlights deleted CNV regions. The clear absence of skewed signal in the Dd2/HB3 parental hybridization compared to that of the negatively skewed signal distribution in the progeny enabled the identification of de novo deletions.

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Additional file 6:

Size distribution of segregating and de novo CNVs. The size distribution of the CNVs was assessed as a percentage of total CNVs in each category. De novo CNVs were predominantly < 10 kb (76%), while segregating CNVs were > 10 kb (55%). In both segregating and de novo CNVs, a small percentage of CNVs were > 100 kb (segregating = 4%, de novo = 2%).

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Additional file 7:

Gene enrichment within categories of CNVs.

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Additional file 8:

Hotspots of CNV breakpoints.

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Additional file 9:

Genetic linkage in selected CNV regions. The relationship between linkage position and genome location was assessed by QTL mapping, using relative hybridization signal per probe in segregating CNV regions as a phenotype. Each individual probe signal of segregating CNVs mapped to its closest MS marker in the published linkage map for the HB3 × Dd2 genetic cross [65], highlighting the colinearity of the linkage and physical genome at the CNV regions. The pattern remained true for progeny wide inheritance of A) amplified regions (e.g. Chr 5, boxed in red) as well as, B) deleted regions (e.g. Chr 2, boxed in red).

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Additional file 10:

Allele distribution in segregating CNV regions. We directly examined the parental MS inheritance using the published linkage map for the HB3 × Dd2 genetic cross [65] overlapping the regions of segregating CNVs, in each progeny. (A) The expected number of CNVs was compared to the observed parental allele of the CNV region. We found no evidence for divergence from Mendelian expectation (chi square test, p = 0.99). A few CNVs (e.g. i-v) deviated from this expectation due to lack of marker coverage adjacent to the CNV locus and/or complexity of CNV region in parents or progeny, including two regions that has been previously known to display skewed [53] or complex allele distributions: B) single progeny with a complex CNV overlapping a segregating CNV region (A-ii) and C) complex CNV region in parent genomes (A-iv). Selected CNVs are shown by grey boxes within heat maps (Dd2 parent in column 1) and are highlighted by scatter plots.

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Additional file 11:

Allele distribution in recurrent de novo CNVs. We directly examined the parental MS inheritance [53] adjacent/overlapping the recurrent de novo CNVs in progeny. (A) Curiously, most CNVs were observed to carry one parental allele in progeny with the CNV. CNVs which were widely recurrent (> 5 progeny) were investigated closely and were discovered to be: (B) segregating regions (boxed in red) within which one of more progeny exhibited overlapping de novo CNV (boxed in gray) and/or (C) segregating complex regions (one or more CNVs in one or both parents). Selected CNVs are shown in boxed regions in the heat maps (Dd2 parent in column 1) and highlighted by the scatter plots.

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Additional file 12:

Recurrent de novo CNV in a multiallelic region. We directly examined the parental SNP allele inheritance [69] within a recurrent de novo CNV in Chr 12 in the progeny clone 7C126. The de novo CNV region is demarcated by an arrow (A) scatter plot of parent CNV profile, Dd2 parent is compared with HB3 parent; (B) scatter plot of progeny CNV profile, progeny is compared with HB3 parent. (C) SNP map of Chr 12 [69]. Each bar of the SNP map denotes a single SNP allele demarcated by the parent allele. The parent allele is highlighted by red (Dd2) and green (HB3). The SNP allele profile which overlaps the de novo CNV region confirms a HB3 allelic region interspersed within a larger Dd2 allelic region (highlighted by arrow), suggesting a potential gene conversion or double crossover.

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Additional file 13:

De novo CNV genes that overlap with CNVs in laboratory and culture adapted field isolates.

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Additional file 14:

Impact of CNVs on gene expression. A previously generated data set of gene expression at 18 hrs in the HB3 × Dd2 progeny population [74] was assessed for impact of CNVs on gene expression. All categories of CNVs resulted in an impact on the gene expression when compared with the gene expression of progeny that do not show CNV in the respective regions.

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