Unknown,Transcriptomics,Genomics,Proteomics

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Widespread, focal copy number variations (CNV) in Trypanosoma cruzi strains

ABSTRACT: Trypanosoma cruzi is a protozoan parasite and the etiologic agent of Chagas disease, an important public health problem in Latin America. T. cruzi is diploid, almost exclusively asexual, and displays an extraordinarily diverse population structure both genetically and phenotypically. Yet, to date the genotypic diversity of T. cruzi and its relationship, if any, to biological diversity have not been studied at the whole genome level. In this study, we used whole genome oligonucleotide tiling arrays to compare gene content in biologically disparate T. cruzi strains by comparative genomic hybridization (CGH). We observed that T. cruzi strains display widespread and focal copy number variations (CNV) and a substantially greater level of diversity than can be adequately defined by the current genetic typing methods. As expected, CNV were particularly frequent in gene family-rich regions containing mucins and trans-sialidases but were also evident in core genes. Gene groups that showed little variation in copy numbers among the strains tested included those encoding protein kinases and ribosomal proteins, suggesting these loci were less permissive to CNV. Moreover, frequent variation in chromosome copy numbers were observed, and chromosome-specific CNV signatures were shared by genetically divergent T. cruzi strains, suggesting a greater degree of chromosome exchange than previously thought. Genomic DNA samples from 16 T. cruzi strains were compared to genomic DNA from the CL Brener strain by competitive hybridizations on whole genome oligonucleotide tiling arrays.

ORGANISM(S): Trypanosoma cruzi

SUBMITTER: Todd Minning

PROVIDER: E-GEOD-23576 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Widespread, focal copy number variations (CNV) and whole chromosome aneuploidies in Trypanosoma cruzi strains revealed by array comparative genomic hybridization.

Minning Todd A TA Weatherly D Brent DB Flibotte Stephane S Tarleton Rick L RL

BMC genomics 20110307

<h4>Background</h4>Trypanosoma cruzi is a protozoan parasite and the etiologic agent of Chagas disease, an important public health problem in Latin America. T. cruzi is diploid, almost exclusively asexual, and displays an extraordinarily diverse population structure both genetically and phenotypically. Yet, to date the genotypic diversity of T. cruzi and its relationship, if any, to biological diversity have not been studied at the whole genome level.<h4>Results</h4>In this study, we used whole ...[more]

PMID: 21385342

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Project description:Copy number variants (CNVs) reshape gene structure, modulate gene expression, and contribute to significant phenotypic variation. Previous studies have revealed CNV patterns in natural populations of Drosophila melanogaster and suggested that selection and mutational bias shape genomic patterns of CNV. While previous CNV studies focused on heterogeneous strains, here we established a number of second-chromosome substitution lines to uncover CNV characteristics when homozygous. The percentage of genes harboring CNVs is higher than found in previous studies. More CNVs are detected in homozygous than heterozygous substitution strains, suggesting the comparative genomic hybridization arrays underestimate CNV owing to heterozygous masking. We incorporated previous gene expression data collected from some of the same substitution lines to investigate relationships between CNV gene dosage and expression. Most genes present in CNVs show no evidence of increased or diminished transcription, and the fraction of such dosage-insensitive CNVs is greater in heterozygotes. More than 70% of the dosage-sensitive CNVs are recessive with undetectable effects on transcription in heterozygotes. A deficiency of singletons in recessive dosage-sensitive CNVs supports the hypothesis that most CNVs are subject to negative selection. On the other hand, relaxed purifying selection might account for the higher number of protein-protein interactions in dosage insensitive CNVs than in dosage-sensitive CNVs. Dosage-sensitive CNVs that are up-regulated and down-regulated coincide with copy number increases and decreases. Our results help clarify the relation between CNV dosage and gene expression in the D. melanogaster genome. To determine copy number variation, the genomic DNA from five homozygous and two heterozygous second chromosome substitution lines were extracted and compared to another second chromosome substitution line. Gene expression levels can be referred to at Series GSE12191 (Lemos et al. (2008) PMID:18791071).