Paired-End Sequence Mapping Detects Extensive Genomic Rearrangement and Translocation during Divergence of
 Francisella tularensis
 subsp.
 tularensis
 and
 Francisella tularensis
 subsp.
 holarctica
 Populations

Dempsey, Michael P.; Nietfeldt, Joseph; Hinrichs, Steven H.; Crawford, R. M. M.; Benson, Andrew K.

doi:10.1128/jb.00437-06

Cited by 26 publications

(32 citation statements)

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“…analysis (8), pulsed-field gel electrophoresis (12,29), amplified fragment length polymorphism (12,13), canonical insertiondeletions (22), and multilocus variable-number tandem repeat (VNTR) analysis (MLVA) (11,18). These subpopulations are correlated with different host and vector distributions (11,19) and may differ in virulence (29).…”

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confidence: 99%

Phylogeography of Francisella tularensis : Global Expansion of a Highly Fit Clone

et al. 2009

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Francisella tularensis contains several highly pathogenic subspecies, including Francisella tularensis subsp. holarctica, whose distribution is circumpolar in the northern hemisphere. The phylogeography of these subspecies and their subclades was examined using whole-genome single nucleotide polymorphism (SNP) analysis, high-density microarray SNP genotyping, and real-time-PCR-based canonical SNP (canSNP) assays. Almost 30,000 SNPs were identified among 13 whole genomes for phylogenetic analysis. We selected 1,655 SNPs to genotype 95 isolates on a high-density microarray platform. Finally, 23 clade-and subclade-specific canSNPs were identified and used to genotype 496 isolates to establish global geographic genetic patterns. We confirm previous findings concerning the four subspecies and two Francisella tularensis subsp. tularensis subpopulations and identify additional structure within these groups. We identify 11 subclades within F. tularensis subsp. holarctica, including a new, genetically distinct subclade that appears intermediate between Japanese F. tularensis subsp. holarctica isolates and the common F. tularensis subsp. holarctica isolates associated with the radiation event (the B radiation) wherein this subspecies spread throughout the northern hemisphere. Phylogenetic analyses suggest a North American origin for this B-radiation clade and multiple dispersal events between North America and Eurasia. These findings indicate a complex transmission history for F. tularensis subsp. holarctica.

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Phylogeography of Francisella tularensis : Global Expansion of a Highly Fit Clone

et al. 2009

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“…Genetically monomorphic pathogens may have recently passed through a population bottleneck, reducing or abolishing genetic diversity (1). Despite the considerable conservation of overall genomic content among F. tularensis subspecies, the organizations of discrete genetic elements differ (8). The observed translocations and rearrangements appear to be mediated by the movement of IS elements, most notably by the highly abundant ISFtu1 gene (27).…”

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confidence: 99%

“…Computational analysis of the different continuous regions (CRs) previously described (8) suggested that two loci, namely, CR10 and CR16, could be used to differen- tiate between F. tularensis type A and type B strains. The CR10 and CR16 primers were based on chromosomal content within these two loci that was common (C) to both SCHU S4 and LVS or specific to either SCHU S4 (S) or LVS (L).…”

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confidence: 99%

“…holarctica originated from North America and was introduced multiple times into Eurasia (15,33). Furthermore, comparative genome hybridization and sequencing were used to demonstrate a unique deletion present within an F. tularensis isolate found in an Iberian Peninsula tularemia outbreak (2,7,8).…”

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“…holarctica that were dispersed in F. tularensis subsp. tularensis using pairedend sequencing (8). A recent genomic comparison between four F. tularensis subsp.…”

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Francisella tularensis Molecular Typing Using Differential Insertion Sequence Amplification

et al. 2011

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Tularemia is a potentially fatal disease that is caused by the highly infectious and zoonotic pathogen Francisella tularensis. Despite the monomorphic nature of sequenced F. tularensis genomes, there is a significant degree of plasticity in the organization of genetic elements. The observed variability in these genomes is due primarily to the transposition of direct repeats and insertion sequence (IS) elements. Since current methods used to genotype F. tularensis are time-consuming and require extensive laboratory resources, IS elements were investigated as a means to subtype this organism. The unique spatial location of specific IS elements provided the basis for the development of a differential IS amplification (DISA) assay to detect and distinguish the more virulent F. tularensis subsp. tularensis (subtypes A.I and A.II) and subsp. holarctica (type B) strains from F. tularensis subsp. novicida and other near neighbors, including Francisella philomiragia and Francisella-like endosymbionts found in ticks. Amplicon sizes and sequences derived from DISA showed heterogeneity within members of the subtype A.I and A.II isolates but not the type B strains. These differences were due to a 312-bp fragment derived from the IS element ISFtu1. Analysis of wild-type F. tularensis isolates by DISA correlated with pulsed-field gel electrophoresis genotyping utilizing two different restriction endonucleases and provided rapid results with minimal sample processing. The applicability of this molecular typing assay for environmental studies was demonstrated by the accurate identification and differentiation of tick-borne F. tularensis. The described approach to IS targeting and amplification provides new capability for epidemiological investigations and characterizations of tularemia source outbreaks.

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Atypical mRNA fusions in PML‐RARA positive, RARA‐PML negative acute promyelocytic leukemia

Walz

Grimwade

Saußele³

et al. 2010

Genes Chromosomes & Cancer

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Reciprocal RARA-PML transcripts are not detected in approximately 25% of patients with PML-RARA positive acute promyelocytic leukemia (APL), but the reasons for this are poorly understood. We studied 21 PML-RARA positive/RARA-PML negative cases by bubble PCR and multiplex long template PCR to identify the genomic breakpoints. Additional RT-PCR analysis was performed based on the DNA findings. Three cases were found to have complex rearrangements involving a third locus: the first had a PML-CDC6-RARA forward DNA fusion and expressed a chimeric PML-CDC6-RARA mRNA in addition to a PML-RARA. The other two had HERC1-PML and NT_009714.17-PML genomic fusion sequences at their respective reciprocal breakpoints. Six patients were falsely classified as RARA-PML negative due to deletions on chromosome 15 and/or 17, or alternative splicing leading to atypical RARA-PML fusion transcripts, which were not identified by conventional RT-PCR assays. This study demonstrates that the frequency of RARA-PML expression has been underestimated and highlights remarkable complexity at chromosomal breakpoint regions in APL even in cases with an apparently simple balanced t(15;17)(q24;q12).

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Paired-End Sequence Mapping Detects Extensive Genomic Rearrangement and Translocation during Divergence of Francisella tularensis subsp. tularensis and Francisella tularensis subsp. holarctica Populations

Cited by 26 publications

References 30 publications

Phylogeography of Francisella tularensis : Global Expansion of a Highly Fit Clone

Phylogeography of Francisella tularensis : Global Expansion of a Highly Fit Clone

Francisella tularensis Molecular Typing Using Differential Insertion Sequence Amplification

Atypical mRNA fusions in PML‐RARA positive, RARA‐PML negative acute promyelocytic leukemia

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