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Jacqueline Inwald

Publications and source records attributed to Jacqueline Inwald.

7 recordsLinked to original sources
PubMed2005

Ecotypes of the Mycobacterium tuberculosis complex.

A phylogeny of the Mycobacterium tuberculosis complex has recently shown that the animal-adapted strains are found in a single lineage marked by the deletion of chromosomal region 9 (RD9) [Brosch et al., 2002. A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc. Natl Acad. Sci. USA 99 (6), 3684-3689]. We have obtained the spoligotype patterns of the RD9 deleted strains used to generate this new evolutionary scenario and we show that the presence of spoligotype spacers 3, 9, 16, 39, and 40-43 is phylogenetically informative in this lineage. We have used the phylogenetically informative spoligotype spacers to screen a database of spoligotype patterns and have identified further members of a group of strains apparently host-adapted to antelopes. The presence of the spoligotype spacers is congruent with the phylogeny generated by chromosomal deletions, suggesting that recombination is rare or absent between strains of this lineage. The phylogenetically informative spacers, in concert with the previously identified single nucleotide mutations and chromosomal deletions, can be used to identify a series of clades in the RD9 deleted lineage each with a separate host preference. Finally, we discuss the application of the ecotype concept to this series of clades and suggest that the M. tuberculosis complex may best be described as a series of host-adapted ecotypes.

Animals↗
PubMed2004

Advanced significance analysis of microarray data based on weighted resampling: a comparative study and application to gene deletions in Mycobacterium bovis.

MOTIVATION: When analyzing microarray data, non-biological variation introduces uncertainty in the analysis and interpretation. In this paper we focus on the validation of significant differences in gene expression levels, or normalized channel intensity levels with respect to different experimental conditions and with replicated measurements. A myriad of methods have been proposed to study differences in gene expression levels and to assign significance values as a measure of confidence. In this paper we compare several methods, including SAM, regularized t-test, mixture modeling, Wilk's lambda score and variance stabilization. From this comparison we developed a weighted resampling approach and applied it to gene deletions in Mycobacterium bovis. RESULTS: We discuss the assumptions, model structure, computational complexity and applicability to microarray data. The results of our study justified the theoretical basis of the weighted resampling approach, which clearly outperforms the others.

Algorithms↗
PubMed2003

The population structure of Mycobacterium bovis in Great Britain: clonal expansion.

We have analyzed 11,500 isolates of Mycobacterium bovis (the cause of tuberculosis in cattle and other mammals) isolated in Great Britain (England, Wales and Scotland)] and characterized by spoligotype. Genetic exchange between cells is rare or absent in strains of the Mycobacterium tuberculosis complex so that, by using spoligotypes, it is possible to recognize "clones" with a recent common ancestor. The distribution of variable numbers of tandem repeats types in the most common clone in the data set is incompatible with random mutation and drift. The most plausible explanation is a series of "clonal expansions," and this interpretation is supported by the geographical distribution of different genotypes. We suggest that the clonal expansion of a genotype is caused either by the spread of a favorable mutation, together with all other genes present in the ancestral cell in which the mutation occurred, or by the invasion of a novel geographical region by a limited number of genotypes. A similar pattern is observed in M. tuberculosis (the main cause of tuberculosis in humans). The significance of clonal expansion in other bacteria that have recombination is discussed.

Bacterial Physiological Phenomena↗
PubMed2003

Inactivation of the Mycobacterium bovis homologue of the polymorphic RD1 gene Rv3879c (Mb3909c) does not affect virulence.

The RD1 locus is deleted from all strains of Mycobacterium bovis BCG but present in virulent isolates of M. bovis and Mycobacterium tuberculosis. The RD1 gene Rv3879c encodes a proline- and alanine-rich protein that shows sequence polymorphism across members of the M. tuberculosis complex. The role of this protein in virulence was investigated by deleting the Rv3879c homologue from M. bovis (Mb3909c) and testing the virulence of the mutant in the guinea pig model. The M. bovis Delta Mb3909c mutant was not attenuated in the guinea pig model, showing that this gene does not encode a virulence factor and plays no role in the attenuation caused by loss of RD1.

Animals↗
PubMed2003

Genomic analysis of Mycobacterium tuberculosis complex strains used for production of purified protein derivative.

The genomes of the tuberculin production strains Mycobacterium bovis AN5 and Mycobacterium tuberculosis DT were compared to genome-sequenced tubercle bacilli by using DNA microarrays. Neither the AN5 nor DT strain suffered extensive gene deletions during in vitro passage. This suggests that bovine tuberculin made from M. bovis AN5 is suitable to detect infection with presently prevalent M. bovis strains.

Gene Deletion↗