Application of a west Eurasian-specific filter for quasi-median network analysis: Sharpening the blade for mtDNA error detection

Zimmermann,B.; Röck,A.; Huber,G.; Krämer,T.; Schneider,P.M.; Parson,W.; The application of quasi-median networks provides an effective tool to check the quality of mtDNA data. Filtering of highly recurrent mutations prior to network analysis is required to simplify the data set and reduce the complexity of the network. The phylogenetic background determines those mutations that need to be filtered. While the traditional EMPOPspeedy filter was based on the worldwide mtDNA phylogeny, haplogroup-specific filters can more effectively highlight potential errors in data of the respective (sub)-continental region. [Read More]

Cannabinoids lead to enhanced virulence of the smallpox vaccine (vaccinia) virus

Huemer,H.P.; Lassnig,C.; Bernhard,D.; Sturm,S.; Nowotny,N.; Kitchen,M.; Pavlic,M.; Indian hemp is used since thousands of years as herbal drug. We found that a single dose of cannabis resin was equally active as Delta9-tetrahydrocannabinol (THC) enhancing severity and duration of symptoms in vaccinia virus infected mice. Cowpox virus did not cause symptomatic disease, but some reduction of specific antibody production was observed in drug treated animals. In vitro cannabis was superior to THC alone at inhibiting mitogen stimulated proliferation of human and mouse spleen cells and peripheral blood mononuclear cells. [Read More]

CYP2D6 genotyping by liquid chromatography-electrospray ionization mass spectrometry

Beer,B.; Erb,R.; Pitterl,F.; Niederstätter,H.; Maronas,O.; Gesteira,A.; Carracedo,A.; Piatkov,I.; Oberacher,H.; Genetic polymorphisms can significantly affect the enzyme activity of the drug metabolizing enzyme Cytochrome P450 2D6 (CYP2D6; OMIM 124030). Accordingly, CYP2D6 genotyping is considered as a valid approach to predict the individual CYP2D6 metabolizing status. We introduce ion-pair reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry (ICEMS) as method for the characterization of single base variants, small deletions, and insertions in the CYP2D6 gene. [Read More]

CYP2D6 genotyping in breast cancer patients by liquid chromatography-electrospray ionization mass spectrometry

Beer,B.; Plattner,S.; Hubalek,M.; Oberguggenberger,A.; Sztankay,M.; Meraner,V.; Achleitner,R.; Oberacher,H.; The application of Cytochrome P450 2D6 (CYP2D6) genotyping to allow a personalized treatment approach for breast cancer patients undergoing endocrine therapy has been repeatedly discussed. However, the actual clinical relevance of the CYP2D6 genotype in the endocrine treatment of breast cancer still remains to be elucidated. A major prerequisite for the successful and valid evaluation of the CYP2D6 genotype with respect to its pharmacokinetic and clinical relevance is the availability of a comprehensive, accurate and cost-effective CYP2D6 genotyping strategy. [Read More]

Evaluating sequence-derived mtDNA length heteroplasmy by amplicon size analysis

Berger,C.; Hatzer-Grubwieser,P.; Hohoff,C.; Parson,W.; Length heteroplasmy (LH) in mitochondrial (mt)DNA is usually observed in homopolymeric tracts and manifest as mixture of various length variants. The generally used difference-coded annotation to report mtDNA haplotypes does not express the degree of LH variation present in a sample, even more so, it is sometimes difficult to establish which length variants are present and clearly distinguishable from background noise. It has therefore become routine practice for some researchers to call the dominant type, the “major molecule”, which represents the LH variant that is most abundant in a DNA extract. [Read More]