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8 results on '"Drukewitz, Stephan H"'

2. Case report: Complete paternal isodisomy on chromosome 18 induces methylation changes in PARD6G-AS1 promotor in a case with arthrogryposis.

Author

Moch, Johanna, Radtke, Maximilian, Gburek-Augustat, Janina, Karnstedt, Maike, Schönnagel, Senta, Drukewitz, Stephan H., Pilgram, Laura, Hentschel, Julia, and Schumann, Isabell

Subjects
ARTHROGRYPOSIS, GENETIC variation, METHYLATION, MUSCLE weakness, PANEL analysis, CHROMOSOMES, MOTOR learning
Abstract

Uniparental disomy (UPD) is the inheritance of both alleles of a chromosome from only one parent. So far, the detection of UPDs in sequencing data is not well established and a known gap in next-generation sequencing (NGS) diagnostics. By developing a new tool for UPD detection, we re-evaluated an eight-year-old individual presenting with scoliosis, muscle weakness and global developmental delay. Previous panel analysis identified a homozygous likely pathogenic loss-of- function variant in the PIEZO2-gene associated with arthrogryposis (OMIM # 617146). Interestingly, during a re-evaluation process, we identified a region of homozygosity (ROH) covering over 95% of chromosome 18. Segregation and microsatellite analysis within the family revealed that only the father is a heterozygous carrier of the variant in PIEZO2 and confirmed paternal uniparental isodisomy (iUPD) on chromosome 18 in the individual. Further methylation analysis indicated demethylation of the promotor region of PARD6G-AS1, which is described to be maternally imprinted and could possibly influence the individuals’ phenotype. Our report describes the first complete iUPD on chromosome 18 and highlights that UPDs can be a cause for homozygous pathogenic variants, which reduces the risk of reoccurrence in case of a new pregnancy in comparison to an autosomal recessive inheritance trait significantly. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Toxins from scratch? Diverse, multimodal gene origins in the predatory robber fly Dasypogon diadema indicate a dynamic venom evolution in dipteran insects

Author

Drukewitz, Stephan H., Bokelmann, Lukas, Undheim, Eivind Andreas Baste, von Reumont, Bjorn M, and Publica

Subjects
fungi, complex mixtures
Abstract

Venoms and the toxins they contain represent molecular adaptations that have evolved on numerous occasions throughout the animal kingdom. However, the processes that shape venom protein evolution are poorly understood because of the scarcity of whole-genome data available for comparative analyses of venomous species. We performed a broad comparative toxicogenomic analysis to gain insight into the genomic mechanisms of venom evolution in robber flies (Asilidae). We first sequenced a high-quality draft genome of the hymenopteran hunting robber fly Dasypogon diadema, analysed its venom by a combined proteotranscriptomic approach, and compared our results with recently described robber fly venoms to assess the general composition and major components of asilid venom. We then applied a comparative genomics approach, based on 1 additional asilid genome, 10 high-quality dipteran genomes, and 2 lepidopteran outgroup genomes, to reveal the evolutionary mechanisms and origins of identified venom proteins in robber flies. While homologues were identified for 15 of 30 predominant venom protein in the non-asilid genomes, the remaining 15 highly expressed venom proteins appear to be unique to robber flies. Our results reveal that the venom of D. diadema likely evolves in a multimodal fashion comprising (i) neofunctionalization after gene duplication, (ii) expression-dependent co-option of proteins, and (iii) asilid lineage-specific orphan genes with enigmatic origin. The role of such orphan genes is currently being disputed in evolutionary genomics but has not been discussed in the context of toxin evolution. Our results display an unexpected dynamic venom evolution in asilid insects, which contrasts the findings of the only other insect toxicogenomic evolutionary analysis, in parasitoid wasps (Hymenoptera), where toxin evolution is dominated by single gene co-option. These findings underpin the significance of further genomic studies to cover more neglected lineages of venomous taxa and to understand the importance of orphan genes as possible drivers for venom evolution.

Published
2019

5. Breaking the ladder: Evolution of the ventral nerve cord in Annelida

Author

Helm, Conrad, primary, Beckers, Patrick, additional, Bartolomaeus, Thomas, additional, Drukewitz, Stephan H., additional, Kourtesis, Ioannis, additional, Weigert, Anne, additional, Purschke, Günter, additional, Worsaae, Katrine, additional, Struck, Torsten H., additional, and Bleidorn, Christoph, additional

Published
2018
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6. Comparative analyses of glycerotoxin expression unveil a novel structural organization of the bloodworm venom system

Author

German Research Foundation, European Commission, University College London, Cancer Research UK, Leipzig University, Richter, Sandy, Helm, Conrad, Meunier, Frederic A., Hering, Lars, Campbell, Lahcen I., Drukewitz, Stephan H., Undheim, Eivind A. B., Jenner, Ronald A., Schiavo, Giampietro, Bleidorn, Christoph, German Research Foundation, European Commission, University College London, Cancer Research UK, Leipzig University, Richter, Sandy, Helm, Conrad, Meunier, Frederic A., Hering, Lars, Campbell, Lahcen I., Drukewitz, Stephan H., Undheim, Eivind A. B., Jenner, Ronald A., Schiavo, Giampietro, and Bleidorn, Christoph

Abstract

[Background]: We present the first molecular characterization of glycerotoxin (GLTx), a potent neurotoxin found in the venom of the bloodworm Glycera tridactyla (Glyceridae, Annelida). Within the animal kingdom, GLTx shows a unique mode of action as it can specifically up-regulate the activity of Cav2.2 channels (N-type) in a reversible manner. The lack of sequence information has so far hampered a detailed understanding of its mode of action., [Results]: Our analyses reveal three ~3.8 kb GLTx full-length transcripts, show that GLTx represents a multigene family, and suggest it functions as a dimer. An integrative approach using transcriptomics, quantitative real-time PCR, in situ hybridization, and immunocytochemistry shows that GLTx is highly expressed exclusively in four pharyngeal lobes, a previously unrecognized part of the venom apparatus., [Conclusions]: Our results overturn a century old textbook view on the glycerid venom system, suggesting that it is anatomically and functionally much more complex than previously thought. The herein presented GLTx sequence information constitutes an important step towards the establishment of GLTx as a versatile tool to understand the mechanism of synaptic function, as well as the mode of action of this novel neurotoxin.

Published
2017

7. Comparative analyses of glycerotoxin expression unveil a novel structural organization of the bloodworm venom system

Author

Richter, Sandy, Helm, Conrad, Meunier, Frederic A, Hering, Lars, Campbell, Lahcen I, Drukewitz, Stephan H, Undheim, Eivind AB, Jenner, Ronald, Schiavo, Giampietro, Bleidorn, Christoph, Richter, Sandy, Helm, Conrad, Meunier, Frederic A, Hering, Lars, Campbell, Lahcen I, Drukewitz, Stephan H, Undheim, Eivind AB, Jenner, Ronald, Schiavo, Giampietro, and Bleidorn, Christoph

Abstract

Background: We present the first molecular characterization of glycerotoxin (GLTx), a potent neurotoxin found in the venom of the bloodworm Glycera tridactyla (Glyceridae, Annelida). Within the animal kingdom, GLTx shows a unique mode of action as it can specifically up-regulate the activity of Cav2.2 channels (N-type) in a reversible manner. The lack of sequence information has so far hampered a detailed understanding of its mode of action. Results: Our analyses reveal three ~3.8 kb GLTx full-length transcripts, show that GLTx represents a multigene family, and suggest it functions as a dimer. An integrative approach using transcriptomics, quantitative real-time PCR, in situ hybridization, and immunocytochemistry shows that GLTx is highly expressed exclusively in four pharyngeal lobes, a previously unrecognized part of the venom apparatus. Conclusions: Our results overturn a century old textbook view on the glycerid venom system, suggesting that it is anatomically and functionally much more complex than previously thought. The herein presented GLTx sequence information constitutes an important step towards the establishment of GLTx as a versatile tool to understand the mechanism of synaptic function, as well as the mode of action of this novel neurotoxin.

Published
2017

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