A5058810328- Neurological diseases and metabolism
- Genetic and phenotypic traits in livestock
- Cancer-related molecular mechanisms research
- Hereditary Neurological Disorders
- Genetic Mapping and Diversity in Plants and Animals
- Animal Genetics and Reproduction
- Botulinum Toxin and Related Neurological Disorders
- Wnt/β-catenin signaling in development and cancer
- Milk Quality and Mastitis in Dairy Cows
- RNA Research and Splicing
- Veterinary Equine Medical Research
- Genomics and Phylogenetic Studies
- melanin and skin pigmentation
- Animal Virus Infections Studies
- Immune Response and Inflammation
- Connexins and lens biology
- Epigenetics and DNA Methylation
- Genetic and Kidney Cyst Diseases
- Genetics and Neurodevelopmental Disorders
- Congenital limb and hand anomalies
- Lysosomal Storage Disorders Research
- Amino Acid Enzymes and Metabolism
- Retinal Development and Disorders
- Identification and Quantification in Food
- Skin and Cellular Biology Research
Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie
2024
Johannes Gutenberg University Mainz
2019-2024
Research Institute for Farm Animal Biology (FBN)
2019-2023
University of Pennsylvania
2015-2020
University of Bern
2009-2020
Penn Center for AIDS Research
2018-2019
Kiel University
2018
Charité - Universitätsmedizin Berlin
2007-2014
Institute for Prevention and Occupational Medicine
2008
Abstract Innate immunity relies on pattern recognition receptors to detect the presence of infectious pathogens. In case Gram-positive bacteria, binding bacterial lipopeptides TLR2 is currently regarded as an important mechanism. present study, we used synthetic lipopeptide Pam3CysSK4, a selective agonist, induce meningeal inflammation in rodents. 6-h rat model, intrathecal application Pam3CysSK4 caused influx leukocytes into cerebrospinal fluid (CSF) and induced marked increase regional...
Osteogenesis imperfecta (OI) is a hereditary disease occurring in humans and dogs. It characterized by extremely fragile bones teeth. Most human some canine OI cases are caused mutations the COL1A1 COL1A2 genes encoding subunits of collagen I. Recently, CRTAP LEPRE1 were found to cause rare forms OI. Many exist where causative mutation has not yet been found. We investigated Dachshunds with an autosomal recessive form Genotyping only five affected dogs on 50 k SNP chip allowed us localize...
Inherited neurodegenerative disorders are debilitating diseases that occur across different species. We have performed clinical, pathological and genetic studies to characterize a novel canine disease present in the Lagotto Romagnolo dog breed. Affected dogs suffer from progressive cerebellar ataxia, sometimes accompanied by episodic nystagmus behavioral changes. Histological examination revealed unique changes, including profound neuronal cytoplasmic vacuolization nervous system, as well...
Abstract Mitochondrial topoisomerase IB (TOP1MT) is a nuclear-encoded topoisomerase, exclusively localized to mitochondria, which resolves topological stress generated during mtDNA replication and transcription. Here, we report that TOP1MT overexpressed in cancer tissues demonstrate deficiency attenuates tumor growth human mouse models of colon liver cancer. Due their mitochondrial dysfunction, TOP1MT-KO cells become addicted glycolysis, limits synthetic building blocks energy supply...
Microphthalmia in sheep is an autosomal recessive inherited congenital anomaly found within the Texel breed. It characterized by extremely small or absent eyes and affected lambs are absolutely blind. For first time, we use a genome-wide ovine SNP array for positional cloning of Mendelian trait sheep. Genotyping 23 cases controls using Illumina's OvineSNP50 BeadChip allowed us to localize causative mutation microphthalmia 2.4 Mb interval on chromosome 22 association homozygosity mapping. The...
Hereditary footpad hyperkeratosis (HFH) represents a palmoplantar hyperkeratosis, which is inherited as monogenic autosomal recessive trait in several dog breeds, such e.g. Kromfohrländer and Irish Terriers. We performed genome-wide association studies (GWAS) both breeds. In we obtained single strong signal on chromosome 5 (praw = 1.0×10−13) using 13 HFH cases 29 controls. The replicated an independent cohort of Terriers with 10 21 controls 6.9×10−10). analysis shared haplotypes among the...
Summary The recent development of a goat SNP genotyping microarray enables genome‐wide association studies in this important livestock species. We investigated the genetic basis black and brown coat colour Valais Blacknecked Coppernecked goats. A analysis using 50 BeadChip genotypes 22 cases 23 controls allowed us to map locus for chromosome 8. TYRP 1 gene is located within associated chromosomal region, variants cause similar phenotypes different thus considered as strong positional...
The improvement of meat quality and production traits has high priority in the pork industry. Many these show a low to moderate heritability are difficult expensive measure. Their by targeted breeding programs is challenging requires knowledge genetic molecular background. For this study we genotyped 192 artificial insemination boars commercial line derived from Swiss Large White breed using PorcineSNP60 BeadChip with 62,163 evenly spaced SNPs across pig genome. We obtained 26 estimated...
An inherited polyneuropathy (PN) observed in Leonberger dogs has clinical similarities to a genetically heterogeneous group of peripheral neuropathies termed Charcot-Marie-Tooth (CMT) disease humans. The disorder is severe, juvenile-onset, chronic, progressive, and mixed PN, characterized by exercise intolerance, gait abnormalities muscle atrophy the pelvic limbs, as well inspiratory stridor dyspnea. We mapped PN locus Leonbergers 250 kb region on canine chromosome 16 (Praw = 1.16×10−10,...
The polyneuropathy of juvenile Greyhound show dogs shows clinical similarities to the genetically heterogeneous Charcot-Marie-Tooth (CMT) disease in humans. pedigrees containing affected suggest monogenic autosomal recessive inheritance and all trace back a single male. Here, we studied neuropathology this identified candidate causative mutation. Peripheral nerve biopsies from were examined using semi-thin histology, fibre teasing electron microscopy. A severe chronic progressive mixed was...
The presence of congenital appendages (wattles) on the throat goats is supposed to be under genetic control with a dominant mode inheritance. Wattles contain cartilaginous core covered normal skin resembling early stages extremities. To map caprine wattles (W) locus, we collected samples 174 and 167 without from nine different Swiss goat breeds. were genotyped 53k SNP chip for subsequent genome-wide association study. We obtained single strong signal chromosome 10 in region containing...
Many inherited polyneuropathies (PN) observed in dogs have clinical similarities to the genetically heterogeneous group of Charcot-Marie-Tooth (CMT) peripheral neuropathies humans. The canine disorders collectively show a variable expression progressive signs and ages onset, different breed prevalences. Previously Leonberger breed, variant highly associated with juvenile-onset PN was identified orthologue CMT-associated gene. As this deletion ARHGEF10 (termed LPN1) does not explain all...
<b>Introduction:</b> Early assessment of a therapeutic response is central goal in antidepressant treatment. The present study examined the potential for drug monitoring and symptom rating to predict venlafaxine treatment efficacy (measured by overall patient remission). <b>Methods:</b> 88 patients were uptitrated homogenously 225 mg/day venlafaxine. Serum concentrations (VEN) its active metabolite O-desmethylvenlafaxine (ODV) measured at week 2. Continuous psychopathometric ratings up 6...
Abstract Congenital stationary night blindness (CSNB), in the complete form, is caused by dysfunctions ON-bipolar cells (ON-BCs) which are secondary neurons of retina. We describe first disease causative variant associated with CSNB dog. A genome-wide association study using 12 cases and 11 controls from a research colony determined 4.6 Mb locus on canine chromosome 32. Subsequent whole-genome sequencing identified 1 bp deletion LRIT3 segregating CSNB. The mutant gives rise to truncated...
Mastitis is one of the major risks for public health and animal welfare in dairy industry. Two most important pathogens to cause mastitis cattle are Staphylococcus aureus (S. aureus) Escherichia coli (E. coli). While S. generally induces a chronic subclinical mastitis, E. an etiological pathogen resulting acute clinical mastitis. The liver plays central role both, metabolic inflammatory physiology cow, which particularly challenged early lactation due high immunological demands. In current...
Alterations of blood flow contribute to major clinical complications in invasive infections such as sepsis and bacterial meningitis. As a unique feature streptococci – particular, Streptococcus pneumoniae, the most frequent pathogen meningitis release hydrogen peroxide (H 2 O ) because absence functional catalase. In 6 h rat model experimental meningitis, we studied impact H production on regional cerebral (rCBF) intracranial pressure (ICP). Compared wild-type D39 pneumococci, increase rCBF...
Abstract Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP cohort dog chromosome 18. Subsequent whole genome re-sequencing case enabled identification single private homozygous non-synonymous missense variant located highly conserved metallo-beta-lactamase domain N-acyl phosphatidylethanolamine phospholipase D ( NAPEPLD...
Abstract Aberrant photoreceptor function or morphogenesis leads to blinding retinal degenerative diseases, the majority of which have a genetic aetiology. A variant in PRCD previously identified Portuguese Water Dogs (PWDs) underlies prcd (progressive rod-cone degeneration), an autosomal recessive progressive atrophy (PRA) with late onset at 3–6 years age older. Herein, we new form early-onset PRA (EOPRA) same breed. Pedigree analysis suggested inheritance. Four PWD full-siblings affected...
Rod and cone photoreceptors are specialized retinal neurons that have a fundamental role in visual perception, capturing light transducing it into neuronal signal. Aberrant functioning of rod and/or can ultimately lead to progressive degeneration eventually blindness. In man, many rod-cone degenerative diseases classified as forms retinitis pigmentosa (RP). Dogs also comparable disease grouping termed atrophy (PRA). These generally due single gene defects follow Mendelian inheritance.We...
Bovine mammary function at molecular level is often studied using tissue or primary bovine epithelial cells (pbMECs). However, bulk and are heterogeneous with respect to cell populations, adding further transcriptional variation in addition genetic background. Thus, understanding of the gene expression profiles populations their effect on limited. To investigate mononuclear composition milk, we analyzed a single-cell suspension from milk sample. Additionally, harvested cultured pbMECs...
Understanding the genomic control of tissue-specific gene expression and regulation can help to inform application technologies in farm animal breeding programs. The fine mapping promoters [transcription start sites (TSS)] enhancers (divergent amplifying segments genome local TSS) different populations cattle across a wide diversity tissues provides information locate understand drivers breed- characteristics. To this aim, we used Cap Analysis Gene Expression (CAGE) sequencing, 24 from 3...
The sugar molecule N-glycolylneuraminic acid (Neu5Gc) is one of the most common sialic acids discovered in mammals. Cytidine monophospho-N-acetylneuraminic hydroxylase (CMAH) catalyses conversion N-acetylneuraminic (Neu5Ac) to Neu5Gc, and it encoded by CMAH gene. On hand, food metabolic incorporation Neu5Gc has been linked specific human diseases. other shown be highly preferred some pathogens certain bovine We used various computational techniques perform an silico functional analysis five...
Purpose: To define genetic variants associated with variable severity of X-linked progressive retinal atrophy 1 (XLPRA1) caused by a five-nucleotide deletion in canine RPGR exon ORF15. Methods: A genome-wide association study (GWAS) was performed XLPRA1 phenotype informative pedigree. Whole genome sequencing (WGS) used for mutational analysis genes within the candidate genomic region. Retinas normal and mutant dogs were gene expression, structure, RNA duplex analyses. Results: GWAS followed...