Biology subjects

Bannasch, D.

Publications and source records attributed to Bannasch, D..

4 recordsLinked to original sources

bioRxiv2026

The DoGA Consortium Atlas of Canine Enhancers and Promoters Across Tissues and Development

The domestic dog is a powerful genetic model for complex traits, disease and behaviours relevant to human biology, yet the canine genome still lacks a systematic transcription-defined atlas of regulatory elements. Existing resources have improved annotation but largely infer regulatory activity from chromatin features rather than directly mapping transcription initiation at promoters and enhancers. Here, we address this gap using 114 CAGE-seq libraries spanning 56 tissues and developmental stages from 9 dogs. We identify 68,446 promoters and 46,661 active enhancers, and define their tissue-enriched activity across the canine body. Regulatory programmes are organized around shared transcription factor motif infrastructures, with prominent enrichment of KLF family motifs across tissues. The cerebellum emerges as a major regulatory hub, showing the highest density of enhancer-promoter interactions among brain regions. During embryogenesis, enhancer activity shifts from early neurodevelopmental patterning programmes, including OTX2 and ZIC1/4, towards regulators of functional maturation and synaptic organization, including AQP4 and NLGN3. Comparative analyses revealed 69 enhancers with highly similar regulatory structures linked to potential orthologous genes in dog and human. Together, these data establish a tissue-resolved transcription-based atlas of the canine regulatory genome that advances functional annotation and improves interpretation of non-coding variation in comparative and disease genomics.

genomics↗

bioRxiv2025

Reproducibility of the evaluation of genetic variant pathogenicity based on the animal variant classification guidelines

Until recently, due to the absence of standardized guidelines tailored for veterinary use, the evaluation of genetic variant pathogenicity for single-gene diseases was based on a personal interpretation of the presented evidence, which has led to ambiguous interpretation. With the publication of the animal variant classification guidelines (AVCG), a more objective approach became available. Variants are evaluated based on twenty-three criteria and labeled as pathogenic, likely pathogenic, variant of uncertain significance, likely benign or benign. While the accuracy was thoroughly tested in the original publication, the reproducibility of the various steps involved was only briefly checked, which is why the current study was performed. Each variant from a set of 150 published likely causal variants for single-gene diseases from three species (dog, cat, horse) was independently and blindly assessed by three different reviewers, each applying the same AVCG. An overall agreement of 93% for decisions on the scope, i.e. whether they fit the inclusion criteria to allow evaluation with AVCG, was found. More importantly, the reproducibility was 65% for the pathogenicity classification and this increased to 83% clinically relevant agreement. While a direct comparison of the reproducibility with human literature is not possible for the scope, the reproducibility on pathogenicity classification is in line with reports using the human American College for Medical Genetics and Genomics and Association for Molecular Pathology guidelines for human variants. Overall, based on the current study, the reproducibility of the guidelines in veterinary species is within current expectations.

genetics↗

bioRxiv2020

Dog color patterns explained by modular promoters of ancient canid origin

Distinctive color patterns in dogs are an integral component of canine diversity. Color pattern differences are thought to have arisen from mutation and artificial selection during and after domestication from wolves 1,2 but important gaps remain in understanding how these patterns evolved and are genetically controlled 3,4. In other mammals, variation at the ASIP gene controls both the temporal and spatial distribution of yellow and black pigments 3,5-7. Here we identify independent regulatory modules for ventral and hair cycle ASIP expression, and we characterize their action and evolutionary origin. Structural variants define multiple alleles for each regulatory module and are combined in different ways to explain five distinctive dog color patterns. Phylogenetic analysis reveals that the haplotype combination for one of these patterns is shared with arctic white wolves and that its hair cycle-specific module likely originated from an extinct canid that diverged from grey wolves more than 2 million years before present. Natural selection for a lighter coat during the Pleistocene provided the genetic framework for widespread color variation in dogs and wolves.

genetics↗

bioRxiv2019

Quantitative translation of dog-to-human aging by conserved remodeling of epigenetic networks

Mammals progress through similar physiological stages during life, from early development to puberty, aging, and death. Yet, the extent to which this conserved physiology reflects conserved molecular events is unclear. Here, we map common epigenetic changes experienced by mammalian genomes as they age, focusing on evolutionary comparisons of humans to dogs, an emerging model of aging. Using targeted sequencing, we characterize the methylomes of 104 Labrador retrievers spanning a 16 year age range, achieving >150X coverage within mammalian syntenic blocks. Comparison with human methylomes reveals a nonlinear relationship which translates dog to human years, aligns the timing of major physiological milestones between the two species, and extends to mice. Conserved changes center on specific developmental gene networks which are sufficient to capture the effects of anti-aging interventions in multiple mammals. These results establish methylation not only as a diagnostic age readout but as a cross-species translator of physiological aging milestones.

evolutionary biology↗