/ overexpression impairs neural function.

Pathogenic variants in , a gene encoding for an autophagy adaptor termed ALFY, are linked to neurodevelopmental delay and altered brain size in human probands. While the role of loss-of-function is extensively studied in neurons, little is known about the effects of upregulation in different cell types of the central nervous system (CNS). We show that overexpression of the ortholog, , in either glia or neurons impaired autophagy and locomotion.

Dysfunction of the adhesion G protein-coupled receptor latrophilin 1 (ADGRL1/LPHN1) increases the risk of obesity.

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide prevalence. Understanding the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity. G protein-coupled receptors (GPCRs) are among the main modulators of metabolism and energy balance.

Epilepsies of presumed genetic etiology show enrichment of rare variants that occur in the general population.

Previous studies suggested that severe epilepsies, e.g., developmental and epileptic encephalopathies (DEEs), are mainly caused by ultra-rare de novo genetic variants.

The role of rare genetic variants enrichment in epilepsies of presumed genetic etiology.

Previous studies suggested that severe epilepsies e.g., developmental and epileptic encephalopathies (DEE) are mainly caused by ultra-rare genetic variants.

Altered gene expression profiles impair the nervous system development in individuals with 15q13.3 microdeletion.

The 15q13.3 microdeletion has pleiotropic effects ranging from apparently healthy to severely affected individuals. The underlying basis of the variable phenotype remains elusive.

Genomic basis for skin phenotype and cold adaptation in the extinct Steller's sea cow.

Steller's sea cow, an extinct sirenian and one of the largest Quaternary mammals, was described by Georg Steller in 1741 and eradicated by humans within 27 years. Here, we complement Steller's descriptions with paleogenomic data from 12 individuals. We identified convergent evolution between Steller's sea cow and cetaceans but not extant sirenians, suggesting a role of several genes in adaptation to cold aquatic (or marine) environments.

Improving one-step scarless genome editing in by combining co-CRISPR selection with sgRNA target site masking.

The precise and rapid construction of alleles through CRISPR/Cas9-mediated genome engineering renders a powerful animal system for molecular structure-function analyses and human disease models. Application of the co-selection method offers expedited generation and enrichment of scarlessly edited alleles without the need for linked transformation markers, which specifically in the case of exon editing can impact allele usability. However, we found that knockin procedures by homology-directed repair (HDR) under co-selection resulted in low transformation efficiency.

Phenotype-tissue expression and exploration (PTEE) resource facilitates the choice of tissue for RNA-seq-based clinical genetics studies.

Background: RNA-seq emerges as a valuable method for clinical genetics. The transcriptome is "dynamic" and tissue-specific, but typically the probed tissues to analyze (TA) are different from the tissue of interest (TI) based on pathophysiology.

Results: We developed Phenotype-Tissue Expression and Exploration (PTEE), a tool to facilitate the decision about the most suitable TA for RNA-seq.

Reduced lipolysis in lipoma phenocopies lipid accumulation in obesity.

Background: Elucidation of lipid metabolism and accumulation mechanisms is of paramount importance to understanding obesity and unveiling therapeutic targets. In vitro cell models have been extensively used for these purposes, yet, they do not entirely reflect the in vivo setup. Conventional lipomas, characterized by the presence of mature adipocytes and increased adipogenesis, could overcome the drawbacks of cell cultures.