In humans, the clinical and molecular characterization of sporadic syndromes is often hindered by the small number of patients and the difficulty in developing animal models for severe dominant conditions. Here we show that the availability of large data sets of whole-genome sequences, high-density SNP chip genotypes and extensive recording of phenotype offers an unprecedented opportunity to quickly dissect the genetic architecture of severe dominant conditions in livestock. We report on the identification of seven dominant de novo mutations in CHD7, COL1A1, COL2A1, COPA, and MITF and exploit the structure of cattle populations to describe their clinical consequences and map modifier loci. Moreover, we demonstrate that the emergence of recessive genetic defects can be monitored by detecting de novo deleterious mutations in the genome of bulls used for artificial insemination. These results demonstrate the attractiveness of cattle as a model species in the post genomic era, particularly to confirm the genetic aetiology of isolated clinical case reports in humans.

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High and Low Activity strains of mice (displaying low and high anxiety-like behavior, respectively) with 7.8-20 fold differences in open-field activity were selected and subsequently inbred to use as a genetic model for studying anxiety-like behavior in mice (DeFries et al., 1978, Behavior Genetics, 8:3-13). These strains exhibited differences in other anxiety-related behaviors as assessed using the light-dark box, elevated plus-maze, mirror chamber, and elevated square-maze tests (Henderson et al., 2004, Behavior Genetics, 34: 267-293). The purpose of these experiments was three-fold. First, we repeated a 6-day behavioral battery using updated equipment

The 16S-23S rRNA Internal Transcribed Spacer (ITS) is a commonly employed taxonomic marker in cyanobacterial systematics. Due to numerous challenges in articulating phylogenetic relationships within this ubiquitous, ancient lineage, a polyphasic approach including 16S rRNA sequence data, ecology, morphology, and ITS secondary structure analysis has become the standard. In particular, the ITS motifs are being utilized in the erection of novel and cryptic taxa. However, this is challenging as researchers must manually mine and parse sequence data to visually find and identify ITS structures. This painstaking process deters researchers from using ITS motifs, may lead to inconsistencies, and is a rather dry, tedious enterprise. Thus, we present a simple, user-friendly web-based application for help in finding and preparing the most common cyanobacterial motifs (e.g., the Box-B, D1-D1´, tRNAs, etc.). After extensive testing, we note that the most common motifs are recovered at ca. 97%. These motifs can then be easily exported into Mfold or other similar folding packages. We hope that this will both provide a valuable tool for researchers but will also facilitate new discoveries and allow for greater consistency in publishing ITS comparisons. The tool can be accessed at www.phylo.dev.

High and Low Activity strains of mice were bidirectionally selected for differences in open‐field activity (DeFries et al., 1978, Behavior Genetics, 8: 3–13) and subsequently inbred to use as a genetic model for studying anxiety‐like behaviors (Booher et al., 2021, Genes, Brain and Behavior, 20: e12730). Hippocampal RNA‐sequencing of the High and Low Activity mice identified 3901 differentially expressed protein‐coding genes, with both sex‐dependent and sex‐independent effects. Functional enrichment analysis (PANTHER) highlighted 15 gene ontology terms, which allowed us to create a narrow list of 264 top candidate genes. Of the top candidate genes, 46 encoded four Complexes (I, II, IV and V) and two electron carriers (cytochrome c and ubiquinone) of the mitochondrial oxidative phosphorylation process. The most striking results were in the female high anxiety, Low Activity mice, where 39/46 genes relating to oxidative phosphorylation were upregulated. In addition, comparison of our top candidate genes with two previously curated High and Low Activity gene lists highlight 24 overlapping genes, where Ndufa13, which encodes the supernumerary subunit A13 of complex I, was the only gene to be included in all three lists. Mitochondrial dysfunction has recently been implicated as both a cause and effect of anxiety‐related disorders and thus should be further explored as a possible novel pharmaceutical treatment for anxiety disorders.

Cyanobacteria are diverse prokaryotic, photosynthetic organisms present in nearly every known ecosystem. Recent investigations around the world have recovered vast amounts of novel biodiversity in seldom sampled habitats. One phylogenetically significant character, the secondary folding structures of the 16S–23S ITS rDNA region, has allowed an unprecedented capacity to erect new species. However, two questions arise: Is this feature as informative as is proposed, and how do we best employ these features? Submerged sinkholes with oxygen‐poor, sulfur‐rich ground water in Lake Huron (USA) contain microbial mats dominated by both oxygenic and anoxygenic cyanobacteria. We sought to document some of this unique cyanobacterial diversity. Using culture‐based investigations, we recovered 45 strains, of which 23 were analyzed employing 16S–23S rDNA sequences, ITS folding patterns, ecology, and morphology. With scant morphological discontinuities and nebulous 16S rDNA gene sequence divergence, ITS folding patterns were effective at articulating cryptic biodiversity. However, we would have missed these features had we not folded all the available motifs from the strains, including those with highly similar 16S rDNA gene sequences. If we had relied solely on morphological or 16S rDNA gene data, then we might well have missed the diversity of Anagnostidinema. Thus, in order to avoid conformation basis, which is potentially common when employing ITS structures, we advocate clustering strains based on ITS rDNA region patterns independently and comparing them back to 16S rDNA gene phylogenies. Using a total evidence approach, we erected a new taxon according to the International Code of Nomenclature for Algae, Fungi, and Plants: Anagnostidinema visiae.

Anxiety disorders are common and can be debilitating, with effective treatments remaining hampered by an incomplete understanding of the underlying genetic etiology. Improvements have been made in understanding the genetic influences on mouse behavioral models of anxiety, yet it is unclear the extent to which genes identified in these experimental systems contribute to genetic variation in human anxiety phenotypes. Leveraging new and existing large-scale human genome-wide association studies, we tested whether sets of genes previously identified in mouse anxiety-like behavior studies contribute to a range of human anxiety disorders. When tested as individual genes, thirteen mouse-identified genes were associated with human anxiety phenotypes, suggesting an overlap of individual genes contributing to both mouse models of anxiety-like behaviors and human anxiety traits. When genes were tested as sets, we did identify fourteen significant associations between mouse gene sets and human anxiety, but the majority of gene sets showed no significant association with human anxiety phenotypes. These few significant associations indicate a need to identify and develop more translatable mouse models by identifying sets of genes that 'match' between model systems and specific human phenotypes of interest. We suggest that continuing to develop improved behavioral paradigms and finer-scale experimental data, for instance from individual neuronal subtypes or cell-type-specific expression data, is likely to improve our understanding of the genetic etiology and underlying functional changes in anxiety disorders.

Anxiety disorders are common and can be debilitating, with effective treatments remaining hampered by an incomplete understanding of the underlying genetic etiology. Improvements have been made in understanding the genetic influences on mouse behavioral models of anxiety, yet it is unclear the extent to which genes identified in these experimental systems contribute to genetic variation in human anxiety phenotypes. Leveraging new and existing large‐scale human genome‐wide association studies, we tested whether sets of genes previously identified in mouse anxiety‐like behavior studies contribute to a range of human anxiety disorders. When tested as individual genes, 13 mouse‐identified genes were associated with human anxiety phenotypes, suggesting an overlap of individual genes contributing to both mouse models of anxiety‐like behaviors and human anxiety traits. When genes were tested as sets, we did identify 14 significant associations between mouse gene sets and human anxiety, but the majority of gene sets showed no significant association with human anxiety phenotypes. These few significant associations indicate a need to identify and develop more translatable mouse models by identifying sets of genes that “match” between model systems and specific human phenotypes of interest. We suggest that continuing to develop improved behavioral paradigms and finer‐scale experimental data, for instance from individual neuronal subtypes or cell‐type‐specific expression data, is likely to improve our understanding of the genetic etiology and underlying functional changes in anxiety disorders.