Genome Diversity and the Origin of the Arabian Horse

The Arabian horse, one of the world\u27s oldest breeds of any domesticated animal, is characterized by natural beauty, graceful movement, athletic endurance, and, as a result of its development in the arid Middle East, the ability to thrive in a hot, dry environment. Here we studied 378 Arabian horses from 12 countries using equine single nucleotide polymorphism (SNP) arrays and whole-genome re-sequencing to examine hypotheses about genomic diversity, population structure, and the relationship of the Arabian to other horse breeds. We identified a high degree of genetic variation and complex ancestry in Arabian horses from the Middle East region. Also, contrary to popular belief, we could detect no significant genomic contribution of the Arabian breed to the Thoroughbred racehorse, including Y chromosome ancestry. However, we found strong evidence for recent interbreeding of Thoroughbreds with Arabians used for flat-racing competitions. Genetic signatures suggestive of selective sweeps across the Arabian breed contain candidate genes for combating oxidative damage during exercise, and within the Straight Egyptian subgroup, for facial morphology. Overall, our data support an origin of the Arabian horse in the Middle East, no evidence for reduced global genetic diversity across the breed, and unique genetic adaptations for both physiology and conformation

Vegetation type is an important predictor of the arctic summer land surface energy budget

Despite the importance of high-latitude surface energy budgets (SEBs) for land-climate interactions in the rapidly changing Arctic, uncertainties in their prediction persist. Here, we harmonize SEB observations across a network of vegetated and glaciated sites at circumpolar scale (1994-2021). Our variance-partitioning analysis identifies vegetation type as an important predictor for SEB-components during Arctic summer (June-August), compared to other SEB-drivers including climate, latitude and permafrost characteristics. Differences among vegetation types can be of similar magnitude as between vegetation and glacier surfaces and are especially high for summer sensible and latent heat fluxes. The timing of SEB-flux summer-regimes (when daily mean values exceed 0 Wm(-2)) relative to snow-free and -onset dates varies substantially depending on vegetation type, implying vegetation controls on snow-cover and SEB-flux seasonality. Our results indicate complex shifts in surface energy fluxes with land-cover transitions and a lengthening summer season, and highlight the potential for improving future Earth system models via a refined representation of Arctic vegetation types.An international team of researchers finds high potential for improving climate projections by a more comprehensive treatment of largely ignored Arctic vegetation types, underscoring the importance of Arctic energy exchange measuring stations.Peer reviewe

Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse

Leopard complex spotting is a group of white spotting patterns in horses caused by an incompletely dominant gene (LP) where homozygotes (LP/LP) are also affected with congenital stationary night blindness. Previous studies implicated Transient Receptor Potential Cation Channel, Subfamily M, Member 1 (TRPM1) as the best candidate gene for both CSNB and LP. RNA-Seq data pinpointed a 1378 bp insertion in intron 1 of TRPM1 as the potential cause. This insertion, a long terminal repeat (LTR) of an endogenous retrovirus, was completely associated with LP, testing 511 horses (χ²=1022.00, p<<0.0005), and CSNB, testing 43 horses (χ2=43, p<<0.0005). The LTR was shown to disrupt TRPM1 transcription by premature poly-adenylation. Furthermore, while deleterious transposable element insertions should be quickly selected against the identification of this insertion in three ancient DNA samples suggests it has been maintained in the horse gene pool for at least 17,000 years. This study represents the first description of an LTR insertion being associated with both a pigmentation phenotype and an eye disorder.Rebecca R. Bellone … David L. Adelson, Sim Lin Lim … et al

Vegetation type is an important predictor of the arctic summer land surface energy budget

Despite the importance of high-latitude surface energy budgets (SEBs) for land-climate interactions in the rapidly changing Arctic, uncertainties in their prediction persist. Here, we harmonize SEB observations across a network of vegetated and glaciated sites at circumpolar scale (1994–2021). Our variance-partitioning analysis identifies vegetation type as an important predictor for SEB-components during Arctic summer (June-August), compared to other SEB-drivers including climate, latitude and permafrost characteristics. Differences among vegetation types can be of similar magnitude as between vegetation and glacier surfaces and are especially high for summer sensible and latent heat fluxes. The timing of SEB-flux summer-regimes (when daily mean values exceed 0 Wm−2) relative to snow-free and -onset dates varies substantially depending on vegetation type, implying vegetation controls on snow-cover and SEB-flux seasonality. Our results indicate complex shifts in surface energy fluxes with land-cover transitions and a lengthening summer season, and highlight the potential for improving future Earth system models via a refined representation of Arctic vegetation types

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Successful reconstruction of an ocular defect resulting from granulomatosis with polyangiitis, following treatment with rituximab

Purpose: To report a unique case of orbital inflammatory disease which was ultimately diagnosed as granulomatosis with polyangitis (GPA) and thus successfully treated. Observation: A 47 year-old man presented with a rapidly progressive necrotic soft tissue mass within the medial antero-superior aspect of the right eyelid and orbit. He also had transient retinal vasculitis in the left. Serology, histology and imaging were atypical of, but consistent with, GPA. He was thus successfully treated with intravenous rituximab followed by reconstruction of the medial eyelid. Conclusion and importance: A high index of suspicion of GPA is required in orbital inflammatory disease, especially when typical diagnostic findings are absent. Keywords: Orbital inflammatory disease, Rituximab, Eyelid reconstruction, Granulomatosis with polyangiiti

Clusters based on PCA factors.

<p>Hierarchical clustering of horses into three diagnostic categories, Healthy (red), EMS-suspect (green), and PPID-suspect (blue), using Factor 1 and Factor 2. Below clusters, four of the nine variables from the PCA across disease clusters displaying quartiles (top and bottom of red box) and median (middle line across box) using whisker-bow plots. All p-values calculated by ANOVA tests. The PPID-suspect cluster had the highest Age (p < 0.0001) and ACTH (p = 0.0003). The EMS-suspect cluster had the highest AVG BCS (p < 0.0001) and MIRG values (p = 0.0002).</p

Use of principle component analysis to quantitatively score the equine metabolic syndrome phenotype in an Arabian horse population

<div><p>Equine metabolic syndrome (EMS), like human metabolic syndrome, comprises a collection of clinical signs related to obesity, insulin dysregulation and susceptibility to secondary inflammatory disease. Although the secondary conditions resulting from EMS can be life-threatening, diagnosis is not straightforward and often complicated by the presence of other concurrent conditions like pituitary pars intermedia dysfunction (PPID). In order to better characterize EMS, we sought to describe the variation within, and correlations between, typical physical and endocrine parameters for EMS. Utilizing an unsupervised statistical approach, we evaluated a population of Arabian horses using a physical examination including body measurements, as well as blood plasma insulin, leptin, ACTH, glucose, and lipid values. We investigated the relationships among these variables using principle component analysis (PCA), hierarchical clustering, and linear regression. Owner-assigned assessments of body condition were one full score (on a nine-point scale) lower than scores assigned by researchers, indicating differing perception of healthy equine body weight. Rotated PCA defined two factor scores explaining a total of 46.3% of variation within the dataset. Hierarchical clustering using these two factors revealed three groups corresponding well to traditional diagnostic categories of “Healthy”, “PPID-suspect”, and “EMS-suspect” based on the characteristics of each group. Proxies estimating up to 93.4% of the composite “EMS-suspect” and “PPID-suspect” scores were created using a reduced set of commonly used diagnostic variables, to facilitate application of these quantitative scores to horses of the Arabian breed in the field. Use of breed-specific, comprehensive physical and endocrinological variables combined in a single quantitative score may improve detection of horses at-risk for developing EMS, particularly in those lacking severe clinical signs. Quantification of EMS without the use of predetermined reference ranges provides an advantageous approach for future studies utilizing genomic or metabolomics approaches to improve understanding of the etiology behind this troubling condition.</p></div

Summary statistics (mean ±SD) for diagnostic measures by score-defined clusters.

<p>Summary statistics (mean ±SD) for diagnostic measures by score-defined clusters.</p

Owner versus researcher reported BCS compared to the heart girth/height ratio.

<p>Owner reported body condition scores (BCS, triangles) underestimated obesity in their horse when compared to the researcher observed values (circles), potentially contributing to overfeeding. Both BCS observations correlated well with a ratio of heart girth circumference to height, suggesting the objective measurement method was an adequate proxy for adiposity/BCS.</p