Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on horse chromosome 6

<p>Abstract</p> <p>Background</p> <p>Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain horse breed where it occurs at a high frequency among Silver colored horses. The Silver coat color is associated with mutations in <it>PMEL17 </it>that resides on ECA6q23. To map the <it>MCOA </it>locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the <it>MCOA </it>locus.</p> <p>Results</p> <p>We performed linkage analysis within 17 paternal half-sib families of the Rocky Mountain horse breed. More than half of the 131 offspring had the Cyst phenotype and about one third had MCOA. Segregation data were obtained by genotyping 10 microsatellite markers most of which are positioned on ECA6q22-23, as well as the missense mutation for the Silver phenotype in <it>PMEL17</it>. Significant linkage was found between the <it>MCOA </it>locus and eight of the genetic markers, where marker <it>UPP5 </it>(Theta = 0, z = 12.3), <it>PMEL17ex11 </it>(Theta = 0, z = 19.0) and <it>UPP6 </it>(Theta = 0, z = 17.5) showed complete linkage with the <it>MCOA </it>locus. DNA sequencing of <it>PMEL17 </it>in affected and healthy control individuals did not reveal any additional mutations than the two mutations associated with the Silver coat color.</p> <p>Conclusion</p> <p>The <it>MCOA </it>locus can with high confidence be positioned within a 4.9 megabase (Mb) interval on ECA6q. The genotype data on <it>UPP5</it>, <it>PMEL17ex11 </it>and <it>UPP6 </it>strongly support the hypothesis that horses with the Cyst phenotype are heterozygous for the mutant allele and that horses with the MCOA phenotype are homozygous for the mutant allele.</p

A Software Engineering Method for the Design of Mixed Reality Systems

International audienceThe domain of Mixed Reality systems is currently making decisive advances on a daily basis. However, the knowledge and know-how of HCI scientists and interaction engineers, used in the design of such systems, is not well understood. This paper addresses this issue by proposing a software engineering method that couples a process for designing Mixed Reality interaction with a process for developing the functional core. Our development method features a Y-shaped development cycle that separates the description of functional requirements and their analysis from the study of technical requirements of the application. These sub-processes produce Business Objects and Interactional Objects, which are connected to produce a complete Mixed Reality system. The whole process is presented via a case study, with a particular emphasis on the design of the interactive solution

Isotropic three-dimensional T₂ mapping of knee cartilage: Development and validation.

1) To implement a higher-resolution isotropic 3D T &lt;sub&gt;2&lt;/sub&gt; mapping technique that uses sequential T &lt;sub&gt;2&lt;/sub&gt; -prepared segmented gradient-recalled echo (Iso3DGRE) images for knee cartilage evaluation, and 2) to validate it both in vitro and in vivo in healthy volunteers and patients with knee osteoarthritis. The Iso3DGRE sequence with an isotropic 0.6 mm spatial resolution was developed on a clinical 3T MR scanner. Numerical simulations were performed to optimize the pulse sequence parameters. A phantom study was performed to validate the T &lt;sub&gt;2&lt;/sub&gt; estimation accuracy. The repeatability of the sequence was assessed in healthy volunteers (n = 7). T &lt;sub&gt;2&lt;/sub&gt; values were compared with those from a clinical standard 2D multislice multiecho (MSME) T &lt;sub&gt;2&lt;/sub&gt; mapping sequence in knees of healthy volunteers (n = 13) and in patients with knee osteoarthritis (OA, n = 5). The numerical simulations resulted in 100 excitations per segment and an optimal radiofrequency (RF) excitation angle of 15°. The phantom study demonstrated a good correlation of the technique with the reference standard (slope 0.9 ± 0.05, intercept 0.2 ± 1.7 msec, R &lt;sup&gt;2&lt;/sup&gt; ≥ 0.99). Repeated measurements of cartilage T &lt;sub&gt;2&lt;/sub&gt; values in healthy volunteers showed a coefficient of variation of 5.6%. Both Iso3DGRE and MSME techniques found significantly higher cartilage T &lt;sub&gt;2&lt;/sub&gt; values (P &lt; 0.03) in OA patients. Iso3DGRE precision was equal to that of the MSME T &lt;sub&gt;2&lt;/sub&gt; mapping in healthy volunteers, and significantly higher in OA (P = 0.01). This study successfully demonstrated that high-resolution isotropic 3D T &lt;sub&gt;2&lt;/sub&gt; mapping for knee cartilage characterization is feasible, accurate, repeatable, and precise. The technique allows for multiplanar reformatting and thus T &lt;sub&gt;2&lt;/sub&gt; quantification in any plane of interest. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:362-371

Running and Physical Activity in an Air-Polluted Environment: The Biomechanical and Musculoskeletal Protocol for a Prospective Cohort Study 4HAIE (Healthy Aging in Industrial Environment—Program 4)

Far too little attention has been paid to health effects of air pollution and physical (in)activity on musculoskeletal health. The purpose of the Healthy aging in industrial environment study (4HAIE) is to investigate the potential impact of physical activity in highly polluted air on musculoskeletal health. A total of 1500 active runners and inactive controls aged 18–65 will be recruited. The sample will be recruited using quota sampling based on location (the most air-polluted region in EU and a control region), age, sex, and activity status. Participants will complete online questionnaires and undergo a two-day baseline laboratory assessment, including biomechanical, physiological, psychological testing, and magnetic resonance imaging. Throughout one-year, physical activity data will be collected through Fitbit monitors, along with data regarding the incidence of injuries, air pollution, psychological factors, and behavior collected through a custom developed mobile application. Herein, we introduce a biomechanical and musculoskeletal protocol to investigate musculoskeletal and neuro-mechanical health in this 4HAIE cohort, including a design for controlling for physiological and psychological injury factors. In the current ongoing project, we hypothesize that there will be interactions of environmental, biomechanical, physiological, and psychosocial variables and that these interactions will cause musculoskeletal diseases/protection

BIOMECHANICS IN THE 4HAIE STUDY: AIR POLLUTION AND MUSCULOSKELETAL HEALTH - AN UPDATE

The overall purpose of the 4HAIE study was to assess the influence of the interaction between air pollution and biomechanical, physiological and psychosocial factors on the incidence of injuries, health and well-being. A total of 1,500 active runners and inactive controls aged 18-65 will be recruited. Herein, we describe the biomechanical study design with data examples to investigate musculoskeletal and neuro-mechanics health in different air quality regions

Copy Number Variation in the Horse Genome

We constructed a 400K WG tiling oligoarray for the horse and applied it for the discovery of copy number variations (CNVs) in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Probes on the array represented 18,763 autosomal and X-linked genes, and intergenic, sub-telomeric and chrY sequences. We identified 258 CNV regions (CNVRs) across all autosomes, chrX and chrUn, but not in chrY. CNVs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred reference. The Przewalski horse was similar to native ponies and draft breeds. The majority of CNVRs involved genes, while 20% were located in intergenic regions. Similar to previous studies in horses and other mammals, molecular functions of CNV-associated genes were predominantly in sensory perception, immunity and reproduction. The findings were integrated with previous studies to generate a composite genome-wide dataset of 1476 CNVRs. Of these, 301 CNVRs were shared between studies, while 1174 were novel and require further validation. Integrated data revealed that to date, 41 out of over 400 breeds of the domestic horse have been analyzed for CNVs, of which 11 new breeds were added in this study. Finally, the composite CNV dataset was applied in a pilot study for the discovery of CNVs in 6 horses with XY disorders of sexual development. A homozygous deletion involving AKR1C gene cluster in chr29 in two affected horses was considered possibly causative because of the known role of AKR1C genes in testicular androgen synthesis and sexual development. While the findings improve and integrate the knowledge of CNVs in horses, they also show that for effective discovery of variants of biomedical importance, more breeds and individuals need to be analyzed using comparable methodological approaches.Sharmila Ghosh, Zhipeng Qu, Pranab J. Das, Erica Fang, Rytis Juras, E. Gus Cothran, Sue McDonell, Daniel G. Kenney, Teri L. Lear, David L. Adelson, Bhanu P. Chowdhary, Terje Raudsep

Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases

The syndrome Multiple Congenital Ocular Anomalies (MCOA) is the collective name ascribed to heritable congenital eye defects in horses. Individuals homozygous for the disease allele (MCOA phenotype) have a wide range of eye anomalies, while heterozygous horses (Cyst phenotype) predominantly have cysts that originate from the temporal ciliary body, iris, and/or peripheral retina. MCOA syndrome is highly prevalent in the Rocky Mountain Horse but the disease is not limited to this breed. Affected horses most often have a Silver coat color; however, a pleiotropic link between these phenotypes is yet to be proven. Locating and possibly isolating these traits would provide invaluable knowledge to scientists and breeders. This would favor maintenance of a desirable coat color while addressing the health concerns of the affected breeds, and would also provide insight into the genetic basis of the disease. Identical-by-descent mapping was used to narrow the previous 4.6-Mb region to a 264-kb interval for the MCOA locus. One haplotype common to four breeds showed complete association to the disease (Cyst phenotype, n = 246; MCOA phenotype, n = 83). Candidate genes from the interval, SMARCC2 and IKZF4, were screened for polymorphisms and genotyped, and segregation analysis allowed the MCOA syndrome region to be shortened to 208 kb. This interval also harbors PMEL17, the gene causative for Silver coat color. However, by shortening the MCOA locus by a factor of 20, 176 other genes have been unlinked from the disease and only 15 genes remain

Cost management : a strategic emphasis

xxvii, 948 p. ; 26 cm

Cost management : a strategic emphasis

xxxi, 891 p. ; 27 cm