Musculoskeletal disorders are one of the leading causes of morality in neonatal Thoroughbred foals. Contracted Foal Syndrome (CFS) has accounted for up to 48% of such disorders in foals submitted for necropsy according to the Kentucky Livestock Diagnostic Center and is reportedly a concern to clinicians and breeders. CFS is primarily characterized by limb contractures and other malformations of the appendicular and/or axial skeleton. Foals are often euthanized in severe cases and successful rehabilitation in moderate cases does not entirely negate secondary complications. Because of the economic implications associated with treatment costs, owners may opt to euthanize foals even though they potentially could have led productive lives. A familial predisposition was observed in some cases. In addition, veterinarians reported increased incidence of contracted foals in one particular sire line. This, coupled with model genetic disorders in other species, prompted us to conduct the first molecular genetics study on congenital flexion and CFS. The inconsistent nature of clinical documentation and variable phenotypes pose a challenge to researchers investigating such complex conditions. We therefore conducted a detailed analysis of the phenotypes and used the data to propose a preliminary classification system that could be used by clinicians and researchers. The implementation of such a classification system will reduce ambiguity of clinical documentation and provide the basis for future study designs. Our hypothesis states, that in some cases, flexion contractures and CFS are major gene disorders with the likelihood of genetic heterogeneity. Our first approach was to sequence the candidate gene, tropomyosin beta 2. This gene encodes a component of the skeletal muscle contractile apparatus and has been implicated in congenital distal limb contractures in humans. Next, new utilized the newly available Equine SNP50 Beadchip for a case/control population based genome-wide association mapping approach followed by a family validation study and family based genome-wide association study. These approaches resulted in the identification of associations between various subtypes of contracted foals and at least 3 disease susceptibility loci. In summary, this study provides insight into the genetics underlying flexion contractures and CFS in the neonatal foal and has proved the first evidence for a genetic cause. Furthermore, it provides a solid foundation for future research targeting candidate genes for resequencing. Advisors/Committee Members: Chowdhary, Bhanu P (advisor), Gill, Clare A (committee member), Raudsepp, Terje (committee member), Seabury, Christopher (committee member), Moyer, William (committee member).

This dissertation investigated locational risks to ecosystem health associated with proximity to industrial complexes. The study was performed at the behest of ranchers and citizens living and working down-prevailing wind from the Formosa Plastics, Inc. and ALCOA facilities located in Calhoun County, Texas. Concerns expressed were for potential genotoxicity resulting from exposure to complex chemical mixtures released by the facilities. Exposure assessment of the marine environment was performed with sediments and oysters from Lavaca Bay being analyzed. Numerous chemicals were found to be present at concentrations considered likely to result in adverse responses in exposed populations. Bayesian geostatistical analysis was performed to determine if the concentrations were affected by a spatial process. Mercury and polycyclic aromatic hydrocarbons were the most notable of the chemicals found to be present at elevated concentrations and affected by a spatial process. Evaluation of maps generated from spatial modeling revealed that proximity to ALCOA resulted in elevated risks for exposure to harmful concentrations of pollutants. Genotoxicity was measured in two sentinel species. Oysters (Crassostrea virginica) were utilized for evaluation of the marine environment and cattle (Bos taurus and Bos taurus crossbred cattle) were chosen for evaluation of the terrestrial environment. Chromosomal aberration analysis was performed on oyster hematocytes. Analysis of the results failed to demonstrate the presence of an important generalized spatial process but some specific locations close to the ALCOA plant had elevations in this measure of genotoxicity. Stress as measured by the lysosomal destabilization assay was also performed on oyster hematocytes. These results were found to be affected by a significant spatial process with the highest degree of destabilization occurring in close proximity to ALCOA. Genotoxicity in cattle was evaluated with the single cell gel electrophoresis assay and chromosomal aberration analysis. Bayesian geostatistical analyis revealed the presence of important spatial processes. DNA-protein cross-linkage was the most notable with a strong indication of increased damage down-prevailing wind from the industrial complexes. Results indicated that proximity to industrial facilities increased the risk for harmful exposures, genotoxicity, and lysosomal destabilization. Advisors/Committee Members: Adams, L. Garry (advisor), Thompson, James A. (advisor), Field, Robert (committee member), Moyer, William (committee member), Phillips, Timothy (committee member), Scott, H. Morgan (committee member).