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Metabogenomics reveals four candidate regions involved in the pathophysiology of Equine Metabolic Syndrome.

ABSTRACT: An analogous condition to human metabolic syndrome, Equine Metabolic Syndrome (EMS) is defined by several clinical signs including obesity, hyperinsulinemia, and peripheral insulin dysregulation (ID). Affected horses may also exhibit hypertension, hyperlipemia and systemic inflammation. Measures of ID typically comprise the gold-standard for diagnosis in veterinary care. Yet, the dynamic nature of insulin homeostasis and complex procedures of typical assays make accurate quantification of ID and EMS challenging. This work aimed to investigate new strategies for identification of biochemical markers and correlated genes in EMS. To quantify EMS risk within this population, we utilized a composite score derived from nine common diagnostic variables. We applied a global liquid chromatography/mass spectroscopy approach (HPLC/MS) to whole plasma collected from 49 Arabian horses, resulting in 3392 high-confidence features and identification of putative metabolites in public databases. We performed a genome wide association analysis with genotypes from the 670k Affymetrix Equine SNP array utilizing EMS-correlated metabolites as phenotypes. We discovered four metabolite features significantly correlated with EMS score (P < 1.474 × 10^-5). GWAs for these features results (P = 6.787 × 10^-7, Bonferroni) identified four unique candidate regions (r² > 0.4) containing 63 genes. Significant genomic markers capture 43.52% of the variation in the original EMS score phenotype. The identified genomic loci provide insight into the pathways controlling variation in EMS and the origin of genetic predisposition to the condition. Rapid, feasible and accurate diagnostic tools derived from metabogenomics can be translated into measurable benefits in the timeline and quality of preventative management practices to preserve health in horses.

SUBMITTER: Patterson Rosa L

PROVIDER: S-EPMC7494547 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeChronic diseases affecting the inner ear and the retina cause severe impairments to our communication systems. In more than half of the cases, Usher syndrome (USH) is the origin of these double defects. Patients with USH type II (USH2) have retinitis pigmentosa (RP) that develops during puberty, moderate to severe hearing impairment with downsloping pure-tone audiogram, and normal vestibular function. Four loci and three genes are known for USH2. In this study, we proposed to localize the gene responsible for USH2 in a consanguineous family of Tunisian origin.MethodsAffected members underwent detailed ocular and audiologic characterization. One Tunisian family with USH2 and 45 healthy controls unrelated to the family were recruited. Two affected and six unaffected family members attended our study. DNA samples of eight family members were genotyped with polymorphic markers. Two-point and multipoint LOD scores were calculated using Genehunter software v2.1. Sequencing was used to investigate candidate genes.ResultsHaplotype analysis showed no significant linkage to any known USH gene or locus. A genome-wide screen, using microsatellite markers, was performed, allowing the identification of three homozygous regions in chromosomes 2, 4, and 15. We further confirmed and refined these three regions using microsatellite and single-nucleotide polymorphisms. With recessive mode of inheritance, the highest multipoint LOD score of 1.765 was identified for the candidate regions on chromosomes 4 and 15. The chromosome 15 locus is large (55 Mb), underscoring the limited number of meioses in the consanguineous pedigree. Moreover, the linked, homozygous chromosome 15q alleles, unlike those of the chromosome 2 and 4 loci, are infrequent in the local population. Thus, the data strongly suggest that the novel locus for USH2 is likely to reside on 15q.ConclusionsOur data provide a basis for the localization and the identification of a novel gene implicated in USH2, most likely localized on 15q.

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Metabogenomics reveals four candidate regions involved in the pathophysiology of Equine Metabolic Syndrome.

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