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Identification of Genetic Loci Underlying Equine Metabolic Syndrome and Laminitis Risk
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Identification of Genetic Loci Underlying Equine Metabolic Syndrome and Laminitis Risk. |
| 개인저자 | Norton, Elaine M. |
| 단체저자명 | University of Minnesota. Comparative and Molecular Biosciences. |
| 발행사항 | [S.l.]: University of Minnesota., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 355 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-06B. Dissertation Abstract International |
| ISBN | 9781392555897 |
| 학위논문주기 | Thesis (Ph.D.)--University of Minnesota, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
Advisor: McCue, Molly E. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Laminitis is a painful, debilitating disease of the hoof, often resulting in these horses being humanely euthanized due to uncontrolled pain. The most commonly cited cause of this life-threatening disease is a clustering of clinical signs resulting from a metabolically efficient phenotype, termed equine metabolic syndrome (EMS). While EMS is a commonly diagnosed syndrome, knowledge of the underlining pathophysiology is lacking and recommendations for diagnostic criteria are vague and inconsistent. EMS is thought to be complex disease, and identification of its underlying genetic risk factors and key gene-by-environment interactions will improve our understanding of EMS pathophysiology and allow for early detection of high-risk individuals and intervention prior to the onset of laminitis. We hypothesized that major genetic risk factors leading to EMS and laminitis susceptibility are shared across breeds of horses, and that differences in the severity and secondary features of the EMS phenotype between breeds, or between individuals within a breed, are the result of modifying genetic risk alleles with variable frequencies between breeds.To test these hypotheses, my PhD thesis has consisted of using phenotype and genotype data on 286 Morgan horses and 264 Welsh ponies, two high risk breeds for EMS. Phenotype data collected on all horses included: signalment, medical history, laminitis status, environmental management (feed, supplements, turnout and exercise regimen), and morphometric measurements (body condition score (BCS), wither height, and neck and girth circumference). After an eight hour fast, an oral sugar test (OST) was performed using 0.15mg/kg Karo lite corn syrup. Biochemical measurements included baseline insulin, glucose, non-esterified fatty acids (NEFA), triglycerides (TG), adiponectin, leptin and ACTH |
| 요약 | Genomic signature of selection analysis was performed using a di statistic and identified a ~1.3 megabase region on chromosome 6, that was also identified on GWA. Haplotype analysis using HapQTL confirmed that there was a shared ancestral haplotype between height and insulin. This region contributed ~40% of the heritability for height and ~20% of the heritability for insulin. HMGA2 was identified as a candidate gene, and sequencing identified a single a c.83G>A variant (p.G28E) in HMGA2, previously described in other small stature horse breeds. In our cohort of ponies, the A allele had a frequency of .76, was strongly correlated with height (-.75) and was low to moderately correlated with metabolic traits including: insulin (.32), insulin after an oral sugar test (.25), non-esterified fatty acids (.19) and triglyceride (.22) concentrations. For this allele, model analysis suggested an additive mode of inheritance with height and a recessive mode of inheritance with the metabolic traits. This was the first gene identified as having a pleotropic effect for EMS.In conclusion, the results of my thesis are major steps forward in understanding the genetic contributions of EMS in two high risk breeds. Future directions include the continued identification of the specific genes and alleles contributing to EMS and could include prioritization of the positional candidate genes identified in aim 2 via (1) identification of biological candidate genes based on known gene function and evidence from other species |
| 일반주제명 | Genetics. Endocrinology. |
| 언어 | 영어 |
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