Evaluation of an HMGA2 variant for pleiotropic effects on height and metabolic traits in ponies.
- Journal Article
Summary
The research concludes a specific genetic variant in ponies linked with height, also influences metabolic traits and can contribute to a condition akin to human metabolic syndrome. This finding might help in early identification of horses prone to this metabolic disorder.
Study Methodology and Participants
This research is based on a retrospective study that involved a sample of 294 Welsh ponies and 529 horses. The ponies were assessed for a spectrum of metabolic traits, with a particular focus on insulin function and levels, which can indicate susceptibility to metabolic disorders. In addition, the connection between these metabolic characteristics and the height of the ponies was determined using statistical correlation measures.
Findings on Metabolic Traits and Height
The study discovered a significant negative correlation between the height of the ponies and their base level of insulin, meaning as height increased, insulin levels decreased.
Identification of a Key Genetic Region
A combination of genome-wide analysis tools was used to locate predominant genetic regions affecting both height and associated metabolic traits. A specific ~1.3 megabase region on chromosome 6 was identified, which carried a shared haplotype for the linked traits of height and insulin levels. That means this genetic segment was common in ponies with similar height and metabolic qualities.
Heritability Factors
Notably, this region of interest (ROI) accounted for approximately 40% of the heritability of height and around 20% of the heritability for insulin. This suggests a substantial amount of observed variance in these traits among the ponies can be explained by genetic factors in this ROI.
Relevance of the HMGA2 Variant
The High-mobility group AT-hook 2 (HMGA2) was recognized as a promising candidate gene within this ROI. A specific genetic variant of this gene (c.83G>A (p.G28E)) that affects height was detected to be predominant in the Shetland ponies from the sample.
Correlation with Other Metabolic Traits
In the pony sample, the alternative form of this gene (the ‘A’ allele) was found to have a strong negative correlation with height and showed a moderate positive correlation with other metabolic traits. These include the levels of insulin, insulin response after an oral sugar test, non-esterified fatty acids, and triglyceride concentrations.
Implications of the Study
The study suggests this genomic location and the identified gene variant could be used as potential markers to identify ponies at higher risk of developing equine metabolic syndrome (EMS), similar to metabolic syndrome in humans. The implications of these findings could be substantial, enabling at-risk animals to be identified and treated earlier, potentially improving their health outcomes.
Cite This Article
Publication
Researcher Affiliations
- Veterinary Population Medicine Department, University of Minnesota, St. Paul, Minnesota.
- Veterinary Population Medicine Department, University of Minnesota, St. Paul, Minnesota.
- Veterinary Population Medicine Department, University of Minnesota, St. Paul, Minnesota.
- Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, Minnesota.
- Massey University, College of Sciences, Palmerston North, New Zealand.
- Veterinary Population Medicine Department, University of Minnesota, St. Paul, Minnesota.
MeSH Terms
- Animals
- Biometry
- Fatty Acids, Nonesterified / blood
- Female
- Glucose Tolerance Test / veterinary
- Horse Diseases / genetics
- Horse Diseases / metabolism
- Horses / anatomy & histology
- Horses / genetics
- Insulin / blood
- Insulin Resistance / genetics
- Male
- Metabolic Syndrome / genetics
- Metabolic Syndrome / veterinary
- Phenotype
- Retrospective Studies
- Species Specificity
- Triglycerides / blood
Grant Funding
- T32 OD010993 / Foundation for the National Institutes of Health
- D14EQ-033 / Morris Animal Foundation
- 2009-55205-052542012-67015-19432 / National Institute of Food and Agriculture
Conflict of Interest Statement
References
Citations
This article has been cited 18 times.- Stefaniuk-Szmukier M, Piórkowska K, Ropka-Molik K. Equine Metabolic Syndrome: A Complex Disease Influenced by Multifactorial Genetic Factors. Genes (Basel) 2023 Jul 27;14(8).
- Mousavi SF, Razmkabir M, Rostamzadeh J, Seyedabadi HR, Naboulsi R, Petersen JL, Lindgren G. Genetic diversity and signatures of selection in four indigenous horse breeds of Iran. Heredity (Edinb) 2023 Aug;131(2):96-108.
- Clark BL, Bamford NJ, Stewart AJ, McCue ME, Rendahl A, Bailey SR, Bertin FR, Norton EM. Evaluation of an HMGA2 variant contribution to height and basal insulin concentrations in ponies. J Vet Intern Med 2023 May-Jun;37(3):1186-1192.
- Han H, Randhawa IAS, MacHugh DE, McGivney BA, Katz LM, Dugarjaviin M, Hill EW. Selection signatures for local and regional adaptation in Chinese Mongolian horse breeds reveal candidate genes for hoof health. BMC Genomics 2023 Jan 19;24(1):35.
- Golding E, Neavyn Neita A, Walshe N, Hanlon A, Mulcahy G, Duggan V. Survey of the knowledge and perceptions of horse owners in Ireland of common clinical conditions and their impact. Equine Vet J 2023 Mar;55(2):270-281.
- Durward-Akhurst SA, Schaefer RJ, Grantham B, Carey WK, Mickelson JR, McCue ME. Genetic Variation and the Distribution of Variant Types in the Horse. Front Genet 2021;12:758366.
- Fang J, Zhang D, Cao JW, Zhang L, Liu CX, Xing YP, Wang F, Xu HY, Wang SC, Ling Y, Wang W, Zhang YR, Zhou HM. Pathways involved in pony body size development. BMC Genomics 2021 Jan 18;22(1):58.
- Horn R, Stewart AJ, Jackson KV, Dryburgh EL, Medina-Torres CE, Bertin FR. Clinical implications of using adrenocorticotropic hormone diagnostic cutoffs or reference intervals to diagnose pituitary pars intermedia dysfunction in mature horses. J Vet Intern Med 2021 Jan;35(1):560-570.
- Wallis N, Raffan E. The Genetic Basis of Obesity and Related Metabolic Diseases in Humans and Companion Animals. Genes (Basel) 2020 Nov 20;11(11).
- Carslake HB, Pinchbeck GL, McGowan CM. Equine metabolic syndrome in UK native ponies and cobs is highly prevalent with modifiable risk factors. Equine Vet J 2021 Sep;53(5):923-934.
- Vignali R, Marracci S. HMGA Genes and Proteins in Development and Evolution. Int J Mol Sci 2020 Jan 19;21(2).
- Pu Y, Zhang Y, Zhang T, Han J, Ma Y, Liu X. Identification of Novel lncRNAs Differentially Expressed in Placentas of Chinese Ningqiang Pony and Yili Horse Breeds. Animals (Basel) 2020 Jan 11;10(1).
- Norton E, Schultz N, Geor R, McFarlane D, Mickelson J, McCue M. Genome-Wide Association Analyses of Equine Metabolic Syndrome Phenotypes in Welsh Ponies and Morgan Horses. Genes (Basel) 2019 Nov 6;10(11).
- Raudsepp T, Finno CJ, Bellone RR, Petersen JL. Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post-genome era. Anim Genet 2019 Dec;50(6):569-597.
- Grilz-Seger G, Neuditschko M, Ricard A, Velie B, Lindgren G, Mesarič M, Cotman M, Horna M, Dobretsberger M, Brem G, Druml T. Genome-Wide Homozygosity Patterns and Evidence for Selection in a Set of European and Near Eastern Horse Breeds. Genes (Basel) 2019 Jun 28;10(7).
- Jafari H, Abebe BK, Cong L, Ahmed Z, Zhaofei W, Sun M, Muhatai G, Chuzhao L, Dang R. Review: Genomic insights into the adaptive traits and stress resistance in modern horses. Stress Biol 2026 Jan 12;6(1):5.
- Kingsley NB, Sandmeyer L, Dwyer A, Langefeld CD, McMullen RJ Jr, McCue M, Lassaline M, Bellone RR. A genome-wide investigation of insidious uveitis in Appaloosa horses. BMC Genomics 2025 Oct 9;26(1):904.
- Li T, Jin M, Wang H, Zhang W, Yuan Z, Wei C. Whole-Genome Scanning for Selection Signatures Reveals Candidate Genes Associated with Growth and Tail Length in Sheep. Animals (Basel) 2024 Feb 22;14(5).
