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PloS one2015; 10(10); e0140749; doi: 10.1371/journal.pone.0140749

A Non-Synonymous HMGA2 Variant Decreases Height in Shetland Ponies and Other Small Horses.

Abstract: The identification of quantitative trait loci (QTL) such as height and their underlying causative variants is still challenging and often requires large sample sizes. In humans hundreds of loci with small effects control the heritable portion of height variability. In domestic animals, typically only a few loci with comparatively large effects explain a major fraction of the heritability. We investigated height at withers in Shetland ponies and mapped a QTL to ECA 6 by genome-wide association (GWAS) using a small cohort of only 48 animals and the Illumina equine SNP70 BeadChip. Fine-mapping revealed a shared haplotype block of 793 kb in small Shetland ponies. The HMGA2 gene, known to be associated with height in horses and many other species, was located in the associated haplotype. After closing a gap in the equine reference genome we identified a non-synonymous variant in the first exon of HMGA2 in small Shetland ponies. The variant was predicted to affect the functionally important first AT-hook DNA binding domain of the HMGA2 protein (c.83G>A; p.G28E). We assessed the functional impact and found impaired DNA binding of a peptide with the mutant sequence in an electrophoretic mobility shift assay. This suggests that the HMGA2 variant also affects DNA binding in vivo and thus leads to reduced growth and a smaller stature in Shetland ponies. The identified HMGA2 variant also segregates in several other pony breeds but was not found in regular-sized horse breeds. We therefore conclude that we identified a quantitative trait nucleotide for height in horses.
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Publication Date: 2015-10-16 PubMed ID: 26474182PubMed Central: PMC4608717DOI: 10.1371/journal.pone.0140749Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article explores an identified quantitative trait locus (loci when plural) that affects height in Shetland ponies and similar small horse breeds. The study discovered a height-related variant in the HMGA2 gene, which might limit growth and cause a smaller stature.

Methodology and Findings

  • This study investigated the impact of quantitative trait loci (QTL) on height by focusing on Shetland ponies. QTL are regions of the genome where variation directly influences observable traits.
  • Through genome-wide association analysis (GWAS) of a small group of 48 ponies, a QTL impacting height was found on the ECA 6 gene.
  • Fine mapping of the identified location showed a shared haplotype block (a set of DNA variations likely to be inherited together) of 793 kilobases in the smaller ponies.
  • The HMGA2 gene, which is known to influence height in various species, was located within the associated haplotype.

The HMGA2 Gene Variant and Its Impact

  • After filling a gap in the equine reference genome (a standard genetic sequence), a non-synonymous change in the first exon (a section of a gene that codes for proteins) of the HMGA2 gene was found in smaller Shetland ponies.
  • This variant was predicted to affect the AT-hook DNA binding domain of the HMGA2 protein, a region important for gene modulation.
  • Functional assessment of this variant revealed that its presence impedes the DNA binding process, which is validated by results from an electrophoretic mobility shift assay (a method for studying protein-DNA interaction).
  • It’s suggested that this impairment results in hindered growth and smaller stature in Shetland ponies.

Applicability of the Study’s Findings

  • The identified HMGA2 variant was also found present in several other pony breeds but was not detected in regular-sized horse breeds.
  • Thus, it is concluded that the identified variant is a significant quantitative trait nucleotide (a single base pair’s impact on a trait) for height in horses.

Cite This Article

APA
Frischknecht M, Jagannathan V, Plattet P, Neuditschko M, Signer-Hasler H, Bachmann I, Pacholewska A, Drögemüller C, Dietschi E, Flury C, Rieder S, Leeb T. (2015). A Non-Synonymous HMGA2 Variant Decreases Height in Shetland Ponies and Other Small Horses. PLoS One, 10(10), e0140749. https://doi.org/10.1371/journal.pone.0140749

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 10
Issue: 10
Pages: e0140749
PII: e0140749

Researcher Affiliations

Frischknecht, Mirjam
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland; Agroscope, Swiss National Stud Farm, 1580, Avenches, Switzerland; Swiss Competence Center of Animal Breeding and Genetics, University of Bern, Bern University of Applied Sciences HAFL & Agroscope, 3001, Bern, Switzerland.
Jagannathan, Vidhya
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland; Swiss Competence Center of Animal Breeding and Genetics, University of Bern, Bern University of Applied Sciences HAFL & Agroscope, 3001, Bern, Switzerland.
Plattet, Philippe
  • Division of Experimental and Clinical Research, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland.
Neuditschko, Markus
  • Agroscope, Swiss National Stud Farm, 1580, Avenches, Switzerland; Swiss Competence Center of Animal Breeding and Genetics, University of Bern, Bern University of Applied Sciences HAFL & Agroscope, 3001, Bern, Switzerland.
Signer-Hasler, Heidi
  • Swiss Competence Center of Animal Breeding and Genetics, University of Bern, Bern University of Applied Sciences HAFL & Agroscope, 3001, Bern, Switzerland; Bern University of Applied Sciences, School of Agricultural, Forest and Food Sciences, 3052, Zollikofen, Switzerland.
Bachmann, Iris
  • Agroscope, Swiss National Stud Farm, 1580, Avenches, Switzerland.
Pacholewska, Alicja
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland; Swiss Competence Center of Animal Breeding and Genetics, University of Bern, Bern University of Applied Sciences HAFL & Agroscope, 3001, Bern, Switzerland; Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, 3001, Bern, Switzerland.
Drögemüller, Cord
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland; Swiss Competence Center of Animal Breeding and Genetics, University of Bern, Bern University of Applied Sciences HAFL & Agroscope, 3001, Bern, Switzerland.
Dietschi, Elisabeth
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland; Swiss Competence Center of Animal Breeding and Genetics, University of Bern, Bern University of Applied Sciences HAFL & Agroscope, 3001, Bern, Switzerland.
Flury, Christine
  • Swiss Competence Center of Animal Breeding and Genetics, University of Bern, Bern University of Applied Sciences HAFL & Agroscope, 3001, Bern, Switzerland; Division of Experimental and Clinical Research, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland.
Rieder, Stefan
  • Agroscope, Swiss National Stud Farm, 1580, Avenches, Switzerland; Swiss Competence Center of Animal Breeding and Genetics, University of Bern, Bern University of Applied Sciences HAFL & Agroscope, 3001, Bern, Switzerland.
Leeb, Tosso
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland; Swiss Competence Center of Animal Breeding and Genetics, University of Bern, Bern University of Applied Sciences HAFL & Agroscope, 3001, Bern, Switzerland.

MeSH Terms

  • Animals
  • Exons
  • HMGA2 Protein / genetics
  • Horses / genetics
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Switzerland

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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