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Mammalian genome : official journal of the International Mammalian Genome Society2016; 28(3-4); 143-151; doi: 10.1007/s00335-016-9673-4

Whole-genome sequencing reveals a potential causal mutation for dwarfism in the Miniature Shetland pony.

Abstract: The Miniature Shetland pony represents a horse breed with an extremely small body size. Clinical examination of a dwarf Miniature Shetland pony revealed a lowered size at the withers, malformed skull and brachygnathia superior. Computed tomography (CT) showed a shortened maxilla and a cleft of the hard and soft palate which protruded into the nasal passage leading to breathing difficulties. Pathological examination confirmed these findings but did not reveal histopathological signs of premature ossification in limbs or cranial sutures. Whole-genome sequencing of this dwarf Miniature Shetland pony and comparative sequence analysis using 26 reference equids from NCBI Sequence Read Archive revealed three probably damaging missense variants which could be exclusively found in the affected foal. Validation of these three missense mutations in 159 control horses from different horse breeds and five donkeys revealed only the aggrecan (ACAN)-associated g.94370258G>C variant as homozygous wild-type in all control samples. The dwarf Miniature Shetland pony had the homozygous mutant genotype C/C of the ACAN:g.94370258G>C variant and the normal parents were heterozygous G/C. An unaffected full sib and 3/5 unaffected half-sibs were heterozygous G/C for the ACAN:g.94370258G>C variant. In summary, we could demonstrate a dwarf phenotype in a miniature pony breed perfectly associated with a missense mutation within the ACAN gene.
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Publication Date: 2016-12-09 PubMed ID: 27942904DOI: 10.1007/s00335-016-9673-4Google 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 article discusses a research study where whole-genome sequencing was used to identify a potential genetic cause for dwarfism in Miniature Shetland ponies. The researchers found a mutation in the aggrecan (ACAN) gene that was significantly associated with the dwarfism phenotype.

Study Subject and Clinical Findings

  • The researchers selected a dwarf Miniature Shetland pony as the subject of this study. The pony showed distinctive features such as a smaller height, a malformed skull, and an upper jaw that was shorter than usual (brachygnathia superior).
  • Additionally, the pony had a cleft in the hard and soft palate, which protruded into the nasal passage and caused breathing difficulties. Computed Tomography (CT) scans were used to confirm these physical abnormalities.
  • However, pathological examination did not show signs of premature ossification (early bone formation) in the limbs or the cranial sutures (parts where skull bones meet). This indicates that the dwarfism was not due to premature closure of the growth plates in the bones.

DNA Sequencing and Analysis

  • In order to identify potential genetic causes for the dwarfism, the researchers conducted whole-genome sequencing on the dwarf pony. In this process, the entire genetic material of the pony was mapped out, allowing the researchers to scrutinize each gene for abnormalities.
  • The sequence was then compared with the genomic sequences of 26 reference equids (horse-like animals) from the NCBI Sequence Read Archive. This comparison revealed three missense variants (changes in DNA that cause a different amino acid to be incorporated during protein synthesis) which were uniquely found in the affected pony. A missense mutation can potentially cause disease if the replaced amino acid alters the function of the protein that gene encodes for.

Gene Mutation Validation

  • To validate the significance of the identified missense mutations, the researchers tested these mutations in 159 control horses from different breeds and five donkeys.
  • Only one mutation, the ACAN gene mutation, was found to be homozygous wild-type (the version of the gene that is common in the general population) in all control samples (none of the control animals had the mutation).
  • The dwarf pony had two copies of the mutant ACAN gene (homozygous), while the parents who were normal had one copy each of the mutant and the normal gene (heterozygous). An unaffected full sibling and three out of five half-siblings also exhibited this heterozygous pattern.
  • The results suggest a perfect association between the ACAN gene mutation and the dwarf phenotype, providing strong evidence that this mutation is the causal factor for dwarfism in this pony breed.

Cite This Article

APA
Metzger J, Gast AC, Schrimpf R, Rau J, Eikelberg D, Beineke A, Hellige M, Distl O. (2016). Whole-genome sequencing reveals a potential causal mutation for dwarfism in the Miniature Shetland pony. Mamm Genome, 28(3-4), 143-151. https://doi.org/10.1007/s00335-016-9673-4

Publication

Mammalian genome : official journal of the International Mammalian Genome Society
ISSN: 1432-1777
NlmUniqueID: 9100916
Country: United States
Language: English
Volume: 28
Issue: 3-4
Pages: 143-151

Researcher Affiliations

Metzger, Julia
  • Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.
Gast, Alana Christina
  • Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.
Schrimpf, Rahel
  • Unit of Reproductive Medicine of the Clinics, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.
Rau, Janina
  • Unit of Reproductive Medicine of the Clinics, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.
Eikelberg, Deborah
  • Department of Pathology, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.
Beineke, Andreas
  • Department of Pathology, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.
Hellige, Maren
  • Clinic for Horses, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.
Distl, Ottmar
  • Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, 30559, Hannover, Germany. ottmar.distl@tiho-hannover.de.

MeSH Terms

  • Aggrecans / genetics
  • Animals
  • Breeding
  • Dwarfism / genetics
  • Dwarfism / physiopathology
  • Genotype
  • Homozygote
  • Horse Diseases / genetics
  • Horse Diseases / physiopathology
  • Horses / genetics
  • Horses / growth & development
  • Mutation, Missense / genetics
  • Phenotype
  • Whole Genome Sequencing

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Citations

This article has been cited 7 times.
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