Evaluation of a new variant in the aggrecan gene potentially associated with chondrodysplastic dwarfism in Miniature horses.
Abstract: Chondrodysplastic dwarfism in Miniature horses is an autosomal recessive disorder previously associated with four mutations (D1, D2, D3*, and D4) in the aggrecan (ACAN) gene. The aim of this study was to identify additional variants in the candidate ACAN gene associated with chondrodysplastic dwarfism in Miniature horses. Fifteen dwarf Miniature horses were found to possess only one of the dwarfism-causing variants, and two possessed none of the variants. The ACAN exons (EquCab3.0) of seven dwarf Miniature horses were sequenced. A missense SNP in coding exon 11 (g.95271115A > T, c.6465A > T-RefSeq XM_005602799.2), which resulted in the amino acid substitution p.Leu2155Phe (RefSeq XP_005602856.2), was initially associated with the dwarf phenotype. The variant was tested and found present in 14 dwarf foals as well as one parent of each, and both parents of a dwarf possessing two copies. Genetic testing of 347 phenotypically normal Miniature horses demonstrated that none had more than one of the dwarf alleles or c.6465A > T. However, a study of large breeds revealed the presence of c.6465A > T, which was present in homozygosis in two Mangalarga Marchador horses. We suggest that c.6465A > T as a marker of disequilibrium or complex interactions in the Miniature horse genome could contribute to the associated dwarfism.
Publication Date: 2020-09-17 PubMed ID: 32943661PubMed Central: PMC7499210DOI: 10.1038/s41598-020-72192-3Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study investigates a newly discovered variant in the aggrecan gene that could be linked to chondrodysplastic dwarfism—a genetic disorder leading to abnormal bone development—in Miniature horses. The research involves sequencing the aggrecan gene in afflicted horses, finding the new variant, and suggesting the possibility of complex interactions in the Miniature horse genome contributing to this form of dwarfism.
Introduction to Dwarfism in Miniature Horses
- The research focuses on chondrodysplastic dwarfism in Miniature horses. This is a genetic disorder that leads to abnormal bone and cartilage development and results in dwarf stature.
- Previous studies identified this disorder as an autosomal recessive trait and associated it with four known mutations (D1, D2, D3*, and D4) in the aggrecan gene (ACAN).
Investigation of Additional ACAN Variants
- The aim of this study was to seek and identify additional variants or mutations in the ACAN gene that may contribute to dwarfism in Miniature horses.
- Fifteen dwarf Miniature horses were found with only one of the known dwarfism-causing mutations while two had none of the known variants.
- Researchers sequenced the ACAN exons of seven dwarf Miniature horses and identified a new missense single nucleotide polymorphism (SNP) in coding exon 11.
Identifying a New Variant
- The SNP found was initially linked to dwarf phenotype. This mutation caused an amino acid substitution, which could disrupt the normal functioning of the aggrecan protein.
- Further testing found this mutation in 14 dwarf foals and in at least one parent for each. This suggests the variant is not harmful in a single copy but could potentially cause disease when present in two copies (as an autosomal recessive disorder).
Further Observations and Suggestions
- Genetic testing conducted on 347 phenotypically normal Miniature horses revealed that none of the horses had more than one of the known dwarf alleles or the newly discovered variant.
- Interestingly, the new variant was found in homozygosis (present in two copies) in two large breed horses, specifically the Mangalarga Marchador horses. Thus, the variant alone may not explain the dwarfism.
- Therefore, the researchers suggest that complex interactions in the Miniature horse genome could contribute to the dwarfism phenotype, with the new variant acting as a marker of such genetic disequilibrium.
Cite This Article
APA
de Andrade DGA, Basso RM, Magro AJ, Laufer-Amorim R, Borges AS, de Oliveira-Filho JP.
(2020).
Evaluation of a new variant in the aggrecan gene potentially associated with chondrodysplastic dwarfism in Miniature horses.
Sci Rep, 10(1), 15238.
https://doi.org/10.1038/s41598-020-72192-3 Publication
Researcher Affiliations
- School of Veterinary Medicine and Animal Science, São Paulo State University (Unesp), Botucatu, 18618-681, Brazil.
- School of Veterinary Medicine and Animal Science, São Paulo State University (Unesp), Botucatu, 18618-681, Brazil.
- Institute for Biotechnology, São Paulo State University (Unesp), Botucatu, 18607-440, Brazil.
- School of Agriculture, São Paulo State University (Unesp), Botucatu, 18610-034, Brazil.
- School of Veterinary Medicine and Animal Science, São Paulo State University (Unesp), Botucatu, 18618-681, Brazil.
- School of Veterinary Medicine and Animal Science, São Paulo State University (Unesp), Botucatu, 18618-681, Brazil.
- School of Veterinary Medicine and Animal Science, São Paulo State University (Unesp), Botucatu, 18618-681, Brazil. jose.oliveira-filho@unesp.br.
MeSH Terms
- Aggrecans / genetics
- Animals
- Dwarfism / genetics
- Dwarfism / pathology
- Dwarfism / veterinary
- Female
- Genes, Recessive
- Genetic Markers
- Genetic Variation
- Horse Diseases / genetics
- Horse Diseases / pathology
- Horses / genetics
- Male
- Mutation, Missense
- Osteochondrodysplasias / genetics
- Osteochondrodysplasias / pathology
- Osteochondrodysplasias / veterinary
- Phenotype
- Polymorphism, Single Nucleotide
Conflict of Interest Statement
The authors declare no competing interests.
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