Evaluation of a new variant in the aggrecan gene potentially associated with chondrodysplastic dwarfism in Miniature horses

Author(s)

Abranches de Andrade, Danilo Giorgi ^[1] ; Basso, Roberta Martins ^[1] ; Magro, Angelo Jose ^{[2, 3]} ; Laufer-Amorim, Renee ^[1] ; Borges, Alexandre Secorun ^[1] ; de Oliveira-Filho, Jose Paes ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Vet Med & Anim Sci, BR-18618681 Botucatu, SP - Brazil

^[2] Sao Paulo State Univ Unesp, Inst Biotechnol, BR-18607440 Botucatu, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Sch Agr, BR-18610034 Botucatu, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 SEP 17 2020.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 16/24025-0 - Evaluation of causative mutations of chondrodysplasia-like dwarfism in the Miniature Horse in Brazil
• Grantee: Danilo Giorgi Abranches de Andrade
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/11365-3 - Study of the aggrecan protein and cytokine pattern associated with dwarfism in Mini-horse breed in Brazil
• Grantee: Roberta Martins Basso
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/24767-7 - Clinical and molecular study of chondrodysplasia-like dwarfism in the Miniature Horse in Brazil
• Grantee: José Paes de Oliveira Filho
• Support Opportunities: Regular Research Grants