Multiple alleles of ACAN associated with chondrodysplastic dwarfism in Miniature horses. (30th July 2018)

• Record Type: Journal Article
• Authors: Eberth, J. E.; Graves, K. T.; MacLeod, J. N.; Bailey, E.
• Is Part Of: Animal genetics. Volume 49:Number 5(2018)
• Page Start: 413
• Page End: 420
• Publication Date: 2018-07-30
• Subjects: equine -- exonic variation -- recessive disease -- teratology; Animal genetics -- Periodicals; 572.8
• DOI: 10.1111/age.12682
• Languages: English
• ISSNs: 0268-9146

Abstract

Summary: Chondrodysplastic dwarfism in Miniature horses appeared to be a recessive genetic trait based on the occurrence of affected offspring by normal parents. Dwarf phenotypes vary and range from abnormal abortuses to viable offspring with evidence of skeletal dysplasia. A genome‐wide association study implicated a region of ECA1 with dwarfism in Miniature horses. Aggrecan ( ACAN ) was a candidate gene in that region, and exons were sequenced to compare DNA sequences for dwarf and non‐dwarf horses. Sequencing led to the discovery of variants in exons 2, 6, 7 and 15 associated with dwarfism. The four variants are identified with reference to Ecab 3.0 (GCF_002863925.1) as g.95291270del (rs1095048841), g.95284530C>T (ERP107353), g.95282140C>G (rs1095048823) and g.95257480_95257500del (rs1095048839) and designated here as D1, D2, D3* and D4 respectively. A previous study at another laboratory reported dwarfism associated with homozygosity for D3* . Homozygotes for those variants and compound heterozygotes for any combination of those variants always expressed a dwarfism phenotype. However, eight additional horses with dwarfism were found, seven of which were heterozygotes for D2, D3* or D4, suggesting the existence of additional ACAN alleles causing dwarfism. Among Miniature horses, the combined frequency of D1, D2, D3* and D4 was 0.163, suggesting a carrier rate of 26.2% for alleles causing chondrodysplastic dwarfism.