OMIA 001271-9796 : Dwarfism, ACAN-related in Equus caballus

In other species: cattle

Possibly relevant human trait(s) and/or gene(s) (MIM number): 612813

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Incompletely Dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2017

Mapping: By conducting a GWAS on 20 dwarf and 26 control Miniature horses, each of which had been genotyped with the Illumina Equine SNP50 chip (yielding 40,368 informative SNPs), Eberth (2013) mapped this disorder to a region on chromosome ECA1.

Molecular basis: Noting that the relevant region of chromosome ECA1 contains the ACAN gene that has been implicated in similar types of dwarfism in cattle (see OMIA 001271-9913) and humans (see MIM entry above), Eberth (2013) sequenced this comparative positional candidate gene in affected and normal horses, revealing four variants strongly associated with dwarfism: c.245del, p.K82fx in exon 2 (Acan-D1); c.1270G>A, p.V424M in exon 6 (Acan-D2); c.6700delC, p.P1875fx in exon 11 (Acan-D3); c.7299-7319del, p.F2433-O2440del in exon 15 (Acan-D4).

Bailey (2014) mentioned Eberth's discovery, but made no mention of any specific likely causal variant.

Metzger et al. (2017) reported a missense mutation (g.94370258G>C; p.A505P) as a likely causal variant in Miniature Shetlands.

Eberth's 2013 thesis results were published by Eberth et al. (2018), who reported four likely causal variants, namely "g.95291270del (rs1095048841), g.95284530C>T (ERP107353), g.95282140C>G (rs1095048823) and g.95257480_95257500del (rs1095048839)", all with respect to Ecab 3.0 (GCF_002863925.1), naming them D1, D2, D3*, and D4, respectively. As these authors noted, D3* is the same variant reported by Metzger et al. (2017). As explained by Eberth et al. (2018), D3* is given an asterisk to differentiate it from the original D3 allele described by Eberth (2013), a deletion in exon 11, which turned out to be a technical artifact. Ebert et al. (2018) reported that "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."

Prevalence: Eberth et al. (2018) reported that "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."

Breed: Miniature Shetland.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ACAN aggrecan Equus caballus 1 NC_009144.3 (95320479..95255524) ACAN Homologene, Ensembl, NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Miniature Dwarfism, ACAN-related ACAN D4 deletion, small (<=20) Ecab 3.0 1 g.95257458_95257500del p.Phe2017–Asp2023del rs1095048839 2018 30058072
Miniature Shetland Dwarfism, ACAN-related ACAN D3* missense Ecab 3.0 1 g.95282140C>G p.A505P This variant was named D3* by Eberth et al. (2018) rs1095048823 2017 27942904 Variant coordinates obtained from Eberth et al. (2018)
Miniature Dwarfism, ACAN-related ACAN D2 missense Ecab 3.0 1 g.95284530C>T p.Val424Met 2018 30058072
Miniature Dwarfism, ACAN-related ACAN D1 deletion, small (<=20) Ecab 3.0 1 g.95291270del p.Lys82fx rs1095048841 2018 30058072


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2018 Eberth, J.E., Graves, K.T., MacLeod, J.N., Bailey, E. :
Multiple alleles of ACAN associated with chondrodysplastic dwarfism in Miniature horses. Anim Genet :, 2018. Pubmed reference: 30058072. DOI: 10.1111/age.12682.
2017 Metzger, J., Gast, A.C., Schrimpf, R., Rau, J., Eikelberg, D., Beineke, A., Hellige, M., Distl, O. :
Whole-genome sequencing reveals a potential causal mutation for dwarfism in the Miniature Shetland pony. Mamm Genome 28:143-151, 2017. Pubmed reference: 27942904. DOI: 10.1007/s00335-016-9673-4.
2014 Bailey, E. :
Five things equine veterinarians should know about genomics. Equine Vet J 46:404-7, 2014. Pubmed reference: 24909654. DOI: 10.1111/evj.12271.
2013 Eberth, J.E. :
Chondrodysplasia-Like Dwarfism in the Miniature Horse. Theses and Dissertations--Veterinary Science. Paper 11. Entire thesis is available at, 2013.
2009 Eberth, J., Swerczak, T. , Bailey, E. :
Investigation of dwarfism Among Miniature Horses using the Illumina Horse SNP50 Bead Chip. Journal of Equine Veterinary Science 29:315 only, 2009.

Edit History

  • Created by Frank Nicholas on 27 Jun 2014
  • Changed by Frank Nicholas on 27 Jun 2014
  • Changed by Frank Nicholas on 16 Oct 2014
  • Changed by Frank Nicholas on 11 Aug 2017
  • Changed by Frank Nicholas on 03 Aug 2018