OMIA 002068-9796 : Dwarfism, Friesian in Equus caballus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 130070

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2016

History: Back et al. (2008) reported six disproportionate dwarfs in the Friesian breed.

Mapping: By conducting a GWAS on 10 affected and 10 normal Friesian horses, each genotyped with the equine SNP50 chip (yielding 34,429 informative SNPs), Orr et al. (2010) mapped this disorder to a 2Mb region of chromosome ECA14.

Via an independent GWAS involving 19 Friesian dwarfs and 65 non-affected Friesian controls, each genotyped with the Illumina® EquineSNP50 Genotyping BeadChip (yielding 29,840 informative SNPs), Leegwater et al. (2016) confirmed this location, specifying the region as "between positions 3151847 and 6229282 on ECA14".

Molecular basis: By comparing genomic sequence in the candidate region from 4 dwarf Friesians, 3 non-affected Friesian controls, the horse reference genome and a Quarter Horse (a breed in which dwarfism has not been reported), Leegwater et al. (2016) identified a likely causal (missense) variant in Friesians as g.4535550C>T; c.50G>A; p.Arg17Lys in B4GALT7. The point mutation concerns the last nucleotide of exon 1 and Leegwater et al. (2016) demonstrate that it leads to a splicing deficiency of B4GALT7 transcripts. Consistent with the variant being causal, Leegwater et al. (2016) reported that "All 29 dwarfs of which DNA was available were homozygous for the mutation . . . . The 8 obligate carriers were heterozygous . . . and of a group of 177 Friesian horses 22 were carrier of the mutation and 155 were homozygous for the reference allele".

Clinical features: As summarised by Orr et al. (2010), "the Friesian dwarf phenotype results from physeal growth retardation in both limbs and ribs, reflected in a characteristic disproportional growth disturbance. The potential for post-natal growth in these animals, albeit at a reduced rate, is responsible for mature dwarfs having a head of the same size as unaffected animals, a broader chest with narrowing at the costochondral junction, a disproportionally long back and abnormally short limbs. Furthermore, radiographs reveal a dysplastic metaphysis of the distal metacarpus and metatarsus. Light microscopy of growth plates at the costochondral junction demonstrates an irregular transition from cartilage to bone, and thickening and disturbed formation of chondrocyte columns, which is similar to findings in osteochondrodysplasia".

Breed: Friesian.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
B4GALT7 xylosylprotein beta 1,4-galactosyltransferase, polypeptide 7 Equus caballus 14 NC_009157.3 (3772752..3762834) B4GALT7 Homologene, Ensembl, NCBI gene

Variants

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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
Friesian Dwarfism, Friesian B4GALT7 splicing EquCab2 14 g.4535550C>T c.50G>A p.R17K 2016 27793082 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

References


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.
2016 Leegwater, P.A., Vos-Loohuis, M., Ducro, B.J., Boegheim, I.J., van Steenbeek, F.G., Nijman, I.J., Monroe, G.R., Bastiaansen, J.W., Dibbits, B.W., van de Goor, L.H., Hellinga, I., Back, W., Schurink, A. :
Dwarfism with joint laxity in Friesian horses is associated with a splice site mutation in B4GALT7. BMC Genomics 17:839, 2016. Pubmed reference: 27793082. DOI: 10.1186/s12864-016-3186-0.
2010 Orr, N., Back, W., Gu, J., Leegwater, P., Govindarajan, P., Conroy, J., Ducro, B., van Arendonk, JA., MacHugh, DE., Ennis, S., Hill, EW., Brama, PA. :
Genome-wide SNP association-based localization of a dwarfism gene in Friesian dwarf horses. Anim Genet 41 Suppl 2:2-7, 2010. Pubmed reference: 21070269. DOI: 10.1111/j.1365-2052.2010.02091.x.
2009 de Graaf-Roelfsema, E., Back, W., Keizer, HA., Stout, TA., van der Kolk, JH. :
Normal function of the hypothalamic-pituitary growth axis in three dwarf Friesian foals. Vet Rec 165:373-6, 2009. Pubmed reference: 19783851.
2008 Back, W., van der Lugt, J.J., Nikkels, P.G., van den Belt, A.J., van der Kolk, J.H., Stout, T.A. :
Phenotypic diagnosis of dwarfism in six Friesian horses. Equine Vet J 40:282-7, 2008. Pubmed reference: 18267883. DOI: 10.2746/042516408X278201.
2000 Osinga, A. :
Het Fokken van het Friese Paard [Breeding of the Friesian horse]. Schaafsma & Brouwer, Dokkum :, 2000.

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  • Created by Frank Nicholas on 31 Oct 2016
  • Changed by Frank Nicholas on 31 Oct 2016