OMIA 002068-9796 : Dwarfism, Friesian in Equus caballus

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 130070 (trait) , 604327 (gene)

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.

Inheritance: 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 . . . [and] The 8 obligate carriers were heterozygous". (FN thanks Elizabeth Huffman, who substantially enhanced this section, working under the supervision of Professor Ernie Bailey; 23 April 2020)

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 (3.8–5.4 MB; EquCab2.0) of chromosome ECA14.

Leegwater et al. (2016) mapped this disorder to a similar, slightly-larger region of 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), specifying the region as "between positions 3151847 and 6229282 on ECA14" (Equcab 2.0). (FN thanks Elizabeth Huffman, who substantially enhanced this section, working under the supervision of Professor Ernie Bailey; 23 April 2020)

Molecular basis: Whole genome sequencing was conducted on 4 dwarf Friesians and 3 non-affected Friesian controls, and the resultant sequences were compared in the candidate region with sequence from the horse reference genome and a Quarter Horse (a breed in which dwarfism has not been reported) (Leegwater et al., 2016). The authors 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. (FN thanks Elizabeth Huffman, who substantially enhanced this section, working under the supervision of Professor Ernie Bailey; 23 April 2020)

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".

Prevalence: 177 Friesian horses were tested, with discovery of 22 carriers and 155 homozygotes for the reference allele. Not tested in other breeds. (Leegwater et al., 2016). (FN thanks Elizabeth Huffman, who substantially enhanced this section, working under the supervision of Professor Ernie Bailey; 23 April 2020)

Breed: Friesian horse.

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

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
421 Friesian horse Dwarfism, Friesian B4GALT7 splicing Naturally occurring variant EquCab3.0 14 g.3772591C>T c.50G>A p.(R17K) 2016 27793082 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool. FN thanks Elizabeth Huffman, who updated the g. coordinates to EquCab3, working under the supervision of Professor Ernie Bailey; 23 April 2020.

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.
2021 Vroman, R., Malfait, A.M., Miller, R.E., Malfait, F., Syx, D. :
Animal models of Ehlers-Danlos syndromes: Phenotype, pathogenesis, and translational potential. Front Genet 12:726474, 2021. Pubmed reference: 34712265. DOI: 10.3389/fgene.2021.726474.
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.

Edit History


  • Created by Frank Nicholas on 31 Oct 2016
  • Changed by Frank Nicholas on 31 Oct 2016
  • Changed by Frank Nicholas on 23 Apr 2020
  • Changed by Imke Tammen2 on 17 Aug 2021
  • Changed by Imke Tammen2 on 02 Nov 2021