OMIA 001897-9796 : Hoof wall separation syndrome in Equus caballus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 615682 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2015

Species-specific name: Also known as Hoof Wall Separation Disease

Species-specific symbol: HWSD

Inheritance: All ponies homozygous for this allele were affected by HWSD suggesting complete penetrance. However, affected ponies have varying levels of disease form mild to severe, indicating variable expressivity. No potential genetic modifiers were found in this study. Heterozygosity for this allele was not a cause for disease (Finno et al., 2015). (FN thanks Daniel J. Schmidt, who provided the basis of this contribution, working under the supervision of Professor Ernie Bailey; 16 April 2020)

Mapping: By conducting a GWAS on 15 affected and 17 non-affected Connemara ponies, each genotyped with the Illumina SNP70 Genotyping Beadchip (yielding 51,453 informative SNPs), Finno et al. (2015) mapped this disorder to a 1.7Mb region on horse chromosome ECA8: 79,936,024–81,676,900 bp; UCSC assembly equCab2.

Molecular basis: Whole-genome next-generation sequencing was conducted on 4 Connemara Ponies (2 cases, 2 control). The variants in the candidate region (see Mapping section above) were evaluated in a larger sample of Connemara Ponies, and a non-synonymous variant within the gene SERPINB11 was identified as the most likely cause of the trait, namely g.83600643_83600644insC (updated to Equcab 3.0) which introduces a frameshift resulting in a premature stop codon (Finno et al., 2015). This variant was homozygous in 23 affected horses and heterozygous in 27 obligate carriers. Evaluation of mRNA levels at the proximal hoof capsule of 8 Connemara ponies (4 cases, 4 controls) showed that SERPINB11 expression was significantly reduced in the affected ponies. (Finno et al., 2015) (FN thanks Daniel J. Schmidt, who provided the basis of this contribution, working under the supervision of Professor Ernie Bailey; 16 April 2020)

Clinical features: Hoof Wall Separation Disease (HWSD) is a disease that affects the Connemara Pony, a breed known for their strong, hearty hooves. HWSD is classified primarily by its clinical signs of a receding dorsal hoof wall and secondary solar proliferation. This disease differs from other causes of separation (e.g. White Line Disease, Abscessation, etc.) because the sole and white line both appear healthy, with the exception of the proliferative sole. (FN thanks Daniel J. Schmidt, who provided the basis of this contribution, working under the supervision of Professor Ernie Bailey; 16 April 2020)

Prevalence: "Within the entire 423-Connemara-pony data set, allele frequency was 18.7% and a total of 96 ponies were heterozygous for the SERPINB11 insertion. The heterozygous animals are all phenotypically unaffected by HWSD. Within a 324-pony subset of individuals unrelated to the affected animals, carrier frequency for the variant is 14.8%." The variant was not found among 169 horses of other unspecified breeds (Finno et al., 2015). (FN thanks Daniel J. Schmidt, who provided the basis of this contribution, working under the supervision of Professor Ernie Bailey; 16 April 2020)

Breed: Connemara pony.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
SERPINB11 serpin peptidase inhibitor, clade B (ovalbumin), member 11 Equus caballus 8 NC_009151.3 (83582594..83604783) SERPINB11 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
965 Connemara pony Hoof wall separation syndrome SERPINB11 insertion, small (<=20) Naturally occurring variant EquCab3.0 8 g.83600643_83600644insC c.504_505insC p.(T169Hfs*3) 2015 25875171 FN thanks Daniel J. Schmidt, working under the supervision of Professor Ernie Bailey, for updating the coordinates to EquCab3.0.

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.
2015 Finno, C.J., Stevens, C., Young, A., Affolter, V., Joshi, N.A., Ramsay, S., Bannasch, D.L. :
SERPINB11 frameshift variant associated with novel hoof specific phenotype in Connemara ponies. PLoS Genet 11:e1005122, 2015. Pubmed reference: 25875171. DOI: 10.1371/journal.pgen.1005122.
2013 Bannasch, D.L., Finno, C.J., Stevens, C., Young, A. , Ramsey, S. :
A successful genome wide association for Connemara Hoof Wall Separation Syndrome using the Equine Illumina 74K Beadchip. 10th Dorothy Russell Havemeyr Foundation International Equine Genome Mapping Workshop, Azores, Portugal. :Abstract p. 132, 2013.

Edit History


  • Created by Carrie Finno on 11 Dec 2013
  • Changed by Carrie Finno on 11 Dec 2013
  • Changed by Carrie Finno on 26 Nov 2014
  • Changed by Frank Nicholas on 21 Apr 2015
  • Changed by Frank Nicholas on 16 Apr 2020