OMIA 002133-9615 : Skeletal dysplasia, FGF4-retrogene-related in Canis lupus familiaris |
Mendelian trait/disorder:
unknown
Considered a defect:
yes
Year key variant first reported:
2017
Cross-species summary:
A form of disproportionate dwarfism, characterized by short limbs
Mapping:
Brown et al. (2017) reported that a "genome-wide association analysis in a cohort of Nova Scotia duck tolling retrievers (NSDTRs) with and without severe SD identified a significant association on CFA12 due to a 12-Mb associated haplotype, of which 1.9 Mb was found to be shared in chondrodystrophoid breeds."
Molecular basis:
Brown et al. (2017): an FGF4 retrogene insertion in chromosome CFA12 (12: g.33710178_33710179insMF040221.1; CanFam3) is "responsible for SD [skeletal dysplasia] in NSDTR [Nova Scotia Duck Tolling retrievers] . . . the insertion on CFA12 is 3,209 bp long (GenBank accession no. MF040221) and includes parental FGF4 cDNA (i.e., FGF4 exons spliced without introns) . . . . The insert also contains a majority of the predicted 5′-untranslated region (UTR), which includes the transcription start site (TSS) as only PCR primers FGF4_TSS.F1 and FGF4.R1 yielded a product in RT-PCR using cDNA from neonatal beagle IVD . . . . The insertion location is intergenic between the 3′-UTR of OGFRL1 ∼9.5 kb on the proximal side and ∼350 kb to the RIMS1 gene on the distal side." Because the retrogene is not included in NCBI's Gene database, the table below lists the normal FGF4 gene.
Clinical features:
Brown et al. (2017): "Relative to the unaffected dog, the mildly SD-affected NSDTR has cranial bowing of the radius. Radiographic changes in the more severely SD-affected NSDTR include moderate cranial bowing of the radius, physeal widening, and incongruity of the elbow joint with the shape of the semilunar notch of the ulna being elongated."
Breed:
Nova Scotia Duck Tolling retriever.
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| FGF4 | fibroblast growth factor 4 | Canis lupus familiaris | 18 | NC_006600.3 (48413480..48417494) | FGF4 | 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.
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Nova Scotia Duck Tolling retriever | Skeletal dysplasia, FGF4-retrogene-related | FGF4 | insertion, gross (>20) | CanFam 3 | 12 | g.33710178_33710179insMF040221 | " the insertion on CFA12 is 3,209 bp long (GenBank accession no. MF040221) and includes parental FGF4 cDNA (i.e., FGF4 exons spliced without introns) . . . ." | 2017 | 29073074 |
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.
| 2017 | Brown, E.A., Dickinson, P.J., Mansour, T., Sturges, B.K., Aguilar, M., Young, A.E., Korff, C., Lind, J., Ettinger, C.L., Varon, S., Pollard, R., Brown, C.T., Raudsepp, T., Bannasch, D.L. : | |
| FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. Proc Natl Acad Sci U S A 114:11476-11481, 2017. Pubmed reference: 29073074. DOI: 10.1073/pnas.1709082114. | ||
| 1975 | Braund, K.G., Ghosh, P., Taylor, T.K.F., Larsen, L.H. : | |
| Morphological studies of the canine intervertebral disc: the assignment of the Beagle to the achondroplastic classification Research in Veterinary Science 19:167-172, 1975. Pubmed reference: 1166121. |
Edit History
- Created by Frank Nicholas on 25 Oct 2017
- Changed by Frank Nicholas on 25 Oct 2017
- Changed by Frank Nicholas on 26 Oct 2017
- Changed by Frank Nicholas on 23 Jan 2018