OMIA:001271-9913 : Dwarfism, ACAN-related in Bos taurus (taurine cattle) |
In other species: horse , indicine cattle (zebu)
Categories: Skeleton phene (incl. short stature & teeth)
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 612813 (trait) , 165800 (trait) , 608361 (trait) , 155760 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal incomplete dominant
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2007
Species-specific name: Bulldog calf
Species-specific description: Information about ACAN related dwarfism in Bos indicus cattle was previously listed here and was moved to 'OMIA:001271-9915 : Dwarfism, ACAN-related in Bos indicus' [19/06/2023]
History: As summarised by Cavanagh et al. (2007): "A form of dwarfism (known as bulldog dwarfism) . . . was clearly documented in Dexter cattle in the 19th century (Curran 1990), and its Mendelian inheritance was suspected and discussed as early as 1904 (Seligmann, 1904)." Seligmann's (1904) paper mentions that "the College of Surgeons possesses a complete skeleton of a typical [Dexter bulldog] calf . . . (Teratological Series, 183A)". The citation is actually to an interleaved addendum (A) to entry 183 on page 56 of Lownes and Masters' (1893) catalogue of specimens held by the Royal College of Surgeons. The interleaved addendum comprises an entry from the Royal College's 1894 annual report with hand-written notes. The specimen's catalogue ID in the Royal College of Surgeons' collection is RCSPC/T 16D.11, where it is listed as "Congenital Lethal Chondrodysplasia", having been donated by the Royal Veterinary College in 1894. Seligmann's (1904) paper includes 15 plates illustrating various aspects of Dexter bulldog calves. Calves with this characteristic embryonic-lethal phenotype were described in the Jersey breed by Mead et al. (1946).
Molecular basis: After homozygosity mapping in candidate regions, mutation screening in the aggrecan (ACAN) gene "revealed a 4-bp insertion in exon 11 (2266-2267insGGCA) (called BD1 for diagnostic testing) and a second, rarer transition in exon 1 (-198C>T) (called BD2) that cosegregate with the disorder" (Cavanagh et al., 2007). Cabrera et al. (2016) reported a still-born calf with "Grossly evident chondrodystrophic dwarfism with hydrocephalus, compatible with so-called bulldog calf malformation", the result of a mating between a miniature Scottish Highland bull and cow, each of which was shown to be heterozygous for the same BD1 mutation in ACAN reported by Cavanagh et al. (2007) as being causal of bulldog dwarfism in the Dexter breed. Struck et al. (2018) reported a different likely causal variant (ACAN:c.5686insC; p.Val1898fsTer9), homozygosity for which results in a very similar type of dwarfism in the Miniature Zebu breed: the variant was "homozygous in the affected calf and heterozygous in its [Miniature Zebu] parents". See 'OMIA:001271-9915 : Dwarfism, ACAN-related in Bos indicus' for details.
Genetic engineering:
Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: As summarised by Cavanagh et al. (2007): "Affected fetuses display extremely disproportionate dwarfism, a short vertebral column, marked micromelia, a large abdominal hernia, and a relatively large head with a retruded muzzle, cleft palate, and protruding tongue (Harper et al. 1998)"
Breeds:
Dexter (Cattle) (VBO_0000193),
Jersey (Cattle) (VBO_0000250),
Miniature Highland, United Kingdom of Great Britain and Northern Ireland (Cattle) (VBO_0016855).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| ACAN | aggrecan | Bos taurus | 21 | NC_037348.1 (20377694..20447099) | ACAN | Homologene, Ensembl , NCBI gene |
Variants
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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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 429 | Dexter (Cattle) | Bulldog calf | ACAN | BD2 | regulatory | Naturally occurring variant | ARS-UCD1.2 | 21 | g.20377856C>T | c.-198C>T | rs3423095877 | 2007 | 17952705 | Variant information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170) | |||
| 590 | Dexter (Cattle) Highland (Cattle) | Bulldog calf | ACAN | BD1 | insertion, small (<=20) | Naturally occurring variant | ARS-UCD1.2 | 21 | g.20422104_20422105insGGCA | c.2266_2267insGGCA | Variant initially identified in Dexter cattle and later reported in additional breeds: PMID:26885599 | 2007 | 17952705 | Variant information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170) |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:001271-9913: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
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.
| 2018 | Struck, A.K., Dierks, C., Braun, M., Hellige, M., Wagner, A., Oelmaier, B., Beineke, A., Metzger, J., Distl, O. : |
| A recessive lethal chondrodysplasia in a miniature zebu family results from an insertion affecting the chondroitin sulfat domain of aggrecan. BMC Genet 19:91, 2018. Pubmed reference: 30305023. DOI: 10.1186/s12863-018-0678-8. | |
| 2017 | Dittmer, K.E., Thompson, K.G., Hogan, T. : |
| Severe generalised chondrodysplasia in miniature cattle breeds. N Z Vet J 65:282-283, 2017. Pubmed reference: 28504055. DOI: 10.1080/00480169.2017.1329036. | |
| 2016 | Catalina Cabrera, L., McNabb, B.R., Woods, S.E., Cartoceti, A.N., Busch, R.C. : |
| Hydrops associated with chondrodysplasia of the fetus in a miniature Scottish Highland cow. J Am Vet Med Assoc 248:552-6, 2016. Pubmed reference: 26885599. DOI: 10.2460/javma.248.5.552. | |
| 2007 | Cavanagh, JA., Tammen, I., Windsor, PA., Bateman, JF., Savarirayan, R., Nicholas, FW., Raadsma, HW. : |
| Bulldog dwarfism in Dexter cattle is caused by mutations in ACAN. Mamm Genome 18:808-814, 2007. Pubmed reference: 17952705. DOI: 10.1007/s00335-007-9066-9. | |
| 2006 | Windsor, PA., Cavanagh, JA., Tammen, I. : |
| Hydrops fetalis associated with pulmonary hypoplasia in Dexter calves. Aust Vet J 84:278-81, 2006. Pubmed reference: 16911227. DOI: 10.1111/j.1751-0813.2006.00018.x. | |
| 2005 | Cavanagh, J.A., Tammen, I., Hayden, M.J., Gill, C.A., Nicholas, F.W., Raadsma, H.W. : |
| Characterization of the bovine aggrecan gene: genomic structure and physical and linkage mapping. Anim Genet 36:452-4, 2005. Pubmed reference: 16167996. DOI: 10.1111/j.1365-2052.2005.01340.x. | |
| 2003 | Cavanagh, J.A.L., Thomson, P.C., Tammen, I., Nicholas, F.W., Raadsma, H.W. : |
| Discriminant analysis of Dexter cattle physical measurement data. Proceedings of the Association for the Advancement of Animal Breeding and Genetics 15:421-424, 2003. | |
| 1999 | Tammen, I., Cavanagh, J.A.L., Cook, R.W., Harper, P.A.W., Raadsma, H.W., Nicholas, F.W. : |
| Combined homozygosity mapping and candidate gene approach for the identification of disease genes in cattle and sheep Archiv fur Tierzucht-Archives of Animal Breeding 42:163-166, 1999. | |
| 1998 | Harper, P.A.W., Latter, M.R., Nicholas, F.W., Cook, R.W., Gill, P.A. : |
| Chondrodysplasia in Australian Dexter cattle Australian Veterinary Journal 76:199-202, 1998. Pubmed reference: 9578757. | |
| 1997 | Usha, A.P., Lester, D.H., Williams, J.L. : |
| Dwarfism in Dexter cattle is not caused by the mutations in FGFR3 responsible for achondroplasia in humans Animal Genetics 28:55-57, 1997. Pubmed reference: 9124710. | |
| 1996 | Reppas, G.P., Rheinberger, R., Canfield, P.J., Watson, G.F. : |
| An unusual congenital cardiac anomaly in a Dexter calf Australian Veterinary Journal 73:115-116, 1996. Pubmed reference: 8660214. | |
| 1990 | Curran, P.L. : |
| Kerry and Dexter Cattle and other ancient Irish breeds Dublin: The Royal Dublin Society , 1990. | |
| 1987 | Kay, V. : |
| Further thoughts on the genetics of Dexter cattle Ark 14:301-304, 1987. | |
| 1986 | Curran, P.L. : |
| The genetics of Dexter cattle The Ark 13:199-202, 1986. | |
| 1978 | Alderson, G.L.H. : |
| A breeding policy for Dexter cattle Ark 5:268-271, 1978. | |
| 1976 | Anon. : |
| Breed of the month - Dexter cattle Great Britain, dwarf and miniature characteristics Ark 3:102-103, 1976. | |
| 1974 | Eldridge, F.E. : |
| A dicentric Robertsonian translocation in a Dexter cow Journal of Heredity 65:353-355, 1974. Pubmed reference: 4141364. | |
| 1960 | Gregory, P.W., Tyler, W.S., Julian, L.M. : |
| Evidence that the Dexter mutant is genetically related to recessive achondroplasia Anatomical Record 138:353-354, 1960. | |
| 1953 | Moyles, G. : |
| Dexter cattle: an historical sketch Journal of the Department of Agriculture, Ireland LVI:109-113, 1953. | |
| Young, G.B. : | |
| Population dynamics of the Dexter breed of cattle. Journal of Agricultural Science 43:369-374, 1953. | |
| 1951 | Young, G.B. : |
| Observations on the frequency and sex ratio of Dexter 'Bulldog' calves Veterinary Record 63:635-636, 1951. | |
| 1946 | Mead, S.W., Gregory, P.W., Regan, W.M. : |
| A recurrent mutation of dominant achondroplasia in cattle. J Hered 37:183-8, 1946. Pubmed reference: 20995083. | |
| 1936 | Punnett, R.C. : |
| The experiments of T.H. Riches concerning the production of monsters in cattle Journal of Genetics 32:65-72, 1936. | |
| 1934 | Taylor, H. : |
| Monstrosities in calves of the Dexter breed and pituitary gland injections Veterinary Record 14:451 only, 1934. | |
| 1929 | Landauer, E. : |
| A possible means of selection for non-deformity breeding in Dexter cattle Veterinary Journal 85:11-15, 1929. | |
| Landauer, W., Thigpen, L.W. : | |
| Studies in chondrodystrophy. IV. Differental blood counts of chondrodystropic chicken embryos and of Dexter cattle Folia Haematoligica 38:1-13, 1929. | |
| 1928 | Downs, W.G. : |
| An American 'Dexter' monster Anatomical Record 37:365-372, 1928. | |
| 1924 | Crew, F.A.E. : |
| The bull-dog calf: a contribution to the study of achondroplasia Royal Society of Medicine, Proceedings 17:39-54, 1924. | |
| 1923 | Crew, F.A.E. : |
| The significance of an achondroplasia-like condition met with in cattle Proceedings of the Royal Society Series B 95:228-256, 1923. | |
| 1909 | Wilson, J. : |
| The origin of the Dexter-Kerry breed of cattle Proceedings of the Royal Dublin Society 12:1-17, 1909. | |
| 1904 | Seligmann, M.B. : |
| Cretinism in calves Journal of Pathology and Bacteriology 9:311-322, 1904. DOI: 10.1002/path.1700090306. | |
| 1893 | Lowne, B.T., Masters, M.T. : |
| Descriptive Catalogue of the Teratological Series in the Museum of the Royal College of Surgeons of England, 2nd edn. London, Royal College of Surgeons. , 1893. DOI: 10.5962/bhl.title.99387. |
Edit History
- Created by Frank Nicholas on 01 Nov 2007
- Changed by Frank Nicholas on 15 Sep 2011
- Changed by Frank Nicholas on 09 Dec 2011
- Changed by Frank Nicholas on 03 Sep 2014
- Changed by Frank Nicholas on 11 Apr 2016
- Changed by Frank Nicholas on 26 Apr 2017
- Changed by Frank Nicholas on 01 May 2017
- Changed by Frank Nicholas on 28 Mar 2019
- Changed by Imke Tammen2 on 19 Jun 2023
- Changed by Imke Tammen2 on 19 Jul 2023