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) , Growth / size / body region phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 612813 (trait) , 165800 (trait) , 608361 (trait) , 155760 (gene)

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.

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. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

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

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 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 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.

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  • Created by Frank Nicholas on 01 Nov 2007
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