OMIA 001271-9913 : Dwarfism, ACAN-related in Bos taurus

In other species: horse

Possibly relevant human trait(s) and/or gene(s) (MIM number): 612813

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive Lethal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2007

Species-specific name: Bulldog calf

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.

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, Jersey, Miniature Highland.

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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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
Dexter Dwarfism, Dexter ACAN BD2 regulatory UMD3.1 21 g.20800319C>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)
Dexter Dwarfism, Dexter ACAN BD1 insertion, small (<=20) UMD3.1 21 g.20844569_20844570insGGCA c.2266_2267insGGCA 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)

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.
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.
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.
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.
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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