OMIA:000299-9986 : Dwarfism, generic in Oryctolagus cuniculus (rabbit)

In other species: white-tufted-ear marmoset , dog , domestic cat , Asiatic elephant , horse , pig , red deer , Northern giraffe , taurine cattle , indicine cattle (zebu) , goat , sheep , callipterus cichlid , Angolan giraffe

Categories: Skeleton phene (incl. short stature & teeth) , Growth / size / body region phene

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal incomplete dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2017

Species-specific symbol: dw

Species-specific description: Robinson (1958, pp. 343-346) provides an extensive summary of this form of proportionate dwarfism. The effect of the mutant dw allele on a wide range of traits was reported by Crary and Sawin (1949), Sawin and Dietz (1950), Sawin and Curran (1952), and in three 1955 papers by Latimer and Sawin. The results of Carneiro et al. (2017) "imply that small size in dwarf rabbits results from a large effect, loss-of-function (LOF) mutation in HMGA2 combined with polygenic selection."

History: A single-locus proportionate dwarfism that is autosomal recessive lethal was first reported by Greene et al. (1934) and subsequently by Kroning (1939). As summarised by Robinson (1958), "The growth rate of heterozygotes is comparable to that of normals but the size difference [approximately two-thirds of normal homozygotes] at birth persists into adult life. They are normal in other respects but for a greater tendency for the females to accumulate fat unless bred from regularly."

Inheritance: As reported by Carneiro et al. (2017), "The dwarf phenotype characterizes the smallest of rabbit breeds and is governed largely by the effects of a single dwarfing allele with an incompletely dominant effect on growth. Dwarf rabbits typically weigh under 1 kg and have altered craniofacial morphology. The dwarf allele is recessive lethal and dwarf homozygotes die within a few days of birth. The dwarf phenotype is expressed in heterozygous individuals and rabbits from dwarf breeds homozygous for the wild-type allele are normal, although smaller when compared to other breeds." The mode of inheritance has been changed from 'autosomal recessive lethal' to 'autosomal incompletely dominant' in May 2022 to reflect that animals with a single copy of the HMGA2 mutation present with a milder form of dwarfism.

Mapping: Castle and Sawin (1941) showed that the dw gene is linked to agouti (OMIA 000201-9986) in linkage group IV.

Molecular basis: Carneiro et al. (2017) showed "that the dwarf allele constitutes a ~12.1 kb deletion overlapping the promoter region and first three exons of the HMGA2 gene leading to inactivation of this gene." Very interestingly, mutation in this same gene is associated with body-size variation in dogs (OMIA 001968-9615) and horses (OMIA 001968-9796), and with beak size in Darwin's finches (OMIA 001992-48881); see the hyperlink to HMGA2 under the heading "OMIA gene details page" in the table below.

Clinical features: As reported by Green et al. (1934): "The [homozygous] dwarfs of this stock are born alive and occasionally they are capable of nursing, but so far, none of them has lived longer than a few days. They are delicately formed and to outward appearance are fully developed except for the bones of the calvarium, which, as a rule, are incompletely calcified."

Pathology: The pathology in individuals homozygous for the dwarf mutation leads to death. Although heterozygous individuals are viable and can live a healthy life, due to their craniofacial morphology they are particularly prone to dental disorders due to their proportionately smaller heads and longer jaw, which can cause issues with misalignment. This mandibular prognathism predisposes to abnormal dental wear, causing altered teeth positions or elongation due to abnormal grinding patterns (Mäkitaipale, Harcourt-Brown and Laitinen-Vapaavuori, 2015). [IT thanks DVM student Carmen Ip for contributions to this entry in April 2022].

Control: Breeding of two animals that are both heterozgyous for the dwarf mutation should be avoided. For the breeding of dwarf rabbits, each breeding pair should include an animal heterozygous for the dwarf mutation (dwarf rabbit) and an animal that does not have the dwarf mutation. This will avoid the birth of non viable homozygous dwarfs and result in the birth of 50% viable (heterozygous) dwarfs and 50% normal sized rabbits.

Breeds: Dwarf, long-haired, Holland Lop (Rabbit) (VBO_0001258), Netherland dwarf (Rabbit) (VBO_0001266).
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
HMGA2 high mobility group AT-hook 2 Oryctolagus cuniculus 4 NC_067377.1 (52276651..52407628) HMGA2 Homologene, Ensembl , NCBI gene


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
689 Dwarf, long-haired Holland Lop (Rabbit) Netherland dwarf (Rabbit) Dwarfism HMGA2 dw deletion, gross (>20) Naturally occurring variant 4 "that the dwarf allele constitutes a ~12.1 kb deletion overlapping the promoter region and first three exons of the HMGA2 gene leading to inactivation of this gene." 2017 27986804

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:000299-9986: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.

2021 Derks, M.F.L., Steensma, M. :
Review: Balancing selection for deleterious alleles in livestock. Front Genet 12:761728, 2021. Pubmed reference: 34925454. DOI: 10.3389/fgene.2021.761728.
2017 Carneiro, M., Hu, D., Archer, J., Feng, C., Afonso, S., Chen, C., Blanco-Aguiar, J.A., Garreau, H., Boucher, S., Ferreira, P.G., Ferrand, N., Rubin, C.J., Andersson, L. :
Dwarfism and altered craniofacial development in rabbits is caused by a 12.1 kb deletion at the HMGA2 locus. Genetics 205:955-965, 2017. Pubmed reference: 27986804. DOI: 10.1534/genetics.116.196667.
2015 Mäkitaipale, J., Harcourt-Brown, F.M., Laitinen-Vapaavuori, O. :
Health survey of 167 pet rabbits (Oryctolagus cuniculus) in Finland. Vet Rec 177:418, 2015. Pubmed reference: 26475828. DOI: 10.1136/vr.103213.
1997 Wegner, W. :
Problematic aspects of breeding dwarf rabbits [German] Deutsche Tierarztliche Wochenschrift 104:181-183, 1997. Pubmed reference: 9289403.
1990 Komatsu, M., Imaoka, K., Satoh, M., Mikami, H. :
Hereditary C8-alpha-gamma deficiency associated with dwarfism in the rabbit. Journal of Heredity 81:413-417, 1990.
1981 Webber, R.J., Fox, R.R., Sokoloff, L. :
In vitro culture of rabbit growth plate chondrocytes. 2. Chondrodystrophic mutants. Growth 45:269-78, 1981. Pubmed reference: 6458543.
1958 Robinson, R. :
Genetic studies of the rabbit. Bibliographia Genetica 17:229–558, 1958.
1957 Latimer, H.B., Sawin, P.B. :
Morphogenetic studies of the rabbit. XV. Measurements of the digestive tube and of its parts in normal and dwarf rabbits of race X. Anat Rec 129:1-16, 1957. Pubmed reference: 13509179.
1955 Latimer, H.B., Sawin, P.B. :
Morphogenetic studies of the rabbit. XIII. The influence of the dwarf gene upon organ size and variability in race X. Anat Rec 123:447-66, 1955. Pubmed reference: 13292775.
Latimer, H.B., Sawin, P.B. :
The weight of the brain, of its parts and the weight and length of the spinal cord in the rabbit (race X). J Comp Neurol 103:513-39, 1955. Pubmed reference: 13286369. DOI: 10.1002/cne.901030307.
Latimer, H.B., Sawin, P.B. :
Morphogenetic studies of the rabbit. XII. Organ size in relation to body weights in adults of small sized race X. Anat Rec 123:81-102, 1955. Pubmed reference: 13268896. DOI: 10.1002/ar.1091230106.
1952 Sawin, P.B., Curran, R.H. :
Genetic and physiological background of reproduction in the rabbit. 1. The problem and its biological significance. Journal of Experimental Zoology 128:165-201, 1952.
1950 Sawin, P.B., Dietz, D.B. :
Morphogenetic studies of the rabbit. IX. Masking of prenatal growth gradients in adults. Moderne Biologie (eds Griineberg, H. and Ulrich, W.) :215-229, 1950.
1949 Crary, D.D., Sawin, P.B. :
Morphogenetic studies in the rabbit. VI. Genetic factors influencing the ossification pattern of the limbs. Genetics 34:508-23, 1949. Pubmed reference: 17247330. DOI: 10.1093/genetics/34.5.508.
1941 Castle, W.E., Sawin, P.B. :
Genetic linkage in the rabbit. Proc Natl Acad Sci U S A 27:519-23, 1941. Pubmed reference: 16588495. DOI: 10.1073/pnas.27.11.519.
1940 Greene, H.S. :
A dwarf mutation in the rabbit: the constitutional influence on homozygous and heterozygous individuals J Exp Med 71:839-56, 1940. Pubmed reference: 19871001.
1939 Kroning, F. :
Ein neuer Fall erblichen Zwergwuchs beim Kaninchen Biologisches Zentralblatt 59:268-272, 1939.
1937 Nachtsheim, H. :
Erbpathologische Untersuchungen am Kaninchen [Investigation of inherited defects in rabbits] Z. indo Abst. u. Vererbgs 73:463-466, 1937. DOI: 10.1007/BF01847500.
1934 Greene, H.S., Hu, C.K., Brown, W.H. :
A lethal dwarf mutation in the rabbit with stigmata of endocrine abnormality Science 79:487-8, 1934. Pubmed reference: 17840734. DOI: 10.1126/science.79.2056.487.

Edit History

  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 05 Oct 2011
  • Changed by Frank Nicholas on 28 Apr 2016
  • Changed by Frank Nicholas on 03 May 2016
  • Changed by Frank Nicholas on 30 Dec 2016
  • Changed by Frank Nicholas on 09 May 2017
  • Changed by Imke Tammen2 on 18 Jan 2022
  • Changed by Imke Tammen2 on 23 May 2022
  • Changed by Imke Tammen2 on 24 May 2022
  • Changed by Imke Tammen2 on 06 Mar 2023