OMIA 000299-9986 : Dwarfism in Oryctolagus cuniculus

See the equivalent entry at NCBI

In other species: domestic cat , cattle , dog , goat , pig , sheep , horse

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive Lethal

Considered a defect: yes

Key mutation known: yes

Year key mutation 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." Examination of selective sweeps by the same authors.

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."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
HMGA2 high mobility group AT-hook 2 Oryctolagus cuniculus 4 NC_013672.1 (44716480..44850380) HMGA2 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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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
Dwarfism HMGA2 deletion, gross (>20) "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

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 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.
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.
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.
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.
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.
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.

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