OMIA 002317-9986 : Abnormal gait, retinal dysplasia, cataracts, RORB-related in Oryctolagus cuniculus
Category: Behaviour / neurological phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 601972 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2021
Species-specific name: disrupted saltatorial locomotion, sauteur phenotype, acrobat
Species-specific symbol: s^am; ak
Species-specific description: Carneiro et al. (2021): "Saltatorial locomotion is a type of hopping gait that in mammals can be found in rabbits, hares, kangaroos, and some species of rodents. ... Here, we take advantage of one strain of domesticated rabbits, the sauteur d’Alfort, that exhibits an abnormal locomotion behavior defined by the loss of the typical jumping that characterizes wild-type rabbits. Strikingly, individuals from this strain frequently adopt a bipedal gait using their front legs. ... Additional anatomical problems have also been described in sauteur rabbits, they are born blind because of retinal dysplasia and start developing cataracts after their first year of life [Theret, 1961; Boucher et al., 1996]."
History: Robinson (1958, p. 330): "A very curious form of nervous behaviour has been reported by LETARD (1935, 1943) affecting the gait. ... LETARD states that the condition is inherited as a Mendelian recessive and is presumably due to a single gene ak. Some eye defects (cataract, displacement of the lens) appear to be associated with the anomalous gait; or at least they appear to be inseparable from it. ... . A strikingly similar form of behaviour has been observed in a stud of Dutch rabbits in England. The exact mode of inheritance is unknown ... (ROBINSON, unpublished observations).
Carneiro et al. (2021) identified a likely causal variant.
Inheritance: Carneiro et al. (2021): "The sauteur phenotype, including abnormal gait and ocular lesions, has a simple genetic basis controlled by a single autosomal recessive allele (s^am) [Letard, 1935; Boucher et al., 1996]."
Mapping: Carneiro et al. (2021) employed a bulked segregant analysis to map the causal locus for the sauteur phenotype to a 5.4 Mb region on chromosome 1.
Molecular basis: Using the whole-genome sequencing data generated for the bulked segregant analysis, Carneiro et al. (2021) searched the 5.4 Mb candidate region for potential causal variants and identified a splice site mutation in RORB as likely causal variant. "This variant corresponds to a change from GT to AT in the 5’ donor site of intron 9 (chr1: 61,103,503bp)" (Carneiro et al., 2021). RORB cDNA analysis identified a high proportion of aberrant RORB transcripts in sauteur rabbits (Carneiro et al., 2021).
Pathology: Carneiro et al., 2021: "immunohistochemistry (IHC) was performed on the spinal cord of newborn rabbits from our experimental cross. ... In rabbits homozygous for the wild-type allele, RORB is localized in the nucleus of a population of dorsal horn neurons. ... In the spinal cord from rabbits heterozygous for the sauteur allele (+/s^am), the number of neurons expressing RORB was approximately 25% lower than in the wild-type animals ... . In contrast, in rabbits homozygous for the sauteur allele (s^am/ s^am), the expression of RORB was undetectable by IHC."
Breed: Sauteur d'Alfort.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|RORB||RAR-related orphan receptor B||Oryctolagus cuniculus||1||NC_067374.1 (74952820..75174784)||RORB||Homologene, Ensembl, NCBI gene|
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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|
|1297||Sauteur d'Alfort||Sauteur||RORB||s^am||splicing||Naturally occurring variant||OryCun2.0||1||g.61103503G>A||This variant corresponds to a change from GT to AT in the 5’ donor site of intron 9 (Carneiro et al., 2021)||2021||33764968|
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||Carneiro, M., Vieillard, J., Andrade, P., Boucher, S., Afonso, S., Blanco-Aguiar, J.A., Santos, N., Branco, J., Esteves, P.J., Ferrand, N., Kullander, K., Andersson, L. :|
|A loss-of-function mutation in RORB disrupts saltatorial locomotion in rabbits. PLoS Genet 17:e1009429, 2021. Pubmed reference: 33764968. DOI: 10.1371/journal.pgen.1009429.|
|2002||Audigier, I., Renous, S. :|
|Les allures du lapin normal peuvent-elles expliquer la marche acrobatique du «lapin sauteur d’Alfort»? Mammalia 66:563–578, 2002.|
|1996||Boucher, S., Renard, J.P., Joly, T. :|
|The “Alfort jumper” rabbit: historic, description and characterization. Proc 6th World Rabbit Congr. 2:255-258, 1996.|
|1991||Boucher, S. :|
|Le lapin Sauteur d’Alfort Rev Avic 3:91-95, 1991.|
|1961||Theret, M. :|
|Aspects génétiques de quelques anomalies oculaires chez les animaux domestiques. [Genetic aspect of some ocular anomalies in domestic animals]. Bull Mem Soc Fr Ophtalmol 74:505-14, 1961. Pubmed reference: 13980887.|
|1958||Robinson, R. :|
|Genetic studies of the rabbit. Bibliographia Genetica 17:229–558, 1958.|
|1943||Letard, E. :|
|Troubles de la locomotion et troubles de la vision chez le lapin, liaison héréditaire. Bull Acad Vet Fr 16:184-192, 1943.|
|1935||Letard, E. :|
|Une mutation nouvelle chez le lapin. Bull Acad Vet Fr 8:608-610, 1935.|
- Changed by Imke Tammen2 on 06 Apr 2021
- Created by Imke Tammen2 on 06 Apr 2021
- Changed by Imke Tammen2 on 31 Oct 2022