OMIA 002317-9986 : abnormal gait, retinal dysplasia, cataracts, RORB-related in Oryctolagus cuniculus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 601972

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

Species-specific symbol: s^am

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]."

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.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
RORB RAR-related orphan receptor B Oryctolagus cuniculus 1 NC_013669.1 (61058004..61128489) RORB 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.

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
Sauteur d'Alfort sauteur RORB s^am splicing 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

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.
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.
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.

Edit History


  • Created by Imke Tammen2 on 06 Apr 2021
  • Changed by Imke Tammen2 on 06 Apr 2021