OMIA 002297-9913 : Tetradysmelia in Bos taurus

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 618021 (trait) , 610575 (gene) , 618022 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2020

Cross-species summary: Tetradysmelia refers to the severe reduction of all limb parts distal of the scapula and the pelvic girdle. This phene may be similar to 'limbless' in chicken (OMIA 000602-9031).

History: In the 1990s, a Holstein Friesian bull was mated to five of his daughters using an embryo transfer program to produce a backcross family. Off 24 offspring, 6 stillborn calves lacked all four limbs (Kühn et al., 1998; Becker et al., 2020). Analysis of candidate genes EN1 and FGF10 did not identify likely causative variants (Kühn et al., 1999 & 2002).

Mapping: Applying a homozygosity mapping approach, Becker et al. (2020) identified a shared region of homozygosity of 10.54 Mb on chromosome 14 ranging from 52.42 to 62.96 Mb in the three genotyped affected animals that was not present in the dams and unaffected siblings.

Molecular basis: Becker et al. (2020) "detected a 50-kb deletion in the targeted chromosomal region that was in the heterozygous state in the cases’ sire" in whole genome sequencing data and "confirmed that this detected deletion segregated perfectly within the family with tetradysmelia. The deletion spanned three exons of the bovine R-spondin 2 (RSPO2) gene, which encode three domains of the respective protein."

Clinical features: Affected calves were aborted or stillborn and presented with severe limb malformations of all limbs: distal parts of the fore and hindlimbs were completely missing in most affected animals, while one affected animal had partly developed limbs. One affected animal "lacked the symphyseal fusion of the rostral ends of the mandibulae and" and one animal "showed a mild brachygnathia superior." (Becker et al., 2020).

Prevalence: Only six affected calves have been reported (Becker et al., 2020).

Breed: Holstein Friesian.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
RSPO2 R-spondin 2 Bos taurus 14 NC_037341.1 (56384062..56556667) RSPO2 Homologene, Ensembl, NCBI gene

Variants

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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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
Holstein Friesian Tetradysmelia RSPO2 delins, gross (>20) ARS-UCD1.2 14 g.56451029_56501201delinsTGACAA a 50-kb deletion spanning three exons of the R-spondin 2 (RSPO2) gene 2020 33176673

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.
2020 Becker, D., Weikard, R., Schulze, C., Wohlsein, P., Kühn, C. :
A 50-kb deletion disrupting the RSPO2 gene is associated with tetradysmelia in Holstein Friesian cattle. Genet Sel Evol 52:68, 2020. Pubmed reference: 33176673. DOI: 10.1186/s12711-020-00586-y.
2005 Kühn, C., Weikard, R., Laurent, P., Goldammer, T. :
Assignment of the fibroblast growth factor 10 (FGF10) gene to bovine chromosome 20q16-->q17 by fluorescence in situ hybridization and somatic cell panel analysis. Cytogenet Genome Res 109:533, 2005. Pubmed reference: 15906471.
2002 Kühn, C., Weikard, R., Panicke, L., Schwerin, M. :
Fibroblast growth factor 10: a potential candidate gene for bovine developmental defect Tetradysmelia? Proceedings of the 7th World Congress on Genetics Applied to Livestock Production, Montpellier, France :, 2002.
1999 Kühn, C., Weikard, R., Panicke, L., Schwerin, M. :
Genetic variation within the EN1 gene is not responsible for inherited defect "Tetradysmelia" in cattle. Schriftenreihe / FBN, Forschungsinstitut für die Biologie landwirtschaftlicher Nutztiere: International Symposium on Candidate Genes for Animal Health; 25–27 August 1999; Rostock 12:64, 1999.
1998 Kühn, C., Weikard, R., Panicke, L., Schwerin, M. :
Genetic investigation of the defect 'Tetra-dysmelia' in Holstein cattle by application of genetic markers. Animal Genetics Supplement 29:35, 1998.

Edit History


  • Created by Imke Tammen2 on 23 Nov 2020
  • Changed by Imke Tammen2 on 23 Nov 2020
  • Changed by Imke Tammen2 on 26 Nov 2020