OMIA:001452-9913 : Tail, crooked in Bos taurus (taurine cattle)
Categories: Limbs / fins / digit / tail phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 612264 (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: 2009
Species-specific name: Crooked tail syndrome
Species-specific symbol: CTS
Species-specific description: "Affected animals have a crooked tail and shortened head, growth retardation, extreme muscularity and spastic paresia, although some characteristics show variable penetrance. CTS is not lethal per se, but causes substantial economic losses due to growth retardation and treatment." (Charlier et al., 2008)
Mapping: In a pioneering use of tens of thousands of SNP markers ("using either the 25K Affymetrix SNP panel or a custom-made 60K Illumina panel"), Charlier et al. (2008) identified a single 2.42 Mb region on BTA19 in which 8 affected calves were significantly more homozygous for the same allele at each of many SNPs, when compared with 14 normal controls.
Molecular basis: Following hot on the heels of the mapping of this disorder, Fasquelle et al. (2009) showed it to be due to a frameshifting 2-bp deletion (c.2904-2905delAG) in the MRC2 gene (encoding mannose receptor C type 2).
Following the publication of the 2009 paper, 18 new cases with exactly the same clinical signs were detected, and were all shown by Sartelet et al. (2012) to be NOT homozygous for this (recessive) mutation, but instead to be heterozygous for this mutation. How could this be? Why would heterozygotes for a recessive disorder show all the clinical signs usually seen in homozygotes? Detailed investigation by Sartelet et al. (2012) of these 18 cases showed each of them to be a compound heterozygote for the c.2904-2905delAG mutation and a newly identified mutation, namely c.1906T>C, in the same gene. The former mutation results in no functional peptide, and the latter mutation results in illegitimate oligomerization of the peptide. Consequently, compound heterozygotes for these two mutations have no fully functional gene product, and hence are affected with the disorder.
Have human generated variants been created, e.g. through genetic engineering and gene editing
Genetic testing: The detection of a second mutation by Sartelet et al. (2012) in the same (MRC2) gene in the same breed of cattle (described in the Molecular basis section above) provides a cautionary tale for the provision of genetic testing for disorders: clients must always be warned that available tests may not detect all relevant mutations. In other words, there is always the chance that the same or similar clinical signs can result from a mutation that has not yet been detected.
Belgian Blue (Cattle) (VBO_0000139),
Brown Swiss (Cattle) (VBO_0000166).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|MRC2||mannose receptor, C type 2||Bos taurus||19||NC_037346.1 (47043142..47103169)||MRC2||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|
|208||Belgian Blue (Cattle)||Tail, crooked||MRC2||missense||Naturally occurring variant||ARS-UCD1.2||19||g.47089627T>G||c.1906T>G||p.(C636G)||rs466131011||rs466131011||2012||22497452||Breed and some variant information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)|
|491||Belgian Blue (Cattle)||Tail, crooked||MRC2||deletion, small (<=20)||Naturally occurring variant||ARS-UCD1.2||19||g.47095176_47095177del||c.2904_2905del||p.(G934*)||2009||19779552||Breed and some variant information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170) 210908 the entry g.47740473delAG can't be correct because if two bases have been deleted, the g. notation must include the two relevant base positions. FN BLASTED the sequence CCAGACCTGCCGCCCACAG obtained from Fig 3 against UMD3.1.1, and determined that the entry should be g.47740474_47740475del|
Cite this entry
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.|
|2019||Zepeda-Batista, J.L., Parra-Bracamonte, G.M., Núñez-Domínguez, R., Ramírez-Valverde, R., Ruíz-Flores, A., Zepeda-Batista, J.L., Parra-Bracamonte, G.M., Núñez-Domínguez, R., Ramírez-Valverde, R., Ruíz-Flores, A. :|
|Screening genetic diseases prevalence in Braunvieh cattle. Trop Anim Health Prod 51:25-31, 2019. Pubmed reference: 30014197. DOI: 10.1007/s11250-018-1655-y.|
|2014||Druet, T., Ahariz, N., Cambisano, N., Tamma, N., Michaux, C., Coppieters, W., Charlier, C., Georges, M. :|
|Selection in action: dissecting the molecular underpinnings of the increasing muscle mass of Belgian blue cattle. BMC Genomics 15:796, 2014. Pubmed reference: 25228463. DOI: 10.1186/1471-2164-15-796.|
|2012||Sartelet, A., Klingbeil, P., Franklin, C.K., Fasquelle, C., Géron, S., Isacke, C.M., Georges, M., Charlier, C. :|
|Allelic heterogeneity of Crooked Tail Syndrome: result of balancing selection? Anim Genet 43:604-7, 2012. Pubmed reference: 22497452. DOI: 10.1111/j.1365-2052.2011.02311.x.|
|2009||Fasquelle, C., Sartelet, A., Li, W., Dive, M., Tamma, N., Michaux, C., Druet, T., Huijbers, IJ., Isacke, CM., Coppieters, W., Georges, M., Charlier, C. :|
|Balancing selection of a frame-shift mutation in the MRC2 gene accounts for the outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle. PLoS Genet 5:e1000666, 2009. Pubmed reference: 19779552. DOI: 10.1371/journal.pgen.1000666.|
|2008||Charlier, C., Coppieters, W., Rollin, F., Desmecht, D., Agerholm, JS., Cambisano, N., Carta, E., Dardano, S., Dive, M., Fasquelle, C., Frennet, JC., Hanset, R., Hubin, X., Jorgensen, C., Karim, L., Kent, M., Harvey, K., Pearce, BR., Simon, P., Tama, N., Nie, H., Vandeputte, S., Lien, S., Longeri, M., Fredholm, M., Harvey, RJ., Georges, M. :|
|Highly effective SNP-based association mapping and management of recessive defects in livestock. Nat Genet 40:449-54, 2008. Pubmed reference: 18344998. DOI: 10.1038/ng.96.|
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