OMIA 001452-9913 : Tail, crooked in Bos taurus

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.

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.

Breed: Belgian Blue.

Associated gene:

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

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
Belgian Blue Tail, crooked MRC2 missense UMD3.1 19 g.47734925T>G c.1906T>G p.C636G 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)
Belgian Blue Tail, crooked MRC2 deletion, small (<=20) UMD3.1 19 g.47740473delAG c.2904-2905delAG p.Gly934X 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)

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.
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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  • Created by Frank Nicholas on 09 Dec 2009
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