OMIA:001451-9913 : Congenital muscular dystonia 2 in Bos taurus (taurine cattle)
Categories: Nervous system phene
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: 2008
Species-specific symbol: CMD2
Species-specific description: In the words of Charlier et al. (2008), "All calves with CMD have episodes of generalized muscle contractures, but careful clinical examination suggested two distinct phenotypes (CMD1 and CMD2)."
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 3.61 Mb region on BTA29 in which 7 affected calves were significantly more homozygous for the same allele at each of many SNPs, when compared with 24 normal controls. An investigation of all 13 genes in that region identified the most likely culprit as being SLC6A5, which encodes a glycine transporter.
Molecular basis: "A missense mutation (T809C) in exon 4, resulting in a L270P substitution in the third membrane-spanning domain of GlyT2" (a glycine transporter). (Charlier et al., 2008). The GlyT2 gene is now called SLC6A5 (and was previously called LOC528050 in NCBI). Gill et al. (2012) reported the same mutation in Belgian Blues from the UK.
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: "CMD2 calves suffer severe episodes of myoclonus upon acoustic or tactile stimulation and typically die within a few hours of birth. CMD2 is reminiscent of congenital myoclonus in Hereford cattle" (Charlier et al., 2008)
Belgian Blue (Cattle) (VBO_0000139).
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|
|SLC6A5||solute carrier family 6 member 5||Bos taurus||29||NC_037356.1 (24373268..24316604)||SLC6A5||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|
|904||Belgian Blue (Cattle)||Congenital muscular dystonia 2||SLC6A5||missense||Naturally occurring variant||ARS-UCD1.2||29||g.24366560A>G||c.809T>C||p.(L270P)||rs3423560860||2008||18344998||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; Breed 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)|
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||Caivio-Nasner, S., López-Herrera, A., González-Herrera, L.G., Rincón, J.C. :|
|Frequency of genotypic markers for genetic disorders, colour, polledness, and major genes in Blanco Orejinegro cattle. Trop Anim Health Prod 53:546, 2021. Pubmed reference: 34779908. DOI: 10.1007/s11250-021-02990-y.|
|2012||Gill, J.L., James, V.M., Carta, E., Harris, D., Topf, M., Scholes, S.F., Hateley, G., Harvey, R.J. :|
|Identification of congenital muscular dystonia 2 associated with an inherited GlyT2 defect in Belgian Blue cattle from the United Kingdom. Anim Genet 43:267-70, 2012. Pubmed reference: 22486497. DOI: 10.1111/j.1365-2052.2011.02255.x.|
|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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