OMIA 001450-9913 : Congenital muscular dystonia 1 in Bos taurus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 601003

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: CMD1

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 2.12 Mb region on BTA25 in which 12 affected calves were significantly more homozygous for the same allele at each of many SNPs, when compared with 14 normal controls. An investigation of comparative candidate genes in this region identified six possible candidate genes. Sequencing revealed the causative molecular lesion in the ATPA2A1 gene, whose peptide is involved in calcium flow into the sarcoplasmic reticulum.

Molecular basis: "A missense mutation (C1676T) leading to a R559C substitution in exon 14 of ATP2A1" (Charlier et al., 2008)

Clinical features: "Calves affected by CMD1 show impaired swallowing, fatigue upon stimulation or exercise, and muscle myotonia resulting in an inability to flex limbs and injurious falling. CMD1 calves usually die within a few weeks as a result of respiratory complications." (Charlier et al. (2008)

Breed: Belgian Blue.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ATP2A1 ATPase, Ca++ transporting, cardiac muscle, fast twitch 1 Bos taurus 25 NC_037352.1 (25946618..25929251) ATP2A1 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 required column headers

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 Red and White Dutch Congenital muscular dystonia 1 ATP2A1 missense UMD3.1 25 g.26191380C>T c.1675C>T p.R559C 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)

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.
2018 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 :, 2018. Pubmed reference: 30014197. DOI: 10.1007/s11250-018-1655-y.
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.

Edit History


  • Created by Frank Nicholas on 30 Mar 2008
  • Changed by Frank Nicholas on 07 Oct 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 21 May 2013
  • Changed by Frank Nicholas on 16 Aug 2013