OMIA:002433-9913 : Thrombopathia, RASGRP2-related in Bos taurus
In other species: dog
Categories: Haematopoietic system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 615888 (trait) , 605577 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2007
Species-specific name: Simmental hereditary thrombopathy; bleeding disorder;
History: Simmental hereditary thrombopathy was previously listed as OMIA 001003-9913 : Thrombopathia in Bos taurus
Mapping: In a GWAS involving 6 affected and 43 normal Fleckvieh (each genotyped with the Illumina BovineHD SNP Chip, yielding 652,856 informative SNPs), Jansen et al. (2013) mapped this disorder in Fleckvieh to chromosome BTA29. Subsequent autozygosity mapping narrowed the region to a 6.3Mb interval that contains the RASGRP2 gene.
Molecular basis: On the strength of a clear candidate gene in which mutations cause the same disorder in dogs (OMIA 001003-9615), Boudreaux et al. (2007) reported that this disorder in a Simmental calf is due to a missense mutation (c.701T>C) in the CalDAG-GEFI gene which is now called RASGRP2.
Jansen et al. (2013) reported that "Sanger sequencing confirmed that all thrombopathic animals are homozygous for the [same] pertinent amino acid exchange (c.701T > C, p.L234P, Chr29:43599204" (UMD3.1 reference coordinates).
Aebi et al. (2016) reported the same causal mutation in affected Simmental cattle in Switzerland.
Prevalence: In a project involving the whole-genome sequencing (WGS) of 43 Fleckvieh cattle with average coverage 7.46X (range 4.17X to 24.98X), Jansen et al. (2013) reported that 8/43 carried the c.701T>C mutation, giving a gene frequency of 9% in this breed.
Aebi et al. (2016) reported "A frequency of 10% carriers for the associated mutation was detected in a sample of 145 Simmental sires which were used 2013 for artificial insemination in Switzerland."
Breeds: Fleckvieh-Simmental, Germany (Cattle) (VBO_0002354), Simmental (Cattle) (VBO_0000380).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|RASGRP2||RAS guanyl releasing protein 2||Bos taurus||29||NC_037356.1 (42984113..42969393)||RASGRP2||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|
|209||Simmental (Cattle)||Thrombopathia||RASGRP2||missense||Naturally occurring variant||ARS-UCD1.2||29||g.42978791A>G||c.701T>C||p.(L234P)||rs385444696||rs385444696||2007||18039909||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)|
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.
|2016||Aebi, M., Wiedemar, N., Drögemüller, C., Zanolari, R. :|
|[Inherited thrombopathia in Simmental cattle]. Schweiz Arch Tierheilkd 158:102-8, 2016. Pubmed reference: 27145685 .|
|2015||Zerbin, I., Metzger, J., Dierks, C., Distl, O. :|
|Segregation of the hereditary thrombopathia-associated polymorphism in polled German Fleckvieh cattle. Anim Genet 46:584-5, 2015. Pubmed reference: 26154292 . DOI: 10.1111/age.12322.|
|2013||Jansen, S., Aigner, B., Pausch, H., Wysocki, M., Eck, S., Benet-Pagès, A., Graf, E., Wieland, T., Strom, T.M., Meitinger, T., Fries, R. :|
|Assessment of the genomic variation in a cattle population by re-sequencing of key animals at low to medium coverage. BMC Genomics 14:446, 2013. Pubmed reference: 23826801 . DOI: 10.1186/1471-2164-14-446.|
|2008||Boudreaux, MK. :|
|Characteristics, diagnosis, and treatment of inherited platelet disorders in mammals. J Am Vet Med Assoc 233:1251-9, 1190, 2008. Pubmed reference: 18922051 . DOI: 10.2460/javma.233.8.1251.|
|2007||Boudreaux, MK., Schmutz, SM., French, PS. :|
|Calcium diacylglycerol guanine nucleotide exchange factor I (CalDAG-GEFI) gene mutations in a thrombopathic Simmental calf. Vet Pathol 44:932-5, 2007. Pubmed reference: 18039909 . DOI: 10.1354/vp.44-6-932.|
|2000||Mapletoft, R.J., Schmutz, S.M., Searcy, G.P. :|
|A study of the inheritance of a bleeding disorder in Simmental cattle Canadian Veterinary Journal - Revue Veterinaire Canadienne 41:791-793, 2000.|
|1997||Gentry, P.A., Cheryk, L.A., Shanks, R.D., Healey, R. :|
|An inherited platelet function defect in a Simmental crossbred herd Canadian Journal of Veterinary Research - Revue Canadienne de Recherche Veterinaire 61:128-133, 1997. Pubmed reference: 9114964 .|
|1996||Frojmovic, M.M., Wong, T., Searcy, G.P. :|
|Platelets from bleeding Simmental cattle have a long delay in both ADP-activated expression of GpIIB-IIIA receptors and fibrinogen-dependent platelet aggregation. Thromb Haemost. 76:1047-1052, 1996. Pubmed reference: 8972030 .|
|1995||Navarre, C.B., Kasari, T.R., Green, R.A. :|
|Platelet function defect in a 5-day-old Simmental calf. J Vet Intern Med 9:283-5, 1995. Pubmed reference: 8523328 . DOI: 10.1111/j.1939-1676.1995.tb01082.x.|
|1994||Searcy, G.P., Frojmovic, M.M., Mcnicol, A., Robertson, C., Wong, T., Gerrard, J.M. :|
|Platelets from bleeding Simmental cattle mobilize calcium, phosphorylate myosin light chain and bind normal numbers of fibrinogen molecules but have abnormal cytoskeletal assembly and aggregation in response to ADP. Thrombosis and Haemostasis 71:240-246, 1994. Pubmed reference: 8191406 .|
|1993||Steficek, B.A., Thomas, J.S., Baker, J.C., Bell, T.G. :|
|Hemorrhagic Diathesis Associated with a Hereditary Platelet Disorder in Simmental Cattle Journal of Veterinary Diagnostic Investigation 5:202-207, 1993. Pubmed reference: 8507698 .|
|Steficek, B.A., Thomas, J.S., Mcconnell, M.F., Bell, T.G. :|
|A primary platelet disorder of consanguineous Simmental cattle. Thrombosis Research 72:145-153, 1993. Pubmed reference: 8303652 .|
|1990||Searcy, G.P., Petrie, L. :|
|Clinical and laboratory findings of a bleeding disorder in 8 Simmental cattle. Canadian Veterinary Journal-Revue Veterinaire Canadienne 31:101-103, 1990.|
|Searcy, G.P., Sheridan, D., Dobson, K.A. :|
|Preliminary studies of a platelet function disorder in Simmental cattle. Canadian Journal of Veterinary Research-Revue Canadienne de Recherche Veterinaire 54:394-396, 1990. Pubmed reference: 2379119 .|
- Created by Imke Tammen2 on 25 Sep 2021
- Changed by Imke Tammen2 on 25 Sep 2021