OMIA 001003-9913 : Thrombopathia in Bos taurus

In other species: dog , pig

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 185050 , 603962 , 615888 , 605577

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2007

Cross-species summary: A disorder of blood coagulation resulting from a failure of ADP release from platelets on stimulation by aggregating factors such as thromboplastin. In a thorough review, Boudreaux (2008) suggests that this disorder "should probably be referred to as CalDAG-GEFI thrombopathias or CalDAG-GEFI platelet disorders because the specific cause of the disorders is now known".

Species-specific name: Simmental hereditary thrombopathy

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.

Associated gene:

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

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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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
Fleckvieh Simmental Thrombopathia RASGRP2 missense UMD3.1 29 g.43599204T>C c.701T>C p.L234P 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)

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.
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 Thrombosis & Haemostasis 76:1047-1052, 1996. Pubmed reference: 8972030.
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., 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., 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.

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  • Created by Frank Nicholas on 03 Nov 2010
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