In other species: dog

Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 615888 (trait) , 605577 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0014386: platelet-type bleeding disorder 18

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: 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).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: