Categories: Limbs / fins / digit / tail phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 252150 (trait) , 603707 (gene)

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: 2011

Mapping: Buitkamp et al. (2009) mapped this disorder in Simmental cattle to chromosome BTA23. In stark contrast, Drögemüller et al. (2009) mapped the same disorder in Brown-Swiss cattle to chromosome BTA5 (see OMIA 00059). These results suggest the strong possibility of genetic heterogeneity for this disorder in cattle. (With thanks to Johannes Buitkamp). Interestingly, Seichter et al. (2011) mapped this disorder in Fleckvieh cattle to the same region of BTA23 as in Simmental, suggesting that the Fleckvieh mutation may be the same as the Simmental mutation.

Molecular basis: Building on their 2009 mapping results, Buitkamp et al. (2011) showed that this disorder in Simmental cattle is due to a 2-bp deletion in the MOCS1 gene. This gene encodes two peptides (MOCS1A and MOCS1B) via consecutive open reading frames. These two peptides are involved in the synthesis of molybdenum cofactor (Moco), which is involved in the synthesis of sulphite oxidase, the gene for which (SUOX) is the site of the mutation for the same disorder in Brown Swiss cattle (Drögemüller et al., 2010) (see OMIA 000059-9913). Thus we have an excellent example of mutations in two genes involved in the same biochemical pathway giving rise to the same biochemical deficiency and hence the same clinical signs. This is the first example of this type of genetic heterogeneity to be documented in cattle. As stated by Buitkamp et al. (2011), arachnomelia is thus the first example in cattle of an oligogenic disorder. (With thanks to Johannes Buitkamp) 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) identified the same 2bp deletion in a known carrier. Using a "network-based disease gene prioritization approach", Jiao et al. (2013) independently confirmed the same mutation in Simmental cattle.

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Prevalence: Hu et al. (2022) genotyped "582 bulls and 1-926 cows from Chinese dual-purpose cattle populations of Simmental, Sanhe, Shuxuan, and Xinjiang Brown" for the "MOCS1 mutation c.1224_1225delCA" (OMIA variant 483) and reported that "The frequencies of . . . carriers [of the variant] were 1.08% and 1.65% in the Simmental and Sanhe populations, respectively"; and zero in the other two samples.

Breed: Simmental (Cattle) (VBO_0000380).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: