Categories: Skeleton phene (incl. short stature & teeth)

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 606887 (gene) , 272300 (trait)

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: 2010

History: The paper by Drögemüller et al. (2010) appears to be the first publication to report the use of sequence-capture of a candidate region followed by resequencing to identify the molecular basis of a disorder in domestic animals.

Mapping: Drögemüller et al. (2009) mapped this disorder in Brown Swiss cattle to a 7 Mb region on chromosome BTA5. In stark contrast, Buitkamp et al. (2009) demonstrated that a locus for a similar defect in Simmental cattle maps to BTA23 (see OMIA 001541). (With thanks to Tosso Leeb). These results suggested the strong possibility of genetic heterogeneity for this disorder in cattle. In the course of their large-scale study of BovineSNP50 BeadChip haplotypes that are common but never homozygous, VanRaden et al. (2011) confirmed the mapping of this disorder to BTA5, at 62 Mb, in Brown Swiss cattle (UMD 3.0 genome assembly).

Molecular basis: Having a good idea of the map location of the gene responsible for this disorder in Brown Swiss cattle, Drögemüller et al. (2010) used sequence capture followed by resequencing to identify a single base insertion in the gene for sulfite oxidase (SUOX) as being causative for this disorder in this breed. The synthesis of sulfite oxidase is dependent upon molybdenum cofactor (Moco), whose synthesis is dependent upon two peptides (MOCS1A and MOCS1B) that are encoded (via consecutive reading frames) by the gene MOCS1. Consistent with their mapping results, Buitkamp et al. (2011) have shown that arachnomelia in Simmental cattle is due to a 2-bp deletion in the MOCS1 gene (see OMIA 001541). 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.

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

Clinical features: Drögemüller et al. (2010) summarized the clinical features: "Arachnomelia is a genetic disease in cattle characterized by skeletal abnormalities. Affected calves are usually stillborn with a spidery appearance and an abnormally shaped skull. The bones of the limbs are prolonged (dolichostenomelia) with marked thinning of the diaphyses that fracture easily in the course of forced birth assistance. Additional dysmorphic features are variable, e.g. defects of the vertebral column and sometimes cardiac malformations."

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 "c.363_364insG mutation in the SUOX gene" (OMIA variant 587) and reported that this variant was absent from all four samples.

Breed: Brown Swiss (Cattle) (VBO_0000166).
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: