Phenotype Details
Phene ID
32
Name
Citrullinaemia
Phene Name
N/A
OMIA ID
194
Species ID
9913
Characterised
Yes
Characterised Year
1989
Linked Genes
SymbolGene IDChromosomeDescription
ASS128072611argininosuccinate synthase 1
Linked Variants
Variant IDPhenotypeGene IDDeleteriousChromosomeGenomicTranscriptProtein
289Citrullinaemia280726111NC_037338.1:g.100781668C>TNM_173892.4:c.256C>TNP_776317.1:p.(R86*)
Linked Breeds
BreedBreed IDSpecies IDVBO Term
Blanco Orejinegro, Colombia (Cattle)13409913http://purl.obolibrary.org/obo/VBO_0004602
Brown Swiss (Cattle)599913http://purl.obolibrary.org/obo/VBO_0000166
Holstein Friesian (Cattle)739913http://purl.obolibrary.org/obo/VBO_0000239
Summary

To date, all cases of this lethal disorder in cattle appear to be due to the same mutation, namely a nonsense mutation in the 5th of 9 exons of the ASS gene. Normal bovine ASS is a peptide containing 412 amino acids; the mutation occurs in the 86th codon.

Molecular Genetics

By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Dennis et al. (1989) reported the causative mutation as a C>T transition, altering arginine-86 (CGA) to a nonsense codon (TGA) (Mohammad Shariflou 10/11/2006; FN 19 Sept 2012).

Genetic Test

The .0001 mutation destroys a recognition sequence for the restriction enzyme AvaI, thereby generating an RFLP. Dennis et al. (1989) developed a PCR genotyping test based on this RFLP, with primers 100 bp on either side of the mutation site. After AvaI digestion of the PCR product, homozygous normals show a single 100-bp band (containing the fragments on either side of the mutation site), heterozygotes show a 100-bp band and a 200-bp band, and affected calves show a 200-bp band only. This test is now regularly performed on hair follicles, which are far easier to collect from the field than blood (Healy, pers. comm.).

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