OMIA 001819-9913 : Xanthinuria, type II in Bos taurus

In other species: dog

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 603592 (trait) , 613274 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2000

Cross-species summary: Animals with hereditary xanthinuria (excretion of large amounts of xanthine in the urine) may be asymptomatic, may have subclinical uroliths (xanthine stones), or present with clinical signs of urolithiasis. Urolith formation can be influenced by other biologic and environmental factors such as sex, diet and urine properties. Xanthinuria, type I (OMIA002445) is caused by variation in the XDH gene and xanthinuria, type II (OMIA 001819) is caused by variation in the MOCOS gene. Information relating to xanthinuria without identified causal variants is listed under xanthinuria, generic (OMIA 001283).

History: This disorder was first reported in cattle by Mizoguchi (1997).

Inheritance: Pedigree analysis by Watanabe et al. (2000) revealed autosomal recessive inheritance in Japanese Black cattle. Similar evidence was reported for Tyrolean Grey cattle by Murgiano et al. (2016).

Mapping: By conducting a genome scan on 21 affected offspring and their parents (21 dams and two sires), each genotyped with 200 microsatellites, Watanabe et al. (2000) linkage-mapped this disorder to the "centromeric region of bovine chromosome (BTA) 24". They then FISH-mapped the most likely comparative candidate gene (based on the most likely causative gene in humans), namely Drosophila ma-l orthologue (encoding the putative molybdopterin cofactor sulfurase, which is required for normal activity of both XDH and AO; see Clinical section), to "BTA24q13.1–13.3", which corresponds to the linkage-mapped location of the disorder locus.

Molecular basis: Cloning and sequencing of the bovine gene encoding molybdopterin cofactor sulfurase (MCSU, now called MOCOS) in normal and affected cattle, by Watanabe et al. (2000), revealed the causal mutation to be a 3bp deletion (c.769_771delTAC) of codon 257 (deleting Tyr) in the MOCOS gene.

Murgiano et al. (2016) discovered a different mutation in the MUCOS gene as the likely cause in Tyrolean Grey cattle: "1 bp deletion in the molybdenum cofactor sulfurase (MOCOS) gene (g.21222030delC; c.1881delG and c.1782delG), located in an 11 Mb region of homozygosity on BTA 24)".

Clinical features: As reported by Watanabe et al. (2000), this disorder is "characterized by elevated xanthine secretion in the urine associated with lethal growth retardation at approximately 6 months of age . . . Affected cattle had expanded renal tubules containing xanthine calculi ranging from 1–3 mm in diameter". A diagnostic feature is the lack of xanthine dehydrogenase (XDH) and aldehyde oxidase (AO).

Prevalence: Watanabe et al. (2000) "confirmed that more than 300 xanthinuria-affected [Japanese Black] cattle have been recorded over the last 20 years and that all parents were descendants of a putative founder sire. Affected male, female, and unknown offspring numbered 177, 148, and 9, respectively." Bhati et al. (2020) reported that two Braunvieh "ancestor bulls born in 1967 and 1974 ... were heterozygous carriers of a single base pair deletion (BTA24:g.21222030delC) in the MOCOS gene that causes xanthinuria in the homozygous state in Tyrolean grey cattle."

Breed: Japanese Black.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MOCOS molybdenum cofactor sulfurase Bos taurus 24 NC_037351.1 (20946894..20886491) MOCOS Homologene, Ensembl, NCBI gene

Variants

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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
492 Tyrolean Grey Xanthinuria, type II MOCOS deletion, small (<=20) Naturally occurring variant ARS-UCD1.2 24 g.20911933del c.1881del p.(S628Vfs9*) Published using UMD3.1 position: g.21222030delC; cDNA and protein positions are given transcript: ENSBTAT00000048768. Positions for a second transcript (ENSBTAT00000065375) were given in the paper: c.1782del and p.(S595Vfs9*). 2016 27919260 The genomic location on ARS-UCD1.2 was determined by Katie Eager and Shernae Woolley, EMAI, NSW. Department of Primary Industries.
446 Japanese Black Xanthinuria, type II MOCOS deletion, small (<=20) Naturally occurring variant ARS-UCD1.2 24 g.20936257_20936259del c.769_771del p.(Y257del) published as c.769_771delTAC 2000 10801779 The genomic location on ARS-UCD1.2 was determined by Katie Eager and Shernae Woolley, EMAI, NSW. Department of Primary Industries.

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.
2020 Bhati, M., Kadri, N.K., Crysnanto, D., Pausch, H. :
Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data. BMC Genomics 21:27, 2020. Pubmed reference: 31914939. DOI: 10.1186/s12864-020-6446-y.
2016 Murgiano, L., Jagannathan, V., Piffer, C., Diez-Prieto, I., Bolcato, M., Gentile, A., Drögemüller, C. :
A frameshift mutation in MOCOS is associated with familial renal syndrome (xanthinuria) in Tyrolean Grey cattle. BMC Vet Res 12:276, 2016. Pubmed reference: 27919260. DOI: 10.1186/s12917-016-0904-4.
2000 Watanabe, T., Ihara, N., Itoh, T., Fujita, T., Sugimoto, Y. :
Deletion mutation in Drosophila ma-l homologous, putative molybdopterin cofactor sulfurase gene is associated with bovine xanthinuria type II. J Biol Chem 275:21789-92, 2000. Pubmed reference: 10801779. DOI: 10.1074/jbc.C000230200.
1997 Mizoguchi, H. :
Livestock Technology (Japan) 509:2-6, 1997.

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