Deficiency of uridine monophosphate synthase
- Phene ID
- 34
- Name
- Deficiency of uridine monophosphate synthase
- Phene Name
- Haplotype HHD
- OMIA ID
- 262
- Species ID
- 9913
- Characterised
- Yes
- Characterised Year
- 1993
| Symbol | Gene ID | Chromosome | Description |
|---|---|---|---|
| UMPS | 281568 | 1 | uridine monophosphate synthetase |
| Variant ID | Phenotype | Gene ID | Deleterious | Chromosome | Genomic | Transcript | Protein |
|---|---|---|---|---|---|---|---|
| 290 | Deficiency of uridine monophosphate synthase | 281568 | 1 | 1 | NC_037328.1:g.69151931C>T | NM_177508.1:c.1213C>T | NP_803474.1:p.(R405*) |
| Breed | Breed ID | Species ID | VBO Term |
|---|---|---|---|
| Holstein (black and white) (Cattle) | 39 | 9913 | http://purl.obolibrary.org/obo/VBO_0000237 |
| Holstein Friesian (Cattle) | 73 | 9913 | http://purl.obolibrary.org/obo/VBO_0000239 |
| Red Holstein, Switzerland (Cattle) | 243 | 9913 | http://purl.obolibrary.org/obo/VBO_0004501 |
| Wagyu (Cattle) | 33 | 9913 | http://purl.obolibrary.org/obo/VBO_0000422 |
This disorder is of particular interest in cattle, because it is one of the few cases in which an embryonic lethal has been identified. (By their very nature, embryonic lethals are difficult to identify; their only manifestation is a return to service.) To date, the only known cause of this disorder in cattle is a nonsense mutation in codon 405 of the UMPS gene, resulting in a complete deficiency of functional UMPS (Schwenger et al., 1993). Since nucleotides are required in such vast quantities during embryonic development, it is not surprising that homozygosity for the nonsense mutation results in embryonic death around 40 days in utero. The practical effect of this disorder is that carrier cows show a higher rate of return to service, because some of their pregnancies end in early natural abortion. Given that returns to service can have so many different causes, it would not have been possible to identify the mutation from reproductive records. How, then, was this embryonic lethal mutation detected initially? The answer is: by chance! As part of a nutrition study at the University of Illinois, the level of orotic acid was determined in the milk of cows in the university herd. Some cows had exceptionally high levels of this acid, and one possible explanation was that they were deficient in UMPS. Subsequent biochemical tests showed that these cows had only 50% of the normal activity of this enzyme (reviewed by Shanks and Robinson, 1990). Inheritance and molecular studies finally brought the whole story to light.
DUMPS is an autosomal recessive embryonic lethal.
By cloning and sequencing a very likely candidate gene (based on knowledge that the bovine disorder is due to deficiency of uridine monophosphate sythetase), Schwenger et al. (1993) identified a C>T transition in the bovine UMPS gene as a causal mutation.
Knowledge that the causal mutation removes a recognition sequence for the restriction enzyme AvaI immediately gave rise to a DNA test.