OMIA 000262-9913 : Deficiency of uridine monophosphate synthase in Bos taurus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 258900

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1993

Cross-species summary: Uridine monophosphate synthase (UMPS) is the enzyme responsible for converting orotic acid to uridine monophosphate (UMP), which is an essential component of pyrimidine nucleotides. This enzyme actually has two enzymatic functions: orotic phosphoribosyltransferase (OPRTase) and orotidine monophosphate decarboxylase (OMPDCase), corresponding to the last two steps in pyrimidine synthesis. Since pyrimidines are vital ingredients of nucleic acids, it follows that a deficiency of UMPS can have quite severe consequences.

Species-specific name: Haplotype HHD

Species-specific symbol: DUMPS; HHD

Species-specific description: 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.

Inheritance: DUMPS is an autosomal recessive embryonic lethal.

Mapping: The UMPS gene has been mapped to the middle of chromosome 1 (q31-36) (Barendse et al., 1993; Friedl and Rottmann, 1994; Ryan et al., 1994). [Compiled by Imke Tammen]

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 BTA1 at 55-73Mb (UMD 3.0 genome assembly).

Molecular basis: 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.

Clinical features: Carriers are phenotypically normal, but have only half the normal activity of uridine monophosphate synthase (Harden and Robinson, 1987). Also, during lactation, carriers excrete an elevated level of orotic acid in milk and urine (Robinson et al., 1984). Carrier x carrier matings require approximately 3.1 services per calving, compared to 2.0 for normal x normal matings. [Compiled by Imke Tammen]

Genetic testing: Knowledge that the causal mutation removes a recognition sequence for the restriction enzyme AvaI immediately gave rise to a DNA test.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
UMPS uridine monophosphate synthetase Bos taurus 1 NC_037328.1 (69127829..69177876) UMPS Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the required column headers

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Friesian Holstein Holstein-Friesian Red Holstein Waygu Deficiency of uridine monophosphate synthase UMPS nonsense (stop-gain) UMD 3.1 1 g.69756880C>T c.1213C>T p.R405* 1993 8486364 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; Breed information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)

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.
2018 Zepeda-Batista, J.L., Parra-Bracamonte, G.M., Núñez-Domínguez, R., Ramírez-Valverde, R., Ruíz-Flores, A. :
Screening genetic diseases prevalence in Braunvieh cattle. Trop Anim Health Prod :, 2018. Pubmed reference: 30014197. DOI: 10.1007/s11250-018-1655-y.
2011 Sun, D.X., Fan, X.H., Xie, Y., Chu, Q., Sun, Y., Zhang, Y., Zhang, S.L., Gong, W.J., Chen, S.H., Li, Y.H., Shi, W.H., Zhang, Y. :
Short communication: Distribution of recessive genetic defect carriers in Chinese Holstein. J Dairy Sci 94:5695-8, 2011. Pubmed reference: 22032394. DOI: 10.3168/jds.2011-4345.
VanRaden, P.M., Olson, K.M., Null, D.J., Hutchison, J.L. :
Harmful recessive effects on fertility detected by absence of homozygous haplotypes. J Dairy Sci 94:6153-61, 2011. Pubmed reference: 22118103. DOI: 10.3168/jds.2011-4624.
2010 Meydan, H., Yildiz, MA., Agerholm, JS. :
Screening for bovine leukocyte adhesion deficiency, deficiency of uridine monophosphate synthase, complex vertebral malformation, bovine citrullinaemia, and factor XI deficiency in Holstein cows reared in Turkey. Acta Vet Scand 52:56, 2010. Pubmed reference: 20929557. DOI: 10.1186/1751-0147-52-56.
2006 Ghanem, ME., Nakao, T., Nishibori, M. :
Deficiency of uridine monophosphate synthase (DUMPS) and X-chromosome deletion in fetal mummification in cattle. Anim Reprod Sci 91:45-54, 2006. Pubmed reference: 16310098. DOI: 10.1016/j.anireprosci.2005.03.008.
Patel, RK., Singh, KM., Soni, KJ., Chauhan, JB., Sambasiva Rao, KR. :
Lack of carriers of citrullinaemia and DUMPS in Indian Holstein cattle. J Appl Genet 47:239-42, 2006. Pubmed reference: 16877802.
2005 Kaminski, S., Grzybowski, G., Prusak, B., Rusc, A. :
No incidence of DUMPS carriers in Polish dairy cattle. J Appl Genet 46:395-7, 2005. Pubmed reference: 16278513.
1996 Harlizius, B., Schober, S., Tammen, I., Simon, D. :
Isolation of the bovine uridine monophosphate synthase gene to identify the molecular basis of DUMPS in cattle Journal of Animal Breeding & Genetics-Zeitschrift fur Tierzuchtung und Zuchtungsbiologie 113:303-309, 1996.
Poli, M.A., Dewey, R., Semorile, L., Lozano, M.E., Albarino, C.G., Romanowski, V., Grau, O. :
PCR screening for carriers of bovine leukocyte adhesion deficiency (BLAD) and uridine monophosphate synthase (DUMPS) in Argentine Holstein cattle Zentralblatt Fur Veterinarmedizin - Reihe A 43:163-168, 1996. Pubmed reference: 8693839.
1994 Friedl, R., Rottmann, O.J. :
Assignment of the Bovine Uridine Monophosphate Synthase Gene to the Bovine Chromosome Region 1Q34-36 by FISH Mammalian Genome 5:38-40, 1994. Pubmed reference: 8111127.
Kotze, A., Vanderwalt, S.I., Vorster, P.W. :
Incidence of UMP Synthase Deficiency in South African Holstein Cattle South African Journal of Animal Science - Suid - Afrikaanse Tydskrif Vir Veekunde 24:37-38, 1994.
Kuhn, M.T., Shanks, R.D. :
Association of Deficiency of Uridine Monophosphate Synthase with Production and Reproduction Journal of Dairy Science 77:589-597, 1994. Pubmed reference: 8182184. DOI: 10.3168/jds.S0022-0302(94)76988-5.
Ryan, A.M., Gallagher, D.S., Schober, S., Schwenger, B., Womack, J.E. :
Somatic cell mapping and in situ localization of the bovine uridine monophosphate synthase gene (UMPS) Mammalian Genome 5:46-47, 1994. Pubmed reference: 7906571.
Schwenger, B., Tammen, I., Aurich, C. :
Detection of the homozygous recessive genotype for deficiency of uridine monophosphate synthase by DNA typing among bovine embryos produced in vitro Journal of Reproduction and Fertility 100:511-514, 1994. Pubmed reference: 8021871.
1993 Barendse, W., Armitage, S.M., Ryan, A.M., Moore, S.S., Clayton, D., Georges, M., Womack, J.E., Hetzel, J. :
A genetic map of DNA loci on bovine chromosome 1 Genomics 18:602-608, 1993. Pubmed reference: 7905854.
Healy, P.J., Dennis, J.A. :
Inherited Enzyme Deficiencies in Livestock Veterinary Clinics of North America - Food Animal Practice 9:55-63, 1993. Pubmed reference: 8457930.
Robinson, J.L., Popp, R.G., Shanks, R.D., Oosterhof, A., Veerkamp, J.H. :
Testing for Deficiency of Uridine Monophosphate Synthase Among Holstein-Friesian Cattle of North America and Europe Livestock Production Science 36:287-298, 1993.
Schoeber, S., Simon, D., Schwenger, B. :
Sequence of the cDNA Encoding Bovine Uridine Monophosphate Synthase Gene 124:307-308, 1993. Pubmed reference: 8444356.
Schwenger, B., Schober, S., Simon, D. :
DUMPS Cattle Carry a Point Mutation in the Uridine Monophosphate Synthase Gene Genomics 16:241-244, 1993. Pubmed reference: 8486364. DOI: 10.1006/geno.1993.1165.
1992 Herzog, A. :
Genetic Defects in Cattle and the Possibilities of Control Wiener Tierarztliche Monatsschrift 79:142-148, 1992.
Schwenger, B., Schober, S., Simon, D. :
A TaqI Polymorphism at the Bovine Locus for Uridine Monophosphate Synthase (UMPS) Animal Genetics 23:82, 1992. Pubmed reference: 1570898.
Shanks, R.D., Greiner, M.M. :
Relationship Between Genetic Merit of Holstein Bulls and Deficiency of Uridine-5'-Monophosphate Synthase Journal of Dairy Science 75:2023-2029, 1992. Pubmed reference: 1500593. DOI: 10.3168/jds.S0022-0302(92)77962-4.
Shanks, R.D., Greiner, M.M. :
Relationship Between Genetic Merit of Holstein Bulls and Deficiency of Uridine-5'-Monophosphate Synthase (Journal of Dairy Science, Vol 75, Pg 2023, 1992) Journal of Dairy Science 75:3678, 1992.
Shanks, R.D., Popp, R.G., Mccoy, G.C., Nelson, D.R., Robinson, J.L. :
Identification of the Homozygous Recessive Genotype for the Deficiency of Uridine Monophosphate Synthase in 35-Day Bovine Embryos Journal of Reproduction & Fertility 94:5-10, 1992. Pubmed reference: 1552492.
1990 Anon. :
Hereditary Orotic Aciduria and Citrullinemia - Bovine Models Nutrition Reviews 48:193-195, 1990.
Counnotte, G.H.M., Smidt, W.J. :
Hereditary Ump Synthase Deficiency in Cattle Tijdschrift Voor Diergeneeskunde 115:958-959, 1990. Pubmed reference: 2281473.
Shanks, R.D. :
Reproductive Consequences of Deficiency of Uridine Monophosphate Synthase in Holstein Cattle American Journal of Veterinary Research 51:800-802, 1990. Pubmed reference: 2337281.
Shanks, R.D., Robinson, J.L. :
Deficiency of Uridine Monophosphate Synthase Among Holstein Cattle Cornell Veterinarian 80:119-122, 1990. Pubmed reference: 2318037.
1989 Shanks, R.D., Robinson, J.L. :
Embryonic Mortality Attributed to Inherited Deficiency of Uridine Monophosphate Synthase Journal of Dairy Science 72:3035-3039, 1989. Pubmed reference: 2625493. DOI: 10.3168/jds.S0022-0302(89)79456-X.
1987 Harden, K.K., Robinson, J.L. :
Deficiency of UMP synthase in dairy cattle: a model for hereditary orotic aciduria Journal of Inherited Metabolic Disease 10:201-209, 1987. Pubmed reference: 2448544.
Healey, M.H., Shanks, R.D. :
Performance of females heterozygous for deficiency of uridine monophosphate synthase Journal of Dairy Science 70:945-951, 1987. Pubmed reference: 3597935. DOI: 10.3168/jds.S0022-0302(87)80098-X.
Shanks, R.D., Bragg, D.S.A., Robinson, J.L. :
Deficiency of uridine monophosphate synthase in Holstein cattle: inheritance and body measurements Journal of Animal Science 64:695-700, 1987. Pubmed reference: 3571001.
Shanks, R.D., Bragg, D.S.A., Robinson, J.L. :
Incidence and inheritance of deficiency for uridine monophosphate synthase in Holstein bulls Journal of Dairy Science 70:1893-1897, 1987. Pubmed reference: 3668047. DOI: 10.3168/jds.S0022-0302(87)80228-X.
1986 Jones, L.R., Harden, K.K., Bragg, D.S.A., Robinson, J.L. :
Influence of age, sex, lactational state, and exogenous growth hormone on erythrocyte UMP synthase in dairy cattle Comparative Biochemical and Physiology B 84:489-495, 1986.
1984 Robinson, J.L., Dombrowski, D.B., Clark, J.H., Shanks, R.D. :
Oratate in milk and urine of dairy cows with a partial deficiency of uridine monophosphate synthase Journal of Dairy Science 67:1024-1029, 1984. Pubmed reference: 6547459. DOI: 10.3168/jds.S0022-0302(84)81401-0.
Robinson, J.L., Dombrowski, D.B., Harpestad, G.W., Shanks, R.D. :
Detection and prevalence of UMP synthase deficiency among dairy cattle. J Hered 75:277-80, 1984. Pubmed reference: 6547737.
Shanks, R.D., Dombrowski, D.B., Harpestad, G.W., Robinson, J.L. :
Inheritance of UMP synthase in dairy cattle Journal of Heredity 75:337-340, 1984. Pubmed reference: 6548235.
1983 Robinson, J.L., Drabik, M.R., Dombrowski, D.B., Clark, J.H. :
Consequences of UMP synthase deficiency in cattle. Proc Natl Acad Sci U S A 80:321-3, 1983. Pubmed reference: 6572893.

Edit History


  • Created by Mohammad Shariflou on 11 Nov 2006
  • Changed by Frank Nicholas on 14 Sep 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 29 Aug 2012
  • Changed by Frank Nicholas on 12 Jun 2013
  • Changed by Frank Nicholas on 24 Mar 2015