Deficiency Of Uridine Monophosphate Synthase Research Articles

Selected Monogenic Genetic Diseases in Holstein Cattle-A Review.

Genetic disorders arise from alterations in the hereditary information encoded in DNA, leading to potential detrimental effects on the well-being and vitality of organisms. Within the bovine population, genetic conditions inherited in an autosomal recessive manner are frequently associated with particular breeds. In recent years, several recessive haplotypes and a few causative mutations have been discovered in Holstein cattle: CDH (Holstein cholesterol deficiency), haplotypes with a homozygous deficiency in Holstein (HH1, HH3, HH4, HH5, HH6 and HH7), BLAD (bovine leukocyte adhesion deficiency) and DUMPS (deficiency of uridine monophosphate synthase). All of these diseases are inherited in an autosomal recessive manner. From a breeding perspective, recessive mutations specifically exhibit considerable detrimental effects and are a significant problem for breeders, exposing them to economic losses. Individual mutations can cause embryo death at any stage of pregnancy. Only genetic research and conscious selection of animals for mating will lead to a reduction in the number of carriers and elimination of mutations from the population.

Investigation of Some Autosomal Recessive Inherited Diseases (BLAD, DUMPS, CVM, and FXID) in Holstein Cattle

Genetic disorders are often transmitted via autosomal recessive inheritance, which negatively affect health, welfare, and yield traits in farm animals such as cattle. In this study, a total of 80 animals belonging to Holstein Friesian (HF) reared in the dairy farm of Akdeniz University were investigated in terms of Bovine Leukocyte Adhesion Deficieny (BLAD), Deficiency of Uridine Monophosphate Synthase (DUMPS), Factor XI Deficiency (FXID), and Complex Vertebral Malformation (CVM) via three molecular genotyping methods such as Polymerase Chain Reaction (PCR), PCR-Restriction Fragment Length Polymorphism (PCR-RFLP), and Allele-Sprcific PCR (AS-PCR). BLAD and DUMPS were analysed by PCR-RFLP, while PCR and AS-PCR were utilized to investigate FXID and CVM disorders, respectively. Based on fragment patterns on agarose gel electrophoresis, animals were genotyped as normal, mutant, and carrier. In this study, no carrier or mutant animals were detected for BLAD, CVM, DUMPS, and FXID diseases in HF cattle, since these animals were previously imported from disease-free dairy farms located in different provinces of Türkiye. Nevertheless, this population should be periodically checked for autosomal genetic disorders, since inherited diseases may be observed in the next generations due to causative mutations in the related genomic regions.

Hereditary orotic aciduria identified by newborn screening.

Introduction: Hereditary orotic aciduria is an extremely rare, autosomal recessive disease caused by deficiency of uridine monophosphate synthase. Untreated, affected individuals may develop refractory megaloblastic anemia, neurodevelopmental disabilities, and crystalluria. Newborn screening has the potential to identify and enable treatment of affected individuals before they become significantly ill. Methods: Measuring orotic acid as part of expanded newborn screening using flow injection analysis tandem mass spectrometry. Results: Since the addition of orotic acid measurement to the Israeli routine newborn screening program, 1,492,439 neonates have been screened. The screen has identified ten Muslim Arab newborns that remain asymptomatic so far, with DBS orotic acid elevated up to 10 times the upper reference limit. Urine organic acid testing confirmed the presence of orotic aciduria along with homozygous variations in the UMPS gene. Conclusion: Newborn screening measuring of orotic acid, now integrated into the routine tandem mass spectrometry panel, is capable of identifying neonates with hereditary orotic aciduria.

Frequency of genotypic markers for genetic disorders, colour, polledness, and major genes in Blanco Orejinegro cattle.

The purpose of this work was to establish DNA marker frequencies for genetic disorders, colour, horned/polled trait, and major genes of importance for productive and reproductive traits in Blanco Orejinegro (BON) cattle. The Blanco Orejinegro breed is a Colombian creole breed characterized by a white hair coat on black skin with black ears, black hair on the middle part of the legs, and absence of horns. We genotyped 420 animals of Colombia, 70 with the GGP-Bovine 150K chip and 350 with the GGP-Bovine 50K chip. The markers were associated with 50 genetic diseases, 52 major gene variants related to productive traits, and 12 variants related to coat coloration, presence of horns, and adaptation, selected from the information contained in the chips. Genotype frequencies were estimated using the R statistical program. Genetic disorder annotations were derived using the Online Mendelian Inheritance in Animals tool (OMIA) and the average inbreeding coefficient (F) (n = 7799) using the MTDFNRM program. Carriers were found for 16 of the genetic disorders evaluated but with low frequencies (0.24 to 2.46%); no homozygous animals were found for the disorders. Carriers were associated with disorders such as bovine leukocyte adhesion deficiency (BLAD), deficiency of uridine monophosphate synthase (DUMPS), syndactyly, and epidermolysis bullosa (EB). The F was 4.41%. Concerning the genes associated with colour (TYR, MC1R, and PMEL), alleles related to black pigmentation, the absence of horns (polledness), and slick coat (an adaptive trait) were highly frequent (> 81.90%). Markers associated with milk production and quality, yellow fat, and fertility showed variable frequencies, indicating selection potential. Allele frequency of genetic disorders in BON cattle was low, suggesting few genetic disorder problems, with syndactyly being the most frequent condition. The markers associated with colour and polledness were almost fixed, with a frequency at or near 100%. Production and reproduction markers showed variability for selection.

Novel mutation in UMPS gene leads to false positive result of DUMPS (genetic disorder) in buffaloes: need for gene sequencing before confirming results of RFLP in new species

Deficiency of uridine monophosphate synthase (DUMPS) is a lethal genetic disorder associated with early embryonic mortality. Murrah and Mehsana male buffaloes (n = 594) were screened for DUMPS by PCR-RFLP technique. A few Murrah buffalo male calves were found to be carriers of DUMPS in RFLP, which has not been reported earlier. On the Sanger sequencing, a novel A to G substitution mutation was identified in AvaI restriction recognition site of UMPS gene in buffaloes. This mutation hinders digestion of DNA by AvaI which leds to false positive results for DUMPS carrier in RFLP. The results indicated that genome sequencing must be performed before confirming results of RFLP in any new species. All the buffaloes that were tested had only wild-type genotype in exon 5 for DUMPS specific allele.

Simultaneous Genetic Screening of Bovine Leukocyte Adhesion Deficiency, Complex Vertebral Malformation, Deficiency of Uridine Monophosphate Synthase, and Mule foot in Holstein Cows in Taiwan

Simultaneous Genetic Screening of Bovine Leukocyte Adhesion Deficiency, Complex Vertebral Malformation, Deficiency of Uridine Monophosphate Synthase, and Mule foot in Holstein Cows in Taiwan

Występowanie chorób genetycznych (BLAD, DUMPS) w polskiej populacji bydła rasy holsztyńsko-fryzyjskiej

BLAD (bovine leukocyte adhesion deficiency) and DUMPS (deficiency of uridine monophosphate synthase) are hereditary lethal autosomal recessive disorders that may affect Holstein cattle. The aim of the present study was to evaluate the frequency of BLAD and DUMPS genotypes in the Polish population of dairy cows. In the study 5 732 Polish Holstein-Friesian females were genetically tested for BLAD and DUMPS. Results of the present study indicate that the Polish population of dairy cattle is free from DUMPS as there were not carriers nor sick animals. For BLAD the study confirmed the present of carriers in the population to be at a low value (0.21%). Both BLAD and DUMPS may strongly affect the profitability of a dairy farm, therefore, in order to avoid the economic losses caused by the presence of these genetic disorders in the herd it is important to screen the population and detect carriers as soon as possible.

Genetic Screening of Deficiency of Uridine Monophosphate Synthase (Dumps), Bovine Citrullinaemia (BC) and Factor Xi Deficiency (Fxid) in Hardhenu, Sahiwal and Hariana Bulls

Genetic Screening of Deficiency of Uridine Monophosphate Synthase (Dumps), Bovine Citrullinaemia (BC) and Factor Xi Deficiency (Fxid) in Hardhenu, Sahiwal and Hariana Bulls

Genetic analysis of orotic acid predicted with Fourier transform infrared milk spectra

Fourier transform infrared spectral analysis is a cheap and fast method to predict milk composition. A not very well studied milk component is orotic acid. Orotic acid is an intermediate in the biosynthesis pathway of pyrimidine nucleotides and is an indicator for the metabolic cattle disorder deficiency of uridine monophosphate synthase. The function of orotic acid in milk and its effect on calf health, health of humans consuming milk or milk products, manufacturing properties of milk, and its potential as an indicator trait are largely unknown. The aims of this study were to determine if milk orotic acid can be predicted from infrared milk spectra and to perform a large-scale phenotypic and genetic analysis of infrared-predicted milk orotic acid. An infrared prediction model for orotic acid was built using a training population of 292 Danish Holstein and 299 Danish Jersey cows, and a validation population of 381 Danish Holstein cows. Milk orotic acid concentration was determined with nuclear magnetic resonance spectroscopy. For genetic analysis of infrared orotic acid, 3 study populations were used: 3,210 Danish Holstein cows, 3,360 Danish Jersey cows, and 1,349 Dutch Holstein Friesian cows. Using partial least square regression, a prediction model for orotic acid was built with 18 latent variables. The error of the prediction for the infrared model varied from 1.0 to 3.2 mg/L, and the accuracy varied from 0.68 to 0.86. Heritability of infrared orotic acid predicted with the standardized prediction model was 0.18 for Danish Holstein, 0.09 for Danish Jersey, and 0.37 for Dutch Holstein Friesian. We conclude that milk orotic acid can be predicted with moderate to good accuracy based on infrared milk spectra and that infrared-predicted orotic acid is heritable. The availability of a cheap and fast method to predict milk orotic acid opens up possibilities to study the largely unknown functions of milk orotic acid.

HIGH- RESOLUTION MELTING (HRM) CURVE ANALYSIS: NEW APPROACH USED TO DETECT BLAD AND DUMPS IN URUGUAYAN HOLSTEIN BREED

The widespread use of artificial insemination has allowed the expansion of genetic progress. However, it also brought consequences such as the expansion of lethal hereditary diseases and the increase in inbreeding. The object of this study was to establish a fast and sensitive molecular assay to detect bovine leukocyte adhesion deficiency (BLAD) and deficiency of uridine monophosphate synthase (DUMPS) carriers in Uruguayan Holstein cattle by means of high resolution melting (HRM) curve analysis. By testing previously confirmed carrier and non-carrier animals, we set up a rapid, simple, and inexpensive diagnostic test using PCR followed by HRM curve analysis. The PCR-HRM genotyping method was effective for the discrimination of BLAD and DUMPS homozygous genotypes, and the BLAD heterozygous genotype. We conclude that the PCR-HRM assay is a robust, reliable, and economical tool for the detection of these mutations in the Holstein breed, which may be implemented in genetic selection programs.

Screening genetic diseases prevalence in Braunvieh cattle.

Heritable abnormalities can cause a reduction in productive performance, structural defects, or death of the animal. There are reports of hereditary abnormalities in Braunvieh cattle from several countries, but no evidence was found on their existence in Mexico. In this study, 28 genes associated with hereditary diseases were screened with the GGP-LD 30K array (GeneSeek®) in 300 Mexican registered Braunvieh animals. Allelic frequencies of the markers associated with illness were obtained for the following: citrullinaemia, spinal dysmyelination, spinal muscular atrophy, Brows Swiss fertility haplotype 2, congenital muscular dystonia, epidermolysis bullosa, Pompes, maple syrup urine, syndactyly, Weaver syndrome, crooked tail, deficiency of uridine monophosphate synthase, hypotrichosis, Marfan syndrome, and weak calf syndrome. The allelic frequency values were low for all the analysed loci (from 0.0015 to 0.0110), with exception of syndactyly (0.4145). Although homozygous animals for these genetic conditions were detected, no physical or physiological abnormalities associated with the clinical form of the diseases were observed in the sampled animals. Markers associated with a crooked tail, deficiency of uridine monophosphate synthase, hypotrichosis, Marfan syndrome, and weak calf syndrome were absent. The studied Mexican Braunvieh population does not present clinical or subclinical effects for ten diseases in homozygous animals. However, since the assessed animals are considered as breeding stock, the monitoring of carrier animals might be periodically necessary.

MODERN MOLECULAR-GENETIC APPROACH TO INCREASE EFFICIENCY OF SELECTION PROCESS IN ANIMAL BREEDING OF UKRAINE

MODERN MOLECULAR-GENETIC APPROACH TO INCREASE EFFICIENCY OF SELECTION PROCESS IN ANIMAL BREEDING OF UKRAINE

Genetic Screening of Deficiency of Uridine Monophosphate Synthase in Holstein Freisian Crossbred Cattle

Fifty Holstein Friesian (H.F) crossbredcattle were screened for Deficiency of Uridine Monophosphate Synthase (DUMPS) using PCR-RFLP. Blood samples were collected from jugular veins in 2 ml capacity vaccutainers containing 2 mg/ml (K2 EDTA). DNA was isolated from the blood samples by using whole blood extraction kit. PCR was performed for amplification of polymorphic region of Uridine Monophosphate Synthase (UMPS) gene (108 bp) on bovine chromosome 1. The PCR products of 108 bp were digested with AvaI endonuclease enzyme. The normal allele in unaffected cattle produced three fragments of 53 bp, 36 bp and 19 bp. No animal was found carrier for UMPS gene. The genotype frequency of normal individuals and the gene frequency of normal allele were found to be one.

Screening for bovine leukocyte adhesion deficiency, deficiency of uridine monophosphate synthase, bovine citrullinaemia and factor XI deficiency in Holstein cattle

Holstein cattle reared in Eskisehir region were monitored with respect to the genetic disorders defined as bovine leukocyte adhesion deficiency (BLAD), deficiency of uridine monophosphate synthase (DUMPS), bovine citrullinaemia (BC) and factor XI deficiency (FXID). To determine the presence of BLAD, DUMPS, BC and FXID genotypes, Holstein cattle (219) were sampled. Three BLAD and 2 FXID carriers were identified among the 219 Holstein cattle examined, while none of the cows carried DUMPS and BC. Current study demonstrated that carriers of BLAD and FXID are present in the Turkish Holstein population in Eskisehir region, although at a low frequency. Since, artificial insemination is widely used in these populations, determination of the carriers of hereditary disorders within the population of breeding sires has become essential. To prevent economic losses resulting from genetic disorders, it is advised to screen breeding sires for these genotypes. The aim of this study was to investigate existence and prevalence of BLAD, DUMPS, BC and FXID alleles in Holstein cattle reared in Eskisehir region by using PCR and PCR-RFLP methods.

Genetic disorders in dairy cattle: An Indian perspective

Genetic diseases have always been present in the animal population but their significance has increased in recent decades. In some breeds, the occurrence of inherited anomalies has become frequent and economically important. Some of autosomal recessive disorders are Holstein specific. The present review article describes prevalence of the most important autosomal recessive disorders in Holstein and its crossbreds as compared to their occurrence worldwide. Mainly five disorders namely, bovine leukocyte adhesion deficiency (BLAD), deficiency of uridine monophosphate synthase (DUMPS), bovine citrullinaemia, complex vertebral malformation (CVM) and factor XI (FXI) deficiency syndrome, are being screened in Indian Holstein and its crossbred cattle with the major objective to reduce the incidence of genetic disorders in cattle population and reduce the economic losses to the organized farms. Detection of heterozygote carriers enables their selection, and therefore, the control and prevention of the spread of recessive diseases in the population.

Estimating allele frequencies of some hereditary diseases in Holstein cattlereared in Burdur Province, Turkey

The economics of dairy cattle breeding around the world has been significantly affected by the autosomal recessive hereditary diseases of bovine leukocyte adhesion deficiency (BLAD), factor XI deficiency (FXID), bovine citrullinemia (BC), and deficiency of uridine monophosphate synthase (DUMPS). The aim of this study was to determine BLAD, FXID, BC, and DUMPS alleles in Holstein cattle raised in Burdur Province in Turkey. This study involved taking blood samples randomly from 500 head of Holstein cattle at various dairy farms in different towns in Burdur Province. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis was employed to identify cows with these diseases. The results showed that the percentages of carrier animals for BLAD and FXID were 2% and 1.8%, respectively, while no DUMPS or BC was found in the study population. This is the first study on BLAD, FXID, BC, and DUMPS in Holstein cattle raised in Burdur Province in Turkey.

Identification of a Nonsense Mutation in CWC15 Associated with Decreased Reproductive Efficiency in Jersey Cattle

With the recent advent of genomic tools for cattle, several recessive conditions affecting fertility have been identified and selected against, such as deficiency of uridine monophosphate synthase, complex vertebral malformation, and brachyspina. The current report refines the location of a recessive haplotype affecting fertility in Jersey cattle using crossover haplotypes, discovers the causative mutation using whole genome sequencing, and examines the gene’s role in embryo loss. In an attempt to identify unknown recessive lethal alleles in the current dairy population, a search using deep Mendelian sampling of 5,288 Jersey cattle was conducted for high-frequency haplotypes that have a deficit of homozygotes at the population level. This search led to the discovery of a putative recessive lethal in Jersey cattle on Bos taurus autosome 15. The haplotype, denoted JH1, was associated with reduced fertility, and further investigation identified one highly-influential Jersey bull as the putative source ancestor. By combining SNP analysis of whole-genome sequences aligned to the JH1 interval and subsequent SNP validation a nonsense mutation in CWC15 was identified as the likely causative mutation underlying the fertility phenotype. No homozygous recessive individuals were found in 749 genotyped animals, whereas all known carriers and carrier haplotypes possessed one copy of the mutant allele. This newly identified lethal has been responsible for a substantial number of spontaneous abortions in Jersey dairy cattle throughout the past half-century. With the mutation identified, selection against the deleterious allele in breeding schemes will aid in reducing the incidence of this defect in the population. These results also show that carrier status can be imputed with high accuracy. Whole-genome resequencing proved to be a powerful strategy to rapidly identify a previously mapped deleterious mutation in a known carrier of a recessive lethal allele.

Monitoring of BLAD, DUMPS, CVM, BC and FXID in Turkish native cattle breeds

Bu çalışmada, Türkiye yerli sığır ırkları Sığır Lökosit Bağlanma Yetersizliği (BLAD), Üridin Monofosfat Sentezi Yetersizliği (DUMPS), Kompleks Omurga Deformasyonu (CVM), Sığır Sitrülin Birikimi (BC) ve Faktör XI Eksikliği (FXID) genetik kusurları bakımından tanımlanmıştır. Otozamal kromozomlar üzerinde bulunan resesif genlerle belirlenmekte olan bu genetik kusurlar büyük ekonomik kayıplara neden olmaktadır. Araştırmada, Yerli Kara (200 baş), Doğu Anadolu Kırmızısı (100 baş), Boz ırk (100 baş), Güneydoğu Anadolu Sarısı (50 baş), Güneydoğu Anadolu Kırmızısı (50 baş) ve Zavot (9 baş) ırklarına ait toplam 509 baş sığır materyal olarak kullanılmıştır. Genomik DNA kandan elde edilmiş ve polimeraz zincir reaksiyonu (PCR) yöntemi ile üzerinde durulan genetik kusurlara ait gen bölgeleri çoğaltılmıştır. PCR ürünleri TaqI (BLAD), AvaI (DUMPS), EcoT22I (CVM) ve AvaII (BC) restriksiyon enzimleri ile muamele edilerek sığırların genotipleri agaroz jel elektroforez yöntemiyle belirlenmiştir. FXID genetik kusuru bakımından sığırların genotipleri ise sadece PCR ürünlerinin agaroz jel elektroforez yöntemindeki bant modelleri kullanılarak tespit edilmiştir. Araştırmada, incelenen 509 baş sığırdan hiçbirinin BLAD, DUMPS, CVM, BC ve FXID genetik kusurlarının taşıyıcısı olmadığı saptanmıştır. Bu araştırmanın sonuçlarına göre, BLAD, DUMPS, CVM, BC ve FXID mutant allellerinin Türkiye yerli sığır ırklarında bulunmadığı söylenebilir.

Short communication: Distribution of recessive genetic defect carriers in Chinese Holstein

In dairy cattle, 4 important recessive hereditary diseases exist: complex vertebral malformation (CVM), bovine leukocyte adhesion deficiency (BLAD), citrullinemia (CTLN), and deficiency of uridine monophosphate synthase (DUMPS). Holstein Associations in developed countries have established monitoring systems for such disorders in Holstein bulls for decades. Over the past decades, China has continuously imported Holstein semen and embryos, mainly from North America but also from Europe. The dissemination of such genetic defects was undetermined until now, although efforts were taken to develop molecular techniques and detect carriers for CVM and BLAD in small populations of Chinese dairy cattle. Thus, herein we extensively screened 732 proven bulls participating in artificial insemination programs and 136 young bulls entering progeny test from 15 bull stations in China for CVM, BLAD, CTLN, and DUMPS. The proportion of carriers of the defects was found to be 7.72, 1.38, 0.23, and 0.12%, respectively. Given our findings, early diagnostic and monitoring systems on recessive inherited disorders among proven and young bulls entering the national genetic improvement programs for dairy cattle of China should be established immediately, in which a series of measures will be taken to prevent further spreading of such disorders and gradually eliminate them in the dairy cattle population in China.

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

BackgroundBovine leukocyte adhesion deficiency (BLAD), deficiency of uridine monophosphate synthase (DUMPS), complex vertebral malformation (CVM), bovine citrullinaemia (BC) and factor XI deficiency (FXID) are autosomal recessive hereditary disorders, which have had significant economic impact on dairy cattle breeding worldwide. In this study, 350 Holstein cows reared in Turkey were screened for BLAD, DUMPS, CVM, BC and FXID genotypes to obtain an indication on the importance of these defects in Turkish Holsteins.MethodsGenomic DNA was obtained from blood and the amplicons of BLAD, DUMPS, CVM, BC and FXID were obtained by using PCR. PCR products were digested with TaqI, AvaI and AvaII restriction enzymes for BLAD, DUMPS, and BC, respectively. These digested products and PCR product of FXID were analyzed by agarose gel electrophoresis stained with ethidium bromide. CVM genotypes were detected by DNA sequencing. Additionally, all genotypes were confirmed by DNA sequencing to determine whether there was a mutant allele or not.ResultsFourteen BLAD, twelve CVM and four FXID carriers were found among the 350 Holstein cows examined, while carriers of DUMPS and BC were not detected. The mutant allele frequencies were calculated as 0.02, 0.017, and 0.006 for BLAD, CVM and FXID, respectively with corresponding carrier prevalence of 4.0% (BLAD), 3.4% (CVM) and 1.2% (FXID).ConclusionThis study demonstrates that carriers of BLAD, CVM and FXID are present in the Turkish Holstein population, although at a low frequency. The actual number of clinical cases is unknown, but sporadic cases may appear. As artificial insemination is widely used in dairy cattle breeding, carriers of BLAD, CVM and FXID are likely present within the population of breeding sires. It is recommended to screen breeding sires for these defective genes in order to avoid an unwanted spread within the population.