Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Citrullinemia is an inborn error of metabolism due to deficiency of the urea cycle enzyme, argininosuccinate synthetase [L-citrulline:L-aspartate ligase (AMP-forming), EC 6.3.4.5]. The disease was first described in humans but was recently reported in dairy cattle in Australia. Here we report the nucleotide sequence of the normal bovine cDNA for argininosuccinate synthetase and the mutation present in animals with citrullinemia. Analysis of DNA from affected animals by Southern blotting did not readily identify the mutation in the bovine gene. RNA (Northern) blotting revealed a major reduction in the steady-state amount of mRNA in the liver of affected animals to less than 5% of controls. The bovine cDNA was cloned and sequenced and revealed 96% identity with the deduced human sequence at the amino acid level. Starting with mutant bovine liver, the mRNA was reverse-transcribed; the cDNA product was amplified with the polymerase chain reaction, cloned, and sequenced. The sequence revealed a C----T transition converting arginine-86 (CGA) to a nonsense codon (TGA). A second C----T transition represented a polymorphism in proline-175 (CCC----CCT). The mutation and the polymorphism were confirmed by amplification of genomic DNA and demonstration with restriction endonuclease enzymes of both the loss of an Ava II site in DNA from mutant animals at codon 86 and the presence or absence of a Dde I site at codon 175. The loss of the Ava II site can be used for rapid, economical, nonradioactive detection of heterozygotes for bovine citrullinemia.
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PMID:Molecular definition of bovine argininosuccinate synthetase deficiency. 281 70

A cytogenetically detectable deletion in the area of Yq11 has been demonstrated in some men with spermatogenic arrest, leading to the suggestion that a spermatogenic factor(s) lies within this region. The probe pAS1 detects an argininosuccinate synthetase pseudogene 6 (ASSP6), which has been mapped to Ycen-q11. The 4B-2 (DYS 15) probe detects a single-copy 3.3 kb EcoRI fragment that maps to the proximal portion of the Y long arm located distal to the sequence detected by the pAS1 probe. Deoxyribonucleic acid (DNA) samples from normal males and females and ten males with spermatogenic arrest were digested with the restriction endonuclease EcoRI, electrophoresed on agarose gels, Southern blotted, and hybridized with the pAS1 and 4B-2 probes. All males tested, including the ten azoospermic males with spermatogenic arrest, exhibited 4.3 kb and 3.3 kb male specific fragments with the pAS1 and 4B-2 probes, respectively. From preliminary analyses, the authors conclude that the regions detected by these two probes are not absent in these azoospermic males and that the cause of their spermatogenic arrest may not involve deletion within this region. Molecular defects affecting spermatogenesis may involve loss of sequences at Yq11, which were not tested in the study, or they may derive from heterogenous causes.
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PMID:Use of deoxyribonucleic acid probes to test for Yq11 deletions in males with spermatogenic arrest. 282 95

Six Friesian calves from a pedigree herd died or were killed within 1 week of birth because of progressive central nervous disease in which the only consistent lesion was cerebral oedema. The cause was citrullinaemia, resulting from an autosomally inherited dysfunction of the urea cycle enzyme arginosuccinate synthetase. Citrullinaemia was diagnosed by demonstrating markedly elevated concentrations of citrulline in the blood of one calf and in the cerebral spinal fluid of another. One of two sires used in the herd was a heterozygous carrier of the disease. Heterozygocity was demonstrated using a polymerase chain reaction/restriction endonuclease test designed to detect the genetic mutation that causes citrullinaemia in cattle.
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PMID:Citrullinaemia in Friesian calves. 1603 42