Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recent association study suggested that the His113 variant of microsomal epoxide hydrolase (mEPHX) may confer a risk for development of emphysema, presumably by increasing susceptibility to smoking injury. Before considering a possible role of this enzyme in pulmonary disease, we attempted to characterize the genetic polymorphism further. The Tyr/His113 polymorphism within exon 3 of mEPHX was initially examined in 62 healthy individuals by conventional methods involving polymerase chain reaction (PCR)-based determination of a restriction fragment length polymorphism (RFLP). Genomic nucleotide sequences, including the polymorphic site and the downstream primer sequence, were further analyzed in 95 unrelated, healthy Japanese volunteers by single-stranded conformation polymorphism (SSCP) analysis and direct sequencing. Genotyping by the first method (PCR-RFLP) revealed that the allelic distribution in our test population apparently deviated from Hardy-Weinberg equilibrium. Sequence analysis showed that a synonymous nucleotide substitution, AAG to AAA (Lys119), was located just within the published primer site. The AAA at codon 119 was present only in alleles with Tyr113, and its frequency reached 0.31 in our panel of 190 Japanese alleles. This substitution potentially hampered PCR amplification because of the nucleotide mismatch, with the result that the frequency of the Tyr113 variation was underestimated. The frequency of His113, a possible emphysema susceptibility allele of the mEPHX gene, was thus overestimated when human DNA samples were genotyped in the conventional way. Depending on the population(s) tested, this anomaly could represent a pitfall for PCR-based association studies.
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PMID:Overestimated frequency of a possible emphysema-susceptibility allele when microsomal epoxide hydrolase is genotyped by the conventional polymerase chain reaction-based method. 1128 20

A number of trinucleotide sequences in DNA can form compact and stable hairpin loops that may have significance for DNA replication and transcription. The conformational analysis of these motifs is important for an understanding of the function and design of nucleic acid structures. Extensive conformational searches have been performed on three experimentally known trinucleotide hairpin loops (AGC, AAA, and GCA) closed by a four-base-pair stem. An implicit solvation model based on the generalized Born method has been employed during energy minimization and conformational search. In addition, energy-minimized conformers were evaluated using a finite-difference Poisson-Boltzmann approach. For all three loop sequences, conformations close to experiment were found as lowest-energy structures among several thousand alternative energy minima. The inclusion of reaction-field contributions was found to be important for a realistic conformer ranking. Most generated hairpin loop structures within approximately 5 kcal x mol(-1) of the lowest-energy structure have a similar topology. Structures within approximately 10 kcal x mol(-1) could be classified into about five structural families representing distinct arrangements of loop nucleotides. Although a large number of backbone torsion angle combinations were compatible with each structural class, some specific patterns could be identified. Harmonic mode analysis was used to account for differences in conformational flexibility of low-energy sub-states. Class-specific differences in the pattern of atomic fluctuations along the sequence were observed; however, inclusion of conformational entropy contributions did not change ranking of structural classes. For an additional loop sequence (AAG) with no available experimental structure, the approach suggests a lowest-energy loop topology overall similar to the other three loop sequences but closed by a different non-canonical base-pairing scheme.
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PMID:Conformational analysis of DNA-trinucleotide-hairpin-loop structures using a continuum solvent model. 1132 35

A 30-year-old female who is homozygous for a Hb E-like abnormal hemoglobin and her immediate relatives were studied. Clinical examination of the proband revealed no abnormality. Routine hematological analysis showed that her hemoglobin level was 12 g/dL, MCV 82 fL, MCH 28 pg, RDW 15%. DNA sequence analysis indicated the presence of a G-->A substitution at codon 22 corresponding to an abnormal hemoglobin, namely Hb E-Saskatoon [beta22(B4)Glu-->Lys (GAA-->AAA)]. Absence of any abnormalities in clinical and routine hematological investigations of the homozygous patient indicated that the phenotypical expression of the Hb E-Saskatoon is very mild. Using a reverse transcription-polymerase chain reaction technique, the alpha/beta and betaX/betaA-mRNA (X = Hb E-Saskatoon) ratios were determined. Normal alpha/beta and betaX/betaA-mRNA ratios were found in the homozygous patient and in all heterozygotes, indicating that the respective mutation did not alter the stability of the mRNA. FokI restriction enzyme analysis of the polymerase chain reaction products obtained from the genomic DNA and/or beta-globin mRNA made it possible for rapid diagnosis of Hb E-Saskatoon, and for its differentiation from Hb E [beta26(B8)Glu-->Lys (GAG-->AAG)]. Analysis of the restriction fragment length polymorphism (RFLP) in the beta-globin gene complex of the index patient and of another unrelated family with a compound heterozygosity for Hb E-Saskatoon and beta-thalassemia revealed that the Hb E-Saskatoon mutation shared a common allele.
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PMID:Homozygosity for Hb E-Saskatoon [beta22(B4)Glu-->Lys] in a Turkish patient. 1179 74

Transfer RNA molecules translate the genetic code by recognizing cognate mRNA codons during protein synthesis. The anticodon wobble at position 34 and the nucleotide immediately 3' to the anticodon triplet at position 37 display a large diversity of modified nucleosides in the tRNAs of all organisms. We show that tRNA species translating 2-fold degenerate codons require a modified U(34) to enable recognition of their cognate codons ending in A or G but restrict reading of noncognate or near-cognate codons ending in U and C that specify a different amino acid. In particular, the nucleoside modifications 2-thiouridine at position 34 (s(2)U(34)), 5-methylaminomethyluridine at position 34 (mnm(5)U(34)), and 6-threonylcarbamoyladenosine at position 37 (t(6)A(37)) were essential for Watson-Crick (AAA) and wobble (AAG) cognate codon recognition by tRNA(UUU)(Lys) at the ribosomal aminoacyl and peptidyl sites but did not enable the recognition of the asparagine codons (AAU and AAC). We conclude that modified nucleosides evolved to modulate an anticodon domain structure necessary for many tRNA species to accurately translate the genetic code.
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PMID:Accurate translation of the genetic code depends on tRNA modified nucleosides. 1186 49

Translating ribosomes can shift reading frame at specific sites with high efficiency for gene expression purposes. The most common type of shift to the -1 frame involves a tandem realignment of two anticodons from pairing with mRNA sequence of the form X XXY YYZ to XXX YYY Z where the spaces indicate the reading frame. The predominant -1 shift site of this type in eubacteria is A AAA AAG. The present work shows that in Escherichia coli the identity of the 6 nt 3' of this sequence can be responsible for a 14-fold variation in frameshift frequency. The first 3' nucleotide has the primary effect, with, in order of decreasing efficiency, U > C > A > G. This effect is independent of other stimulators of frameshifting. It is detected with other X XXA AAG sequences, but not with several other heptameric -1 shift sites. Pairing of E. coli tRNALYS with AAG is especially weak at the third codon position. We propose that strong stacking of purines 3' of AAG stabilizes pairing of tRNALys, diminishing the chance of codon:anticodon dissociation that is a prerequisite for the realignment involved in frameshifting.
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PMID:Influence of the stacking potential of the base 3' of tandem shift codons on -1 ribosomal frameshifting used for gene expression. 1187 58

Programmed -1 ribosomal frameshifting, involving tRNA re-pairing from an AAG codon to an AAA codon, has been reported to occur at the sequences CGA AAG and CAA AAG. In this study, using the recoding region of insertion sequence IS3, we have investigated the influence on frameshifting in Escherichia coli of the first codon of this type of motif by changing it to all other NNA codons. Two classes of NNA codons were distinguished, depending on whether they favor or limit frameshifting. Their degree of shiftiness is correlated with wobble propensity, and base 34 modification, of their decoding tRNAs. A more flexible anticodon loop very likely makes the tRNAs with extended wobble more prone to liberate the third codon base, A, for re-pairing of tRNALys in the -1 frame.
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PMID:Programmed translational -1 frameshifting on hexanucleotide motifs and the wobble properties of tRNAs. 1297 Jan 89

We have compared nucleotide substitutions and polymorphisms at codons known to confer drug resistance in subtype B strains of human immunodeficiency virus type 1 (HIV-1) with similar substitutions in viruses of other subtypes. Genotypic analysis was performed on viruses from untreated individuals. Nucleotide and amino acid diversity at resistance sites was compared with a consensus subtype B reference virus. Among patients with non-subtype B infections, polymorphisms relative to subtype B were observed at codon 10 in protease (PR). These included silent substitutions (CTC-->CTT, CTA, TTA) and an amino acid mutation, L10I. Subtype A viruses possessed a V179I substitution in reverse transcriptase (RT). Subtype G viruses were identified by silent substitutions at codon 181 in RT (TAT-->TAC). Similarly, subtype A/G viruses were identified by a substitution at position 67 in RT (GAC-->GAT). Subtype C was distinguished by silent substitutions at codons 106 (GTA-->GTG) and 219 (AAA-->AAG) in RT and codon 48 (GGG-->GGA) in PR. Variations relative to subtype B were seen at RT position 215 (ACC-->ACT) for subtypes A and A/E. These substitutions and polymorphisms reflect different patterns of codon usage among viruses of different subtypes. However, the existence of different subtypes may only rarely affect patterns of drug resistance-associated mutations.
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PMID:Nucleotide and amino acid polymorphisms at drug resistance sites in non-B-subtype variants of human immunodeficiency virus type 1. 1527 11

The natural modification of specific nucleosides in many tRNAs is essential during decoding of mRNA by the ribosome. For example, tRNA(Lys)(UUU) requires the modification N6-threonylcarbamoyladenosine at position 37 (t(6)A37), adjacent and 3' to the anticodon, to bind AAA in the A site of the ribosomal 30S subunit. Moreover, it can only bind both AAA and AAG lysine codons when doubly modified with t(6)A37 and either 5-methylaminomethyluridine or 2-thiouridine at the wobble position (mnm(5)U34 or s(2)U34). Here we report crystal structures of modified tRNA anticodon stem-loops bound to the 30S ribosomal subunit with lysine codons in the A site. These structures allow the rationalization of how modifications in the anticodon loop enable decoding of both lysine codons AAA and AAG.
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PMID:The role of modifications in codon discrimination by tRNA(Lys)UUU. 1557 54

To analyze the relationship of the peripherin gene(PRPH, OMIM17071) mutations with high myopia,genomic DNA was collected from 180 probands with high myopia (<or=-6.0 dipoters) and 60 unrelated persons without high myopia. The coding sequences of PRPH gene in 240 subjects were analyzed using exon-by-exon PCR-heteroduplex-SSCP analysis and sequencing. Variations at codon21TTC-->TTT(Phe21Phe,4/180), nt2138C-->G(IVS3,1/180), codon277 GCC-->ACC(Ala277Thr,8/180), codon237 CCA-->TCA (Arg237stop,1/180), codon292CCG-->CCA (Ala292Ala,1/180),codon361CUG-->CUC(Leu361Leu,12/180), codon369 AAA-->AAG(Lys369Lys,12/180),nt3331G-->C(IVS7,3/180)were detected in a number of probands as indicated in the blanket. Of the 8 variations one( codon 277,G-->A,Ala277Thr) is a missense mutation identified in 8 of the 180patients and one of 60 controls; The mutation of codon361 and codon 369 were synonymous one and linkage each other; Another one(codon237,CCA-->TCA,Arg237stop) is a heterozygous nonsense mutation identified in one patient with autosomal recessive inheritance mode population but not in the 60 normal controls. The others were synonymous mutations. Eight nucleotide variations were found in the PRPH gene. We found no evidence that mutations in the PRPH gene are responsible for the high myopia in Chinese.
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PMID:[Variation of the peripherin gene in Chinese with or without high myopia]. 1613 41

Lysine-accepting transfer RNA from ungerminated and germinated embryo axes of black-eyed peas (Vigna sinensis L. Savi) was fractionated on benzoylated diethylaminoethyl cellulose and reverse phase Freon columns. Cochromatography indicated the presence of two similar lysyl transfer RNA fractions in each tissue. Ribosome binding studies revealed that the larger of the two fractions in each case is specific for the AAG codon, while the smaller one recognizes AAA and AAG. Possible implications of this difference in quantities of isoacceptors in translation of genetic information are discussed.
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PMID:The Coding Properties of Lysine-accepting Transfer Ribonucleic Acids from Black-eyed Peas. 1665 87


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