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Results for “Silent Mutation”

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PubMed2006

Glucose-6-phosphate dehydrogenase variants associated with favism in Thai children.

In a study conducted at Songklanagarind Hospital in the south of Thailand, the subjects were 225 patients (210 boys and 15 girls) with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Favism was found in 3.6% of the G6PD-deficient children. Approximately one half of the G6PD-deficient patients with favism were younger than 2 years. Sudden onset of anemia was found within 1 to 3 days after ingestion of dried fava beans. The classic features of favism, which are pallor, hemoglobinuria, and jaundice, were detected in all cases. To characterize the known G6PD mutations in Thai children, molecular analysis was performed for 8 G6PD-deficient children with favism by a combination of polymerase chain reaction-restriction fragment length polymorphism analysis and amplification refractory mutation system analysis. The G6PD variants in these children were G6PD Kaiping 1388,G-->A; G6PD Mahidol 487,G-->A; G6PD Viangchan 871,G-->A; and uncharacterized mutation with silent mutation 1311,C-->T.

Child↗

PubMedDate not supplied

Mutations of p53 gene in gastric carcinoma in Taiwan.

BACKGROUND: p53 gene mutation and p53 protein accumulation is the most common event in human cancers. The present study was conducted to investigate the occurrence of p53 mutations in patients with gastric carcinoma in Taiwan. MATERIALS AND METHODS: Tumor samples from 36 patients with primary gastric carcinoma undergoing radical gastrectomy were evaluated. The mutational status of the p53 (exons 5 to 8) was screened by polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analysis followed by direct sequencing. These results were compared with p53 protein expression as assessed by immunohistochemical staining. RESULTS: Of all 36 gastric carcinomas, mutations of the p53 gene were found in 7 cases (19.4%). These results from direct sequencing indicated that mutations consisted of five missence mutations, one silent mutation and one mutation within the splice donor site of intron 5. Mutations were found at codon 145 in exon 5 (1 case), intron 5 (1 case), codon 248 in exon 7 (1 case), codon 251 in exon 7 (2 cases), codon 285 in exon 8 (1 case) and codon 287 in exon 8 (1 case). The mutation hot spot at codon 251 in gastric cancer has not been observed previously. Over-expression of p53 oncoprotein was observed in 10 patients (27.8%) immunohistochemically. CONCLUSIONS: p53 gene mutation might contribute to the pathogenesis of human gastric carcinoma. However, the suggestion awaits further investigation for confirmation.

Adenocarcinoma↗

PubMed2005

Association of chondromodulin-II Val58Ile polymorphism with radiographic joint destruction in rheumatoid arthritis.

OBJECTIVE: Chondromodulin-II (ChM-II) is a cartilage-derived protein involved in cartilage and bone repair. A study of Japanese patients with rheumatoid arthritis (RA) implicated an association between a 172G --> A (Val58Ile) polymorphism and radiographic damage. We analyzed ChM-II for polymorphisms and investigated the association with radiographically assessed joint destruction in German patients with RA. Possible interactions with the shared epitope (SE) were examined. METHODS: DNA samples from 204 patients with RA, 81 patients with osteoarthritis, and 116 patients with gout, serving as controls, were sequenced. Radiographic damage was assessed by modified Larsen score. Allele and genotype frequencies between groups were compared by Cochrane-Armitage trend tests. RESULTS: Five missense mutations, one silent mutation, and 5 intronic polymorphisms were found. Allele and genotype frequencies were similar in both disease groups. Larsen scores were significantly higher in RA patients carrying the 172AA (Ile/Ile) genotype (Larsen 96.8), than in RA patients with the 172GA (Val/Ile; Larsen 69.5) or 172GG (Val/Val; Larsen 54.8; p = 0.001) genotypes. Odds ratios to develop more severe radiographic joint damage (Larsen score > 90; above 75th percentile) were 4 and 15.5 for the 172GA and 172AA genotypes, respectively. Presence of a 172A allele increased the risk for enhanced radiographic damage 3-fold. SE and ChM-II 172A alleles emerged as 2 independent risk factors. A potentiated interaction of these risk alleles could not be verified. CONCLUSION: Our data indicate that ChM-II Val58Ile polymorphism is associated with radiographic progression of joint destruction, particularly in German patients with RA negative for SE.

Analysis of Variance↗

PubMed2003

Comparative studies of somatic and ongoing mutations in immunoglobulin heavy-chain variable region genes in diffuse large B-cell lymphomas of the stomach and the small intestine.

CONTEXT: Many diffuse large B-cell lymphomas (DLBCLs) of the stomach are believed to represent high-grade transformation of low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type, which is of memory B-cell origin, displaying evidence for positive antigen selection and a low level of ongoing somatic mutation of the rearranged immunoglobulin heavy-chain variable region (V(H)) genes. The pattern of somatic mutation has been studied little in intestinal DLBCLs. OBJECTIVE: To assess evidence for antigen selection and the levels of ongoing mutation, we analyzed the ratio of replacement to silent mutations, as well as the frequency of intraclonal sequence variation in gastric and small intestinal DLBCLs that showed no concomitant low-grade component. DESIGN: Genomic DNA was extracted from formalin-fixed paraffin blocks of gastric (n = 6) and small intestinal (n = 6) DLBCLs. The complementarity-determining region 2 and framework region 3 sequences (<200 base pairs) of the rearranged immunoglobulin V(H) gene were obtained from polymerase chain reaction-amplified product, and the ratio of replacement-to-silent mutations and the frequency of intraclonal sequence variation were determined. RESULTS: Clustering of replacement mutations in complementarity-determining region 2 with a high (>2.9) ratio of replacement-to-silent mutations was observed in 5 gastric DLBCLs, whereas it was recognized in only 1 intestinal DLBCL. Intraclonal sequence variation was observed in 6 intestinal and 5 gastric DLBCLs. The frequency of ongoing mutation was much higher in the intestinal (median, 0.33%) than in the gastric DLBCLs (median, 0.13%), but the difference was not statistically significant (P =.09). CONCLUSIONS: The mutation pattern was consistent with positive antigen selection in gastric DLBCLs, but not in the intestinal tumors. Ongoing mutation was much more frequent in the intestinal than in the gastric DLBCLs. These findings suggest that positive antigen selection plays a major role in a significant proportion of gastric tumors, whereas germinal center reaction with aberrant mutation is important in small intestinal DLBCLs.

Adult↗

PubMed2005

Gefitinib-sensitive mutations of the epidermal growth factor receptor tyrosine kinase domain in chinese patients with non-small cell lung cancer.

PURPOSE: Studies have shown that mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain are associated with response of lung cancer to gefitinib (Iressa, AstraZeneca Corp., Shanghai, China). A higher incidence of EGFR mutation was observed in non-small cell lung cancer (NSCLC) patients of Japanese origin compared with those of American origin. However, no data about such mutations in Chinese patients with NSCLC could be obtained. METHODS: Primary NSCLC tissues were obtained for analysis of mutations in exons 18 to 21 of EGFR from a total of 76 patients, of whom 54 did not receive gefitinib therapy and 22 did. PCR products were sequenced directly and mutations were confirmed by an independent PCR and sequence analysis. All types of mutation were cloned and sequenced. RESULTS: A total of 10 types of mutation were found in the series of patients, including two different silent mutations in exon 20 from 11 patients. More than half of the silent mutations (6 of 11) in exon 20 coexisted with other mutations. Mutations were more frequent in adenocarcinoma (17 of 35; 48.6%) compared with squamous carcinoma (1 of 19; 5.3%) among untreated patients. Similar mutations were observed in all seven gefitinib-treated patients with partial response, and no mutations were detected in all eight patients with progressive disease (P < 0.001), except two silent mutations. Three mutations were observed in seven patients with stable disease. CONCLUSIONS: Mutations in the epidermal growth factor receptor tyrosine kinase domain in lung adenocarcinomas from Chinese patients were more frequent than reported previously in lung adenocarcinomas from American patients. Such mutations were well correlated with tumor response to gefitinib.

Adenocarcinoma↗

PubMed1999

Variability of the glycoprotein G gene in clinical isolates of herpes simplex virus type 1.

Glycoprotein G (gG) of herpes simplex virus type 1 (HSV-1) has been used as a prototype antigen for HSV-1 type-specific serodiagnosis, but data on the sequence variability of the gene coding for this protein in wild-type strains are lacking. In this study, direct DNA sequencing of the gG-1 genes from PCR products was performed with clinical HSV-1 isolates from 11 subjects as well as with strains Syn 17(+), F, and KOS 321. The reference strains Syn 17(+) and F showed a high degree of conservation, while KOS 321 carried 13 missense mutations and, in addition, 12 silent mutations. Three clinical isolates showed mutations leading to amino acid alterations: one had a mutation of K(122) to N, which is a gG-1-to-gG-2 alteration; another contained all mutations which were observed in KOS 321 except two silent mutations; and the third isolate carried five missense mutations. Two clinical isolates as well as strain KOS 321 showed a mutation (F(111)-->V) within the epitope of a gG-1-reactive monoclonal antibody (MAb). When all viruses were tested for reactivity with the anti-gG-1 MAb, the three strains with the F(111)-->V mutation were found to be unreactive. Furthermore, gG-1 antibodies purified from sera from the two patients carrying strains mutated in this epitope were less reactive when they were tested by an HSV-1-infected-cell assay. Therefore, our finding that the sequence variability of the gG-1 gene also affects B-cell epitope regions of this protein in clinical isolates may have consequences for the use of this protein as a type-specific antigen for serodiagnosis.

Adult↗

PubMed2005

A novel nonsense mutation in the SCN5A gene leads to Brugada syndrome and a silent gene mutation carrier state.

BACKGROUND: Brugada syndrome (BS) is an electrical cardiac disorder with a right bundle branch block and ST segment elevation in leads V1 to V3 on surface electrocardiograms (ECGs), and is a syndrome that may lead to sudden cardiac death. PURPOSE: The aim of the present study was to screen for mutations in the SCN5A gene in a family with BS, and to characterize the consequences of the mutation on channel function. RESULTS: A heterozygous nonsense SCN5A mutation (W822X) was identified in the index patient. The mutation was confirmed in the patient's asymptomatic 16-year-old brother and 48-year-old father. The mutation was absent in the index patient's sister and mother. The ECG of the index patient showed a BS type 2 ECG phenotype, which converted into a type 1 ECG phenotype in the presence of flecainide. The ECG of the patient's brother was not typical for BS, but ajmaline treatment unmasked a type 1 ECG phenotype. The ECG of the asymptomatic father was normal at baseline and in the presence of ajmaline. No Na+ currents could be measured in tsA201 cells transfected with W822X mutant channels. Heterozygote expression showed a nearly 50% reduction in Na+ current amplitude with no significant alterations of biophysical properties, indicating a loss of functional Na+ channels, obviously without any dominant-negative activity on wild type channels. CONCLUSIONS: The haploinsufficiency of the Nav1.5 protein is the plausible explanation for the clinical BS phenotype in this family. Because the heterozygous W822X mutation theoretically leads to channel expression at one-half of the normal level, the authors suggest that a modifier gene may influence or rescue the phenotype in the asymptomatic family members.

Adolescent↗

PubMed1999

Molecular characterization of a porcine enteric calicivirus genetically related to Sapporo-like human caliciviruses.

Porcine enteric calicivirus (PEC) is associated with diarrhea in pigs, and to date it is the only cultivable enteric calicivirus (tissue culture-adapted [TC] PEC/Cowden). Based on sequence analysis of cDNA clones and reverse transcription-PCR products, TC PEC/Cowden has an RNA genome of 7,320 bp, excluding its 3' poly(A)(+) tail. The genome is organized in two open reading frames (ORFs), similar to the organizations of the human Sapporo-like viruses (SLVs) and the lagoviruses. ORF1 encodes the polyprotein that is fused to and contiguous with the capsid protein. ORF2 at the 3' end encodes a small basic protein of 164 amino acids. Among caliciviruses, PEC has the highest amino acid sequence identities in the putative RNA polymerase (66%), 2C helicase (49.6%), 3C-like protease (43.7%), and capsid (39%) regions with the SLVs, indicating that PEC is genetically most closely related to the SLVs. The complete RNA genome of wild-type (WT) PEC/Cowden was also sequenced. Sequence comparisons revealed that the WT and TC PEC/Cowden have 100% nucleotide sequence identities in the 5' terminus, 2C helicase, ORF2, and the 3' nontranslated region. TC PEC/Cowden has one silent mutation in its protease, two amino acid changes and a silent mutation in its RNA polymerase, and five nucleotide substitutions in its capsid that result in one distant and three clustered amino acid changes and a silent mutation. These substitutions may be associated with adaptation of TC PEC/Cowden to cell culture. The cultivable PEC should be a useful model for studies of the pathogenesis, replication, and possible rescue of uncultivable human enteric caliciviruses.

Amino Acid Sequence↗

PubMed1993

p53 gene mutations in gastric adenomas.

p53 gene alterations in ten gastric adenomas and one carcinoma arising in an adenoma were analyzed by deoxynucleotide sequencing. Three (30%) of the ten gastric adenomas had p53 gene mutations, one adenoma showing a frameshift mutation and two others showing silent mutations. In addition, two missense mutations occurred in the carcinoma arising in an adenoma. Histologically, the adenomas containing silent mutations revealed moderate dysplasia. Immunoreactivity to p53 protein was also examined in 61 gastric adenomas, 19 carcinomas arising in adenomas and 48 early well-differentiated adenocarcinomas of the stomach (these included the tumors analyzed by deoxynucleotide sequencing). No staining for p53 was seen in the pure adenomas, but positive immunoreactivity was observed in 27% of the adenocarcinomas and 10.5% of the carcinomas arising in adenomas. These results suggest that p53 gene mutation is an early event in gastric carcinogenesis and missense mutation may play a crucial role in the conversion from adenoma to adenocarcinoma.

Adenoma↗

PubMed2003

High-level expression of porcine liver cytochrome P-450 reductase catalytic domain in Escherichia coli by modulating the predicted local secondary structure of mRNA.

A direct expression system for the solubilized catalytic domains of NADPH-cytochrome P-450 reductase (sCPR) from rat (RsCPR) and porcine (PsCPR) in Escherichia coli cells was constructed using the expression plasmid pCWori(+). PsCPR was minimally expressed, whereas RsCPR was highly expressed. Replacement of the nucleotides encoding Thr(60)Ser(61)Ser(62) in PsCPR with those for Ala(60)Pro(61)Pro(62) in RsCPR markedly increased the expression level of the protein. The local secondary structures of the mRNAs, which were predicted with the prediction program GeneBee (http://www.genebee.msu.su), suggested that the intramolecular double strand between the ribosome binding site (RBS) and the Thr(60)Ser(61)Ser(62) codons in PsCPR, and/or the base-pairing at the initiation codon of the mRNAs significantly affected protein expression. Silent mutations were systematically introduced into the codons for Thr(58) and Thr(60)Ser(61) in PsCPR to modulate the local secondary structure of the mRNA. The expression level of the silently mutated PsCPR suggests that the expression level of PsCPR depends on the stability of the local structure at the RBS in the mRNA. A high-level expression system for wild-type PsCPR was constructed by introducing silent mutations at the codons for Thr(60)Ser(61) in PsCPR. The purified PsCPR showed the characteristic absorption spectral changes of sCPR after reduction with NADPH. The yield of purified PsCPR from 1 liter of culture fluid was 45.8 mg. These results substantiate that the introduction of silent mutations in the section of the gene encoding the N-terminal region of the protein based on the predicted local secondary structure of the mRNA at the RBS is a useful approach to control and increase the expression level of heterologous proteins in E. coli cells.

Amino Acid Sequence↗

PubMed2006

Mutations in the rpoB gene of rifampicin-resistant Mycobacterium tuberculosis strains from Thailand and its evolutionary implication.

Novel mutations in the rpoB gene are reported for 70 rifampicin-resistant (RIFr) M. tuberculosis strains from Thailand. Sequence analysis of these strains revealed mutations in a 435 base-pair region of the rpoB gene. Twenty-eight strains (40%) had single mutations, and 26 of those strains had mutations at positions never before reported, of which, just one had a substitution at Val-432 (Asp), and the remaining 25, a silent mutation at Gln-517. All other strains had multiple mutations, of which 24 (34%) had mutations at two positions; 9(13%), at three positions; 2(3%), at five positions; and 1(1%) at six positions. Five strains (7%), reported to have the RIFr phenotype, contained no mutation in the examined region of the rpoB gene. Surprisingly, one RIFr strain had silent mutations at 29 positions. By far the dominant mutation was the silent mutations at Gln-517 (86%). This investigation demonstrates that mutations in the rpoB gene of M. tuberculosis strains from Thailand are more varied than previously reported for RIFr M. tuberculosis strains. Screening by means of PCR-SSCP clearly separated RIFr strains from rifampicin-susceptible (RIFs) strains. There was no correlation between RIFr mutations and random amplified polymorphic DNA (RAPD) types.

Antibiotics, Antitubercular↗

PubMed1990

Rapid molecular evolution of wild type 3 poliovirus during infection in individual hosts.

A panel of nine neutralizing monoclonal antibodies was used to analyse the antigenic properties of 188 plaque-purified type 3 poliovirus strains from 17 faecal specimens, derived from eight people during a 2 month observation period. Most poliovirus specimens consisted of a mixture of antigenically distinct variants and the composition of the mixture was found to change between sequential specimens in many individuals, indicating antigenic evolution. Thirty-five strains representing different antigenic patterns were selected for partial sequencing of genomic RNA. Mutations leading to amino acid substitutions, as well as silent mutations, were seen at and close to the known antigenic sites. The frequency of silent mutations was used to estimate the evolutionary potential of the virus. The largest difference in silent changes between strains isolated from one person was 0.8%, which corresponds to a minimum of about 60 mutations per genome within a period of 3 weeks. The observed incidence of silent mutations between isolates from different persons was usually between 0.8 and 2%. These figures agree with the previously reported overall mutation rates of poliovirus, determined by other methods.

Amino Acid Sequence↗

PubMed2006

Absence of beta-catenin alteration in hepatic tumors induced by p-nitroanisole in Crj:BDF1 mice.

In the present study, beta-catenin localization in hepatocellular neoplasms and hepatoblastomas, induced by oral administration of p-Nitroanisole (pNA) in Crj:BDF1 for 2 years, was evaluated by immunohistochemistry along with genetic alterations in exon 2 of beta-catenin by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) approach. Genomic DNA was isolated from paraffin sections of a total of 53 liver tumors. Immunohistochemical analysis revealed no abnormal accumulation of the beta-catenin protein in any of the cases. No mutations (0/13), 20% silent mutations (3/15) and 8% silent plus 12% functional mutations (2 + 3/25), not in the multiple phosphorylation sites of beta-catenin, were observed in hepatocellular adenomas, carcinomas and hepatoblastomas, respectively. The results indicate that beta-catenin does not play an important role in development of hepatic tumors induced by pNA in Crj:BDF1 mice.

Animals↗

PubMed1998

[Genetic polymorphism of human CYP2E1: new allels detected in exons and exon-intron junctions].

Cytochrome P450-2E1 (CYP2E1) is a major component of the microsomal ethanol-oxidizing system (MEOS) and is also involved in the metabolism of a variety of foreign compounds including carcinogens. It has been shown that there is an interindividual variation in the expression of human hepatic CYP2E1. Gene-environmental interactions have been suggested to account for the difference. In this study, we screened nine exons of the human CYP2E1 gene for detecting allelic variants in genomic DNA samples obtained from 115 Japanese controls, 96 Japanese alcoholics and 124 American control subjects. A novel missense mutation in exon 2 (V72L) was found in Japanese controls, and another missense mutation in exon 8 (D394G) was detected in American Caucasians. In addition, two novel silent mutations in exon 6 (T303T) and exon 8 (F420F) were found in Japanese controls and alcoholics. Especially the silent mutation in exon 8 was highly polymorphic among three population groups. The mutation in exon 2 (V72L) was detected only in Japanese controls, but not in alcoholics although it shows no significant difference. Gene frequency of the silent mutation in exon 8 was significantly higher in Japanese than American Caucasians (34.8% vs 21.0%, p < 0.02). Our data indicated that nucleotide replacement in the open reading frame is no major factor responsible for alcoholism. However, functional significance of the two novel missense mutations remains to be detailed.

Alcoholism↗

PubMed2001

Codon 325 sequence polymorphism of the estrogen receptor alpha gene and bone mineral density in postmenopausal women.

Estrogen receptor alpha (ER alpha) encoding gene is one of the candidate genes to be involved in the development of osteoporosis. Until now correlation between three ER gene polymorphisms (identified with PvuII, XbaI and BstUI) and bone mineral density (BMD) have been investigated. The results of these studies are contradictory. Thus the aim of our work was to search for new, yet unknown, and probably more informative polymorphism(s) of the ER alpha gene. For detection of mutations the whole coding region of the ER alpha gene was screened systematically. In a group of 85 late postmenopausal women all of the eight exons were amplified by polymerase chain reaction (PCR) and fragments were further analyzed by single-stranded conformation polymorphism (SSCP) analysis. Mutations were confirmed by direct DNA sequencing. In the whole coding region of the ER alpha gene two silent mutations in codon 87 and 325, respectively, were found. The silent mutation in codon 85 of exon 1 (GCG-->GCC; A87A) was described previously, as BstUI polymorphism. On the other side, the silent mutation in codon 325 (CCC-->CCG; P325P), located in exon 4, has not been analyzed so far in correlation with BMD. According to the distribution of genotypes CC:CG:GG=49.4:41.2:9.4, we can affirm the existence of genetic polymorphism in codon 325 in our population of late postmenopausal women. The mean femoral neck BMD, but not the lumbar spine BMD, was significantly lower (P=0.029) in the homozygous GG-women with CCG/CCG codon 325 as compared to the homozygous CC-women with the normal codon CCC/CCC. Our results suggest that codon 325 sequence polymorphism of the ER alpha gene might be one of the factors associated with low femoral neck BMD.

Aged↗

PubMed2005

Caprine kappa-casein (CSN3) polymorphism: new developments in molecular knowledge.

A high degree of polymorphism was recently found at the kappa-casein (CSN3) locus in the domesticated goat (Capra hircus). In the present study, 2 new patterns previously identified by PCR-single-strand conformation polymorphism analysis (SSCP) were characterized. The allele provisionally named "X" (GenBank Accession no. AY350425) differs from CSN3*C (AF485341) by a (silent) A-->G substitution at position 509 of the goat CSN3 reference sequence (X60763). As this newly identified sequence changes the amino acid sequence, and the already known CSN3*C allele (AF485341) has an additional silent mutation, we proposed a change in nomenclature to reflect these changes, indicating the silent mutation with the prime symbol (i.e.,'). The CSN3*M allele (provisionally named "Y") results in a new protein variant, differing by 2 nonsynonymous mutations from the CSN3*F allele. The new variant is characterized by a G-->A transition at nucleotide position 384, resulting in the amino acid exchange Asp90-->Asn90, and a C-->T transition at position 550, resulting in a Val145-->Ala145 substitution. Thus, the number of alleles identified in the domesticated goat has increased to 16, of which 13 are protein variants and 3 are silent mutations, involving a total of 15 polymorphic sites in CSN3 exon 4. Data on the distribution of the main alleles in 7 goat breeds of Europe, West Africa, and the Near East show differences in the occurrence and frequency of the alleles between breeds and geographic origin with the highest number of alleles found in goat breeds from the Near East.

Alleles↗

PubMed1998

Delineation of selective influences shaping the mutated expressed human Ig heavy chain repertoire.

After Ag exposure, somatic hypermutation and subsequent selection play significant roles in shaping the peripheral B cell repertoire. However, the disparate impact of each process has not been completely delineated. To address this, the mutational patterns of a large panel of productive V(H)DJ(H) rearrangements of individual human B cells were analyzed and compared with those of a previously reported panel of nonproductive V(H)DJ(H) rearrangements. The productive V(H) rearrangements exhibited a significantly lower mutational frequency and a significantly smaller number of replacement mutations than the nonproductively rearranged genes, suggesting that structural constraints of the Ig molecule and selective influences both impacted the repertoire, militating against replacement mutations. Positive selection favored a mean of four to six replacements in complementarity-determining region 1 (CDR1) and CDR2, and less than two replacements in the framework regions (FRs). In contrast, the negative impact of replacement mutations generated an increased number of silent mutations within both the CDRs and FRs of the productive repertoire accompanied by a net increase in the ratio of replacement to silent mutations in the CDRs compared with that in the FRs. Moreover, there was a negative influence on the distribution of amino acid changes resulting from mutations of highly mutable codons, such as AGY, TAY, GTA, and GCT, preferentially leading to conservative changes in the expressed Ig repertoire. The results are consistent with the conclusion that the expressed repertoire is limited, compared with the potential generated by the mutational machinery, by the dual requirements of avoiding autoreactivity and satisfying structural constraints of an intact Ig molecule.

Codon↗

PubMed2004

[Studies on the nucleotides sequences of extended-spectrum-beta-lactamases encoding genes of Escherichia coli and Klebsiella pneumoniae and the related molecular evolution].

OBJECTIVE: To identify TEM-type and SHV-type ESBLs encoding genes of ESBLs-producing Klebsiella pneumoniae and Escherichia coli isolated from clinical species in West China Hospital of Sichuan University and study the molecular evolution of the ESBLs. METHODS: The nucleotide sequences of TEM-type and SHV-type ESBLs encoding genes amplified by PCR were detected by automatic sequencer, and the subtypes of the encoding genes were determined by Blastx searching. The molecular evolution of ESBLs was studied by means of bioinformatics. RESULTS: In this study, the subtypes of ESBLs were SHV-2 and TEM-19, the distribution of silent mutation in ten bla(SHV-2) was identical, and that of two bla(TEM-19) was the same; the distribution of silent mutation of bla(TEM-19) was the same as that of bla(TEM-1). The distribution of silent mutation of bla(SHV-2) observed here was different from that observed in other countries. CONCLUSION: SHV-2 was the main ESBLs in this study. The bla(SHV-2) and bla(TEM-19) in this study originated from the same transferable variants respectively. The prevalent SHV-2 in different countries resulted from convergent evolution. It seems possible that the bla(TEM-19) identified by this study might originate directly from the transferable bla(TEM-1) identified in this study.

DNA, Bacterial↗