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At least 217 records · Page 12Linked to original sources
PubMed2001

Linkage between bronchial responsiveness to methacholine and gene markers of IL-4 cytokine gene cluster and T-cell receptor alpha/delta gene complex in Korean nuclear families.

BACKGROUND: Several candidate genes have been reported to be linked to intermediate phenotypes of asthma in Caucasian populations. OBJECTIVE: To evaluate linkage between phenotypes of asthma and gene markers of high affinity IgE receptor-beta gene (D11S97), IL-4 cytokine gene cluster (IL-4R1), and T-cell receptor alpha/delta gene complex (D14S50) in Korean nuclear families. METHODS: Nuclear families (127 probands and their 130 siblings) for the linkage analysis were ascertained through asthmatic children. Linkages between total serum IgE response, skin responses to common aeroallergens, and bronchial responsiveness to methacholine were performed using a sib-pair approach. RESULTS: The square difference of the slope of the dose-response curve (DRS) between sib-pairs with two IL-4R1 identical alleles was smaller than with one or with neither IL-4R1 identical allele (P = 0.004). As for D14S50, the differences of DRS between sib-pairs with two identical alleles and with one identical allele were smaller than with neither identical alleles (P = 0.01). As for D11S97, no significant differences were observed among the groups with identical alleles of two, one or zero. With regard to total serum IgE levels, no significant linkage was found between this phenotype and the above three gene markers. As for skin responses to common aeroallergens, significant evidence was obtained to establish a linkage between this phenotype and the marker IL-4R1 (P = 0.01). However, no significant linkage was found between this phenotype and the markers D11S97 and D14S50. CONCLUSION: The expression of bronchial responsiveness to methacholine may be influenced by genetic factors in the IL-4 cytokine gene cluster and/or T-cell receptor alpha/delta gene complex, but the genetic influence of the FcepsilonRI-beta gene may be minimal in the expression of bronchial responsiveness in Korean nuclear families.

Adolescent↗
PubMed1995

[Genes, behavior and disease. A sceptic's view of gene mapping and gene therapy].

This paper contains four parts. The first focuses on The Human Genome Project (HGP). The concept of a "normal sequence" seems problematic. The second part reviews what is meant by "genetically-caused" and by "a (several) gene(s) for a trait". Genes work in concert, and it is likely that many genes together influence most complex traits. A difference in traits between two individuals, however, can be due to a difference in a single gene, as is the case for several thousand rare "genetic diseases". Such diseases were the original focus of gene therapy. Could gene therapy also be applied to more common complex traits? Diagnostic problems and the unsuccessful attempts to find a single gene difference in patients with manic depressive disorder, schizophrenia and Alzheimer's disease are discussed. Part three reviews future genetic research into complex traits and what kind of treatment can realistically be expected. It is concluded that improved diagnostics is the most likely outcome, not therapy. Part four raises arguments from the emerging Darwinian approach to medicine and states that it is far too early to even think of gene therapy. The needed knowledge about genes, behaviour and disease will not come from the one-sided genetic effort represented by HGP, and the resources should instead be invested in several different approaches to these complex issues.

Behavior↗
PubMed1993

The genes of major lysosomal membrane glycoproteins, lamp-1 and lamp-2. 5'-flanking sequence of lamp-2 gene and comparison of exon organization in two genes.

Human lysosomal membrane glycoproteins lamp-1 and lamp-2 are the major sialoglycoproteins present in lysosomal membranes. The expression of lamp-2 molecules is uniquely regulated, whereas lamp-1 is constitutively synthesized. In order to investigate the unique expression of lamp-2, and the gene evolution of lamp-1 and lamp-2, we isolated genomic phage clones encoding these glycoproteins. Comparison of the genomic and cDNA sequences revealed that the lamp-2 gene consists of nine exons. The transcriptional start site of the lamp-2 gene was determined by primer extension analysis. In order to locate the transcriptional regulatory region of this gene, various regions of 5'-sequences were tested for promoter activity using chloramphenicol acetyltransferase as a reporter molecule. The results revealed that the 5'-flanking sequence from -172 to -20 base pairs has strong promoter activity. In this sequence, potential SP1 and AP-1 binding sites and CAAT boxes are found. Most notably, the promoter activity is suppressed if the 5' farther upstream KpnI repeat sequence is included in the tested 5'-flanking sequence, thus suggesting that the KpnI repeat sequence may have some regulatory function in the lamp-2 gene expression. Comparison of the exon organization of human lamp-2 and lamp-1 genes, or chicken lamp-1 gene, reveals that these two proteins utilize the same exon phase in corresponding introns. Furthermore, each exon encodes almost identical portions of the proteins. On the other hand, the amino acid sequence of human lamp-1 is more homologous to lamp-1 of other species than it is to human lamp-2. These results indicate that lamp-1 and lamp-2 genes were most likely produced by duplication of a primordial gene, which took place early in evolution.

Amino Acid Sequence↗
PubMed2004

Presence of a bacterial-like citrate synthase gene in Tetrahymena thermophila: recent lateral gene transfers (LGT) or multiple gene losses subsequent to a single ancient LGT?

Citrate synthase is the initial enzyme in the tricarboxylic acid cycle of mitochondria. In plants and fungi, it is the second isozyme in the glyoxylate cycle of peroxisomes (or glyoxysomes), and it is also present in bacteria. Some of the biochemical reactions in the glyoxylate cycle of the ciliated protozoan Tetrahymena pyriformis depend upon mitochondrial enzymes, as T. pyriformis lacks some glyoxysome-specific enzymes. Here we demonstrate a new citrate synthase gene from Tetrahymena thermophila that is different from the mitochondrial counterpart. A potential peroxysome-targeted signal was detected in the N-terminus, suggesting the localization of the enzyme in peroxysomes. Phylogenetic analysis placed the Tetrahymena sequence in a clade consisting of a few sequences from eukaryotes such as cellular slime molds and two land plants, near a green sulfur bacterium and many proteobacteria as a sister group but not in a mitochondrial clade. Southern blot analysis revealed that this type of gene was absent from distantly related ciliates and other species of Tetrahymena except for the closest species, T. mallaccensis. The scattered presence of the bacterial-like genes among distantly related eukaryotes suggests three alternative interpretations of acquisition of the novel glyoxysomal citrate synthase gene via lateral gene transfer (LGT). (1). Some eukaryotes independently acquired the gene from a common bacterium or closely related bacteria via LGT. (2). A hypothetical eukaryote once acquired the gene, which was thereafter independently transferred from the eukaryote to other eukaryotes. (3). A single event of LGT (or duplication) occurred in a certain common ancestor of eukaryotes, followed by multiple losses in many eukaryotic lineages during the subsequent evolution. Considering the monophyly of the bacterial-like eukaryotic citrate synthase genes, the first model is somewhat unlikely, even though it is not impossible. The second and third models can rationally explain the present observation, so these models are discussed in some detail.

Amino Acid Motifs↗
PubMed1984

env-Related leukemogenic genes (gp55 genes) of two closely related polycythemic strains of Friend spleen focus-forming virus possess different recombination points with an endogenous mink cell focus-forming virus env gene.

The unintegrated circular provival DNA of the replication-competent, helper Friend murine leukemia virus (F-MuLV) in a polycythemic strain of Friend leukemia virus complex (FLV, K-1 strain) was molecularly cloned after insertion into the EcoRI site of the plasmid pBR322. The nucleotide sequence of its env gene has been determined. Sequences of this F-MuLV env gene, and the previously reported env-related gene (gp55 gene) of Friend spleen focus-forming virus (SFFV) (K-1 strain) were compared to that of the same gene of the other polycythemic SFFV isolate, SFFV (502), recently reported by Clark and Mak. The gp55 genes of the two SFFV isolates are almost identical to each other and have several common characteristic structures. However, the two gp55 genes are different in that the gp55 gene of SFFV (K-1) has a longer nonecotropic MuLV env sequence than that of SFFV (502). This finding may suggest that each SFFV isolate has been generated independently by recombination between a putative defective variant of F-MuLV and an endogenous mink cell focus-forming virus env sequence.

Amino Acid Sequence↗
PubMed1986

Gene within a gene: nested Drosophila genes encode unrelated proteins on opposite DNA strands.

A pupal cuticle protein gene has been found within an intron of a Drosophila gene that encodes three purine pathway enzymatic activities. The intronic gene is encoded on the DNA strand opposite the purine pathway gene and is itself interrupted by an intron. Whereas the purine pathway gene is active throughout development, the intronic cuticle protein gene is expressed primarily over a 3 hr period in the abdominal epidermal cells of prepupae that secrete the pupal cuticle. Therefore, a housekeeping gene and a developmentally regulated gene function in a nested arrangement.

Acyltransferases↗
PubMed1996

A sequence analysis of von Willebrand factor mRNA, gene, and pseudogene in two patients with von Willebrand disease type 2B, and an investigation of gene conversion in its gene.

We identified the point mutations in two unrelated patients with von Willebrand disease (vWD) type 2B using sequence analyses of the gene, pseudogene and messenger RNA of vWF. Both patients were determined to be heterozygotes with amino acid transitions of 1308 Arg-->Cys in Case 1 and 1316 Val-->Met in Case 2. Moreover, we also found single base transitions 7541 A-->G in intron 27 of the active gene, and 7642 A-->G, which thus destroyed the Kpn 1 site, in its pseudogene in both cases. Since these mutations represented changes in the base between the gene and its pseudogene, we studied the presence of gene conversion in exon 28 of vWF gene to clarify its pathological role. Using RT-PCR and an allele-specific restriction enzyme analysis, we identified no gene conversions in this region in four other patients with vWD, 25 normal subjects and one cell line, MEG01. Based on these findings, gene conversion in the vWF gene is not considered to be a frequent phenomenon in either vWD patients or normal subjects.

Adult↗
PubMed1997

A rare type of overlapping genes in bacteriophage T4: gene 30.3' is completely embedded within gene 30.3 by one position downstream.

We have previously proposed the existence of one of the rarest types of overlapping genes in bacteriophage T4. We now present the results demonstrating that in a pair of T4 overlapping genes, 30.3 and 30.3', the smaller gene, 30.3', is entirely enclosed within the other by one position downstream. We have constructed plasmids in which different open reading frames from the gene 30.3 region were fused with the 5' end of the lacZ beta-galactosidase (betaGal) gene of Escherichia coli. The gene fusions have been obtained at the position of a HindIII site which was introduced just upstream from the stop codon of gene 30.3'. High betaGal activities have been estimated in the case of plasmids carrying 30.3::lacZ and 30.3'::lacZ fusions. The apparent molecular weights of the fusion proteins, the determined N-terminal sequences, as well as the detected betaGal activities, confirm the structure and arrangement of out-of-phase overlapping genes 30.3 and 30.3'.

Bacteriophage T4↗
PubMed1992

A functional promoter shift of a chloroplast gene: a transcriptional fusion between a novel psbA gene copy and the trnK (UUU) gene in Pinus contorta.

A comparative transcription analysis of the chloroplast trnK-psbA-trnH region of the two pine species Pinus contorta and Pinus sylvestris is reported. The chloroplast genome of P. contorta has previously been shown to contain a duplicated psbA gene copy integrated closely upstream of the split trnK gene. This rearrangement has resulted in the gene order psbAI-trnK-psbAII-trnH, where psbAII is the ancestral psbA gene copy. In P. sylvestris, a species which lacks the psbA duplication, transcription of the trnK gene originates from a position 291 bp upstream of the trnK 5' exon, adjacent to a canonical promoter structure. In P. contorta, the corresponding promoter structure has been separated from the trnK gene by the insertion of psbAI, and has, in addition, been partially deleted. Analysis of the transcriptional organization of the trnK-psbA-trnH region of the two pine species revealed that the trnK gene in P. contorta is transcriptionally fused to the inserted psbAI gene copy. As a result, trnK is under the control of the psbA promoter in this species and has therefore acquired psbA-like expression characteristics. In P. sylvestris, accumulation of trnK transcripts is not significantly higher in light-grown than in dark-grown seedlings. In contrast, the level of trnK transcripts in P. contorta is approximately 12-fold higher in the light than in the dark. When light-grown seedlings of the two pine species were compared, an approximately 20-fold higher level of trnK RNAs was found in P. contorta. In both pine species, evidence was obtained for trnK-psbA and psbA-trnH co-transcription.

Bacterial Proteins↗
PubMed2006

Origins and evolution of the recA/RAD51 gene family: evidence for ancient gene duplication and endosymbiotic gene transfer.

The bacterial recA gene and its eukaryotic homolog RAD51 are important for DNA repair, homologous recombination, and genome stability. Members of the recA/RAD51 family have functions that have differentiated during evolution. However, the evolutionary history and relationships of these members remains unclear. Homolog searches in prokaryotes and eukaryotes indicated that most eubacteria contain only one recA. However, many archaeal species have two recA/RAD51 homologs (RADA and RADB), and eukaryotes possess multiple members (RAD51, RAD51B, RAD51C, RAD51D, DMC1, XRCC2, XRCC3, and recA). Phylogenetic analyses indicated that the recA/RAD51 family can be divided into three subfamilies: (i) RADalpha, with highly conserved functions; (ii) RADbeta, with relatively divergent functions; and (iii) recA, functioning in eubacteria and eukaryotic organelles. The RADalpha and RADbeta subfamilies each contain archaeal and eukaryotic members, suggesting that a gene duplication occurred before the archaea/eukaryote split. In the RADalpha subfamily, eukaryotic RAD51 and DMC1 genes formed two separate monophyletic groups when archaeal RADA genes were used as an outgroup. This result suggests that another duplication event occurred in the early stage of eukaryotic evolution, producing the DMC1 clade with meiosis-specific genes. The RADbeta subfamily has a basal archaeal clade and five eukaryotic clades, suggesting that four eukaryotic duplication events occurred before animals and plants diverged. The eukaryotic recA genes were detected in plants and protists and showed strikingly high levels of sequence similarity to recA genes from proteobacteria or cyanobacteria. These results suggest that endosymbiotic transfer of recA genes occurred from mitochondria and chloroplasts to nuclear genomes of ancestral eukaryotes.

Animals↗
PubMed1991

Definition of a GC-rich motif as regulatory sequence of the human IL-3 gene: coordinate regulation of the IL-3 gene by CLE2/GC box of the GM-CSF gene in T cell activation.

The human IL-3 gene, located on chromosome 5, contains several cis-acting DNA sequences, i.e. CLE (conserved lymphokine element) and a GC-rich region, similar to the GM-CSF gene. To investigate the role of these elements, the 5' flanking region of the IL-3 gene was attached to a bacterial chloramphenicol acetyltransferase (CAT) gene. The fusion plasmids were analyzed by an in vitro transcription system using Jurkat cell nuclear extract prepared from cells stimulated with phorbol-12-myristate-13-acetate and calcium ionophore (PMA/A23187), introduced into Jurkat cells, expressed transiently, and stimulated by co-transfection of human T cell leukemia virus type I (HTLV-I) encoded transactivator, p40tax. The GC-rich region enhanced TATA-dependent transcription in the in vitro transcription system and also strongly responded to p40tax stimulation in the in vivo cotransfection assay. Using this GC-rich region as a probe, we identified a constitutive DNA-protein complex, alpha, whose binding specificity correlates with transcription activity. However, this element is not sufficient for the expression of the IL-3 gene in response to T cell activation signals (PMA/A23187) and no sequence was found within the IL-3 gene which mediates the response to PMA/A23187. The enhancer sequence which responds to T cell activation signals may be located outside the IL-3 gene and may be shared by other lymphokines, possibly by GM-CSF. We propose that the GM-CSF enhancer (CLE2/GC box) which mediates the response to T cell activation signals may stimulate the expression of the IL-3 gene.

Base Composition↗
PubMed1990

Genes, variant genes, and pseudogenes of the human tRNA(Val) gene family are differentially expressed in HeLa cells and in human placenta.

Pre-tRNAs(Val) were identified in unfractionated tRNA preparations from HeLa cells and human placenta and their 5' leader structures were deduced from the nucleotide sequences of the corresponding cDNAs. Several of these precursors can be assigned to nine out of the eleven members of the human tRNA(Val) gene family characterized so far, which demonstrates that these gene loci are actively transcribed in vivo. Among the expressed genes there are (a) genes for the two known tRNA(Val) isoacceptor species from human placenta, (b) gene variants that exhibit sequence alterations as compared to conventional genes, and (c) pseudogenes that produce processing-deficient precursors which are not matured to tRNAs. The transcription products of several yet unknown tRNA(Val) genes have also been detected. Furthermore, different expression patterns are observed in the two cell types studied. These data allow for the first time an insight into the in vivo expression of a human tRNA gene family.

Base Sequence↗
PubMed1991

Cloning and characterization of the rad4 gene of Schizosaccharomyces pombe; a gene showing short regions of sequence similarity to the human XRCC1 gene.

The rad4.116 mutant of the fission yeast Schizosaccharomyces pombe is temperature-sensitive for growth, as well as being sensitive to the killing actions of both ultraviolet light and ionizing radiation. We have cloned the rad4 gene by complementation of the temperature sensitive phenotype of the rad4.116 mutant with a S. pombe gene bank. The rad4 gene fully complemented the UV sensitivity of the rad4.116 mutant. The gene is predicted to encode a protein of 579 amino acids with a basic tail, a possible zinc finger and a nuclear location signal. The amino terminal part of the predicted rad4 ORF contains two short regions of similarity to the C-terminal part of the human XRCC1 gene. Codon usage suggests that the gene is very poorly expressed, and this was confirmed by RNA studies. Gene disruption showed that the rad4 gene was essential for the mitotic growth of S. pombe.

Base Sequence↗
PubMed1990

The rpoN gene product of Pseudomonas aeruginosa is required for expression of diverse genes, including the flagellin gene.

The product of the rpoN gene is an alternative sigma factor of RNA polymerase which is required for transcription of a number of genes in members of the family Enterobacteriaceae, including those that specify enzymes of nitrogen assimilation, amino acid uptake, and degradation of a variety of organic molecules. We have previously shown that transcription of the pilin gene of Pseudomonas aeruginosa also requires RpoN (K. S. Ishimoto and S. Lory, Proc. Natl. Acad. Sci. USA 86:1954-1957, 1989) and have undertaken a more extensive survey of genes under RpoN control. Strains of P. aeruginosa that carry an insertionally inactivated rpoN gene were constructed and shown to be nonmotile because of the inability of these mutants to synthesize flagellin. The mutation in rpoN had no effect on expression of extracellular polypeptides, outer membrane proteins, and the alginate capsule. However, the rpoN mutants were glutamine auxotrophs and were defective in glutamine synthetase, indicating defects in nitrogen assimilation. In addition, the P. aeruginosa rpoN mutants were defective in urease activity. These findings indicate that the sigma factor encoded by the rpoN gene is used by P. aeruginosa for transcription of a diverse set of genes that specify biosynthetic enzymes, degradative enzymes, and surface components. These rpoN-controlled genes include pili and flagella which are required for full virulence of the organism.

Bacterial Outer Membrane Proteins↗
PubMed1996

The Bradyrhizobium japonicum rpoH1 gene encoding a sigma 32-like protein is part of a unique heat shock gene cluster together with groESL1 and three small heat shock genes.

The heat shock response of Bradyrhizobium japonicum is controlled by a complex network involving two known regulatory systems. While some heat shock genes are controlled by a highly conserved inverted-repeat structure (CIRCE), others depend on a sigma 32-type heat shock sigma factor. Using Western blot (immunoblot) analysis, we confirmed the presence of a sigma 32-like protein in B. japonicum and defined its induction pattern after heat shock. A B. japonicum rpoH-like gene (rpoH1) was cloned by complementation of an Escherichia coli strain lacking sigma 32. A knockout mutation in rpoH1 did not abolish sigma 32 production in B. japonicum, and the rpoH1 mutant showed the wild-type growth phenotype, suggesting the presence of multiple rpoH homologs in this bacterium. Further characterization of the rpoH1 gene region revealed that the rpoH1 gene is located in a heat shock gene cluster together with the previously characterized groESL1 operon and three genes encoding small heat shock proteins in the following arrangement: groES1, groEL1, hspA, rpoH1, hspB, and hspC. Three heat-inducible promoters are responsible for transcription of the six genes as three bicistronic operons. A sigma 32-dependent promoter has previously been described upstream of the groESL1 operon. Although the hspA-rpoH1 and hspBC operons were clearly heat inducible, they were preceded by sigma 70-like promoters. Interestingly, a stretch of about 100 bp between the transcription start site and the start codon of the first gene in each of these two operons was nearly identical, making it a candidate for a regulatory element potentially allowing heat shock induction of sigma 70-dependent promoters.

Amino Acid Sequence↗
PubMed1996

Novel retroviral vector transferring a suicide gene and a selectable marker gene with enhanced gene expression by using a tetracycline-responsive expression system.

A retroviral vector for the enhanced expression of the herpes simplex virus thymidine kinase (HSV tk) gene was developed by using a tetracycline-responsive expression system (TRES). The two components of the TRES, the chimeric transactivator (tTA) and the corresponding tTA-binding cis element (tetO), were both incorporated into a retroviral vector and resulted in high levels of tk gene expression from tetO in target cells. Amphotropic virus supernatants from stable producer cells, generated by the retroviral vector containing the TRES, gave titers of 10(4) to 10(5) G418-resistant CFU/ml on murine NIH 3T3 cells. The retroviral vector (G1tTA-[tetOTkINa]R), in which tetO was used in the opposite orientation relative to viral transcription, was capable of transducing tk and neo genes into murine NIH 3T3 cells to yield a high level of tk gene expression. TK enzyme activity in NIH 3T3 cells transduced by this vector was 417-fold higher than in control cells. This increased TK activity was returned to basal levels in the presence of tetracycline. The level of tk gene expression driven by tetO from G1tTA-[tetOTkINa]R vector in NIH 3T3 cells was fourfold higher at both the mRNA level and the TK enzyme level than that produced by the long terminal repeat of G1Tk1SvNa, the vector being used in the ongoing brain tumor gene therapy trial. Retroviral vectors containing the TRES may be useful therefore in achieving higher levels of tk gene expression, which should facilitate gene therapy approaches in the treatment of cancer.

3T3 Cells↗
PubMed1999

A systematic analysis of 40 random genes in cultured vascular smooth muscle subtypes reveals a heterogeneity of gene expression and identifies the tight junction gene zonula occludens 2 as a marker of epithelioid "pup" smooth muscle cells and a participant in carotid neointimal formation.

An accumulation of evidence suggests that vascular smooth muscle is composed of cell subpopulations with distinct patterns of gene expression. Much of this evidence has come from serendipitous discoveries of genes marking phenotypically distinct aortic cultures derived from 12-day-old and 3-month-old rats. To identify more systematic differences, we isolated 40 genes at random from libraries of these 2 cultures and examined message expression patterns. To determine consistency of differential expression, we measured mRNA levels in 4 sets of cultures in 6 phenotypically distinct aortic cell clones and in balloon injured rat carotid arteries to determine the relevance of these differences in vitro to in vivo biology. The following 5 consistently differentially expressed genes were identified in vitro: zonula occludens 2 (ZO-2); peroxisome proliferator-activated receptor delta (PPARdelta); secreted protein, acidic and rich in cysteine (SPARC); alpha1(I)collagen; and A2, an uncharacterized gene. We examined these 5 clones during carotid artery injury and an inconsistently differentially expressed clone Krox-24 because, as an early response transcription factor, it could be involved in the injury response. PPARdelta, A2, and Krox-24 mRNAs were upregulated during the day after injury. ZO-2 and alpha1(I)collagen messages were modulated for up to a month, whereas SPARC message showed no consistent change. An analysis of ZO-2 and other tight junction genes indicates that tight junctions may play a role in smooth muscle biology. These data suggest that a systematic analysis of these libraries is likely to identify a very large number of differentially expressed genes. ZO-2 is particularly intriguing both because of this tight junction gene's pattern of prolonged over-expression after injury and because of its potential role in determining the distinctive epithelioid phenotype of smooth muscle cells identified in rat and other species.

Age Factors↗
PubMed2002

Persistence and expression of the adenosine deaminase gene for 12 years and immune reaction to gene transfer components: long-term results of the first clinical gene therapy trial.

The first human gene therapy experiment begun in September 1990 used a retroviral vector containing the human adenosine deaminase (ADA) cDNA to transduce mature peripheral blood lymphocytes from patients with ADA deficiency, an inherited disorder of immunity. Two patients who had been treated with intramuscular injections of pegylated bovine ADA (PEG-ADA) for 2 to 4 years were enrolled in this trial and each received a total of approximately 10(11) cells in 11 or 12 infusions over a period of about 2 years. No adverse events were observed. During and after treatment, the patients continued to receive PEG-ADA, although at a reduced dose. Ten years after the last cell infusion, approximately 20% of the first patient's lymphocytes still carry and express the retroviral gene, indicating that the effects of gene transfer can be remarkably long lasting. On the contrary, the persistence of gene-marked cells is very low (< 0.1%), and no expression of the transgene is detectable in lymphocytes from the second patient who developed persisting antibodies to components of the gene transfer system. Data collected from these original patients have provided novel information about the longevity of T lymphocytes in humans and persistence of gene expression in vivo from vectors driven by the Moloney murine leukemia virus long-terminal repeat (LTR) promoter. This long-term follow-up has also provided unique evidence supporting the safety of retroviral-mediated gene transfer and illustrates clear examples of both the potential and the pitfalls of gene therapy in humans.

Adenosine Deaminase↗