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At least 883 records · Page 49Linked to original sources
PubMed2002

The human L-threonine 3-dehydrogenase gene is an expressed pseudogene.

BACKGROUND: L-threonine is an indispensable amino acid. One of the major L-threonine degradation pathways is the conversion of L-threonine via 2-amino-3-ketobutyrate to glycine. L-threonine dehydrogenase (EC 1.1.1.103) is the first enzyme in the pathway and catalyses the reaction: L-threonine + NAD+ = 2-amino-3-ketobutyrate + NADH. The murine and porcine L-threonine dehydrogenase genes (TDH) have been identified previously, but the human gene has not been identified. RESULTS: The human TDH gene is located at 8p23-22 and has 8 exons spanning 10 kb that would have been expected to encode a 369 residue ORF. However, 2 cDNA TDH transcripts encode truncated proteins of 157 and 230 residues. These truncated proteins are the result of 3 mutations within the gene. There is a SNP, A to G, present in the genomic DNA sequence of some individuals which results in the loss of the acceptor splice site preceding exon 4. The acceptor splice site preceding exon 6 was lost in all 23 individuals genotyped and there is an in-frame stop codon in exon 6 (CGA to TGA) resulting in arginine-214 being replaced by a stop codon. These truncated proteins would be non-functional since they have lost part of the NAD+ binding motif and the COOH terminal domain that is thought to be involved in binding L-threonine. TDH mRNA was present in all tissues examined. CONCLUSIONS: The human L-threonine 3-dehydrogenase gene is an expressed pseudogene having lost the splice acceptor site preceding exon 6 and codon arginine-214 (CGA) is mutated to a stop codon (TGA).

Alcohol Oxidoreductases↗
PubMed2005

Mice have a transcribed L-threonine aldolase/GLY1 gene, but the human GLY1 gene is a non-processed pseudogene.

BACKGROUND: There are three pathways of L-threonine catabolism. The enzyme L-threonine aldolase (TA) has been shown to catalyse the conversion of L-threonine to yield glycine and acetaldehyde in bacteria, fungi and plants. Low levels of TA enzymatic activity have been found in vertebrates. It has been suggested that any detectable activity is due to serine hydroxymethyltransferase and that mammals lack a genuine threonine aldolase. RESULTS: The 7-exon murine L-threonine aldolase gene (GLY1) is located on chromosome 11, spanning 5.6 kb. The cDNA encodes a 400-residue protein. The protein has 81% similarity with the bacterium Thermotoga maritima TA. Almost all known functional residues are conserved between the two proteins including Lys242 that forms a Schiff-base with the cofactor, pyridoxal-5'-phosphate. The human TA gene is located at 17q25. It contains two single nucleotide deletions, in exons 4 and 7, which cause frame-shifts and a premature in-frame stop codon towards the carboxy-terminal. Expression of human TA mRNA was undetectable by RT-PCR. In mice, TA mRNA was found at low levels in a range of adult tissues, being highest in prostate, heart and liver. In contrast, serine/threonine dehydratase, another enzyme that catabolises L-threonine, is expressed very highly only in the liver. Serine dehydratase-like 1, also was most abundant in the liver. In whole mouse embryos TA mRNA expression was low prior to E-15 increasing more than four-fold by E-17. CONCLUSION: Mice, the western-clawed frog and the zebrafish have transcribed threonine aldolase/GLY1 genes, but the human homolog is a non-transcribed pseudogene. Serine dehydratase-like 1 is a putative L-threonine catabolising enzyme.

Amino Acid Sequence↗
PubMed2001

Use of molecular beacons to verify that the serine hydroxymethyltransferase pseudogene SHMT-ps1 is unique to the order Primates.

BACKGROUND: The serine hydroxymethyltransferase processed pseudogene SHMT-ps1 has been suggested to be unique to the order Primates because of the failure to amplify this sequence by PCR from genomic DNAs of any non-primate mammal species. Here, 'molecular beacon' probes specific to SHMT-ps1 were used in an attempt to verify this suggestion. RESULTS: In a search for SHMT-ps1-specific sequences using molecular beacons across a range of mammalian species, SHMT-ps1 was only found in primates. The molecular beacon assays also showed that SHMT-ps1 is present in both Old World and New World species but not among prosimians. CONCLUSIONS: These results suggest that SHMT-ps1 originated close to the origin of the Anthropoidea, some 40 to 50 million years ago.

Animals↗
PubMed2003

Protein prenyltransferases: anchor size, pseudogenes and parasites.

Lipid modification of eukaryotic proteins by protein prenyltransferases is required for critical signaling pathways, cell cycle progression, cytoskeleton remodeling, induction of apoptosis and vesicular trafficking. This review analyzes the influence of distinct states of sequential posttranslational processing that can be obtained after single or double prenylation, reversible palmitoylation, proteolytic cleavage of the C-terminus and possible reversible carboxymethylation. This series of modifications, as well as the exact length of the prenyl anchor, are determinants in protein-membrane and specific protein-protein interactions of protein prenyltransferase substrates. Furthermore, the occurrence and distribution of pseudogenes of protein prenyltransferase subunits are discussed. Besides being developed as anti-cancer agents, prenyltransferase inhibitors are effective against an increasing number of parasitic diseases. Extensive screens for protein prenyltransferases in genomic data of fungal and protozoan pathogens unveil a series of new pharmacologic targets for prenyltransferase inhibition, including the parasites Brugia malayi, Onchocerca volvulus, Aspergillus nidulans, Pneumocystis carinii, Entamoeba histolytica, Strongyloides stercoralis, Trichinella spiralis and Cryptosporidium parvum.

Animals↗
PubMed2005

Fixation of the human-specific CMP-N-acetylneuraminic acid hydroxylase pseudogene and implications of haplotype diversity for human evolution.

The human CMP-N-acetylneuraminic acid hydroxylase gene (CMAH) suffered deletion of an exon that encodes an active center for the enzyme approximately 3.2 million years ago (MYA). We analyzed a 7.3-kb intronic region of 132 CMAH genes to explore the fixation process of this pseudogene and the demographic implication of its haplotype diversity. Fifty-six variable sites were sorted into 18 different haplotypes with significant linkage disequilibrium. Despite the rather low nucleotide diversity, the most recent common ancestor at CMAH dates to 2.9 MYA. This deep genealogy follows shortly after the original exon deletion, indicating that the deletion has fixed in the population, although whether this fixation was facilitated by natural selection remains to be resolved. Remarkable features are exceptionally long persistence of two lineages and the confinement of one lineage in Africa, implying that some African local populations were in relative isolation while others were directly involved in multiple African exoduses of the genus Homo. Importantly, haplotypes found in Eurasia suggest interbreeding between then-contemporaneous human species. Although population structure within Africa complicates the interpretation of phylogeographic information of haplotypes, the data support a single origin of modern humans, but not with complete replacement of archaic inhabitants by modern humans.

Animals↗
PubMed2002

Presence of the RHD pseudogene and the hybrid RHD-CE-D(s) gene in Brazilians with the D-negative phenotype.

The molecular basis for RHD pseudogene or RHD Psi is a 37-bp insertion in exon 4 of RHD. This insertion, found in two-thirds of D-negative Africans, appears to introduce a stop codon at position 210. The hybrid RHD-CE-Ds, where the 3' end of exon 3 and exons 4 to 8 are derived from RHCE, is associated with the VS+V- phenotype, and leads to a D-negative phenotype in people of African origin. We determined whether Brazilian blood donors of heterogeneous ethnic origin had RHD Psi and RHD-CE-Ds. DNA from 206 blood donors were tested for RHD Psi by a multiplex PCR that detects RHD, RHD Psi and the C and c alleles of RHCE. The RHD genotype was determined by comparison of size of amplified products associated with the RHD gene in both intron 4 and exon 10/3'-UTR. VS was determined by amplification of exon 5 of RHCE, and sequencing of PCR products was used to analyze C733G (Leu245Val). Twenty-two (11%) of the 206 D-negative Brazilians studied had the RHD Psi, 5 (2%) had the RHD-CE-Ds hybrid gene associated with the VS+V- phenotype, and 179 (87%) entirely lacked RHD. As expected, RHD was deleted in all the 50 individuals of Caucasian descent. Among the 156 individuals of African descent, 22 (14%) had inactive RHD and 3% had the RHD-CE-Ds hybrid gene. These data confirm that the inclusion of two different multiplex PCR for RHD is essential to test the D-negative Brazilian population in order to avoid false-positive typing of polytransfused patients and fetuses.

Black People↗
PubMed2000

A tRNA pseudogene in the archaeon Methanococcus jannaschii.

While searching the first completely sequenced genome of the archaeon Methanococcus jannaschii for a small RNA gene, we discovered a 5' truncated gene of a transfer RNA (tRNA(Ser-UCR)) at position 334,431-334,486; including the CCA-end that exactly matched the 3' terminal domain of the annotated M. jannaschii tRNA(Ser-UCR) gene located at position 303,992-304,081. This truncated tRNA gene covering 56 nucleotides (about 2/3) of the genuine tRNA represents, to the best of our knowledge, the first described tRNA pseudogene in the archaeal domain.

Base Sequence↗
PubMed2001

Genomic organization of the murine G protein beta subunit genes and related processed pseudogenes.

The functional significance of heterotrimeric guanine nucleotide binding protein (G protein) for the many physiological processes including the molecular mechanisms of drug addiction have been described. In investigating the changes of mRNA expression after acute psychostimulant administration, we previously identified a cDNA encoding a G protein beta1 subunit (Gbeta1) that was increased up to four-fold in certain brain regions after administration of psychostimulants. The mouse Gbeta1 gene (the mouse genetic symbol, GNB1) was mapped to chromosome 4, but little was known of its genetic features. To characterize the GNB1 gene further, we have cloned and analyzed the genomic structures of the mouse GNBI gene and its homologous sequences. The GNBI gene spans at least 50 kb, and consists of 12 exons and 11 introns. The exon/intron boundaries were determined and found to follow the GT/AG rule. Exons 3-11 encode the Gbeta1 protein, and the exon 2 is an alternative, resulting in putative two splicing variants. Although intron 11 is additional for GNBI compared with GNB2 and GNB3, the intron positions within the protein coding region of GNB1, GNB2 and GNB3 are identical, suggesting that GNB1 should have diverged from the ancestral gene family earlier than the genes for GNB2 and GNB3. We also found the 5'-truncated processed pseudogenes with 71-89% similarities to GNBI mRNA sequence, suggesting that the truncated cDNA copies, which have been reverse-transcribed from a processed mRNA for GNB1, might have been integrated into several new locations in the mouse genome.

Animals↗
PubMed1995

Cloning and chromosomal localization of a pseudogene corresponding to a mRNA for a soluble IL-6 receptor.

A polymerase chain reaction assay (Lust J.A. et al. (1992). Cytokine 4:96-100) was used to detect a mRNA coding for a soluble IL-6 receptor in human hepatoma cells. In addition to the expected amplification product, we found a sequence (SR4) which could be aligned to it with 78% identity. After cloning and sequencing a genomic 2.5-2.7 kB EcoRI fragment containing SR4, this sequence turned out to be part of a pseudogene corresponding to the transmembrane domain deleted soluble IL-6 receptor. Screening of a panel of interspecies hybrids revealed that it maps to chromosome 9.

Antigens, CD↗
PubMed2003

Analysis of the TCR beta variable gene repertoire in chimpanzees: identification of functional homologs to human pseudogenes.

Chimpanzees are used for a variety of disease models such as hepatitis C virus (HCV) infection, where Ag-specific T cells are thought to be critical for resolution of infection. The variable segments of the TCR alphabeta genes are polymorphic and contain putative binding sites for MHC class I and II molecules. In this study, we performed a comprehensive analysis of genes that comprise the TCR beta variable gene (TCRBV) repertoire of the common chimpanzee Pan troglodytes. We identified 42 P. troglodytes TCRBV sequences representative of 25 known human TCRBV families. BV5, BV6, and BV7 are multigene TCRBV families in humans and homologs of most family members were found in the chimpanzee TCRBV repertoire. Some of the chimpanzee TCRBV sequences were identical with their human counterparts at the amino acid level. Notably four successfully rearranged TCRBV sequences in the chimpanzees corresponded to human pseudogenes. One of these TCR sequences was used by a cell line directed against a viral CTL epitope in an HCV-infected animal indicating the functionality of this V region in the context of immune defense against pathogens. These data indicate that some TCRBV genes maintained in the chimpanzee have been lost in humans within a brief evolutionary time frame despite remarkable conservation of the chimpanzee and human TCRBV repertoires. Our results predict that the diversity of TCR clonotypes responding to pathogens like HCV will be very similar in both species and will facilitate a molecular dissection of the immune response in chimpanzee models of human diseases.

Amino Acid Sequence↗
PubMed2004

Genetic makeup of the DR region in rhesus macaques: gene content, transcripts, and pseudogenes.

In the human population, five major HLA-DRB haplotypes have been identified, whereas the situation in rhesus macaques (Macaca mulatta) is radically different. At least 30 Mamu-DRB region configurations, displaying polymorphism with regard to number and combination of DRB loci present per haplotype, have been characterized. Until now, Mamu-DRB region genes have been studied mainly by genomic sequencing of polymorphic exon 2 segments. However, relatively little is known about the expression status of these genes. To understand which exon 2 segments may represent functional genes, full-length cDNA analyses of -DRA and -DRB were initiated. In the course of the study, 11 cDRA alleles were identified, representing four distinct gene products. Amino acid replacements are confined to the leader peptide and cytoplasmatic tail, whereas residues of the alpha1 domain involved in peptide binding, are conserved between humans, chimpanzees, and rhesus macaques. Furthermore, from the 11 Mamu-DRB region configurations present in this panel, 28 cDRB alleles were isolated, constituting 12 distinct cDRA/cDRB configurations. Evidence is presented that a single configuration expresses maximally up to three -DRB genes. For some exon 2 DRB sequences, the corresponding transcripts could not be detected, rendering such alleles as probable pseudogenes. The full-length cDRA and cDRB sequences are necessary to construct Mhc class II tetramers, as well as transfectant cell lines. As the rhesus macaque is an important animal model in AIDS vaccine studies, the information provided in this communication is essential to define restriction elements and to monitor immune responses in SIV/simian human immunodeficiency virus-infected rhesus macaques.

Alleles↗
PubMed2000

The presence of an RHD pseudogene containing a 37 base pair duplication and a nonsense mutation in africans with the Rh D-negative blood group phenotype.

Antigens of the Rh blood group system are encoded by 2 homologous genes, RHD and RHCE, that produce 2 red cell membrane proteins. The D-negative phenotype is considered to result, almost invariably, from homozygosity for a complete deletion of RHD. The basis of all PCR tests for predicting fetal D phenotype from DNA obtained from amniocytes or maternal plasma is detection of the presence of RHD. These tests are used in order to ascertain the risk of hemolytic disease of the newborn. We have identified an RHD pseudogene (RHD psi) in Rh D-negative Africans. RHDpsi contains a 37 base pair (bp) insert in exon 4, which may introduce a stop codon at position 210. The insert is a sequence duplication across the boundary of intron 3 and exon 4. RHDpsi contains another stop codon in exon 6. The frequency of RHDpsi in black South Africans is approximately 0.0714. Of 82 D-negative black Africans, 66% had RHDpsi, 15% had the RHD-CE-D hybrid gene associated with the VS+ V- phenotype, and only 18% completely lacked RHD. RHDpsi is present in about 24% of D-negative African Americans and 17% of D-negative South Africans of mixed race. No RHD transcript could be detected in D-negative individuals with RHDpsi, probably as a result of nonsense-mediated mRNA decay. Existing PCR-based methods for predicting D phenotype from DNA are not suitable for testing Africans or any population containing a substantial proportion of people with African ethnicity. Consequently, we have developed a new test that detects the 37 bp insert in exon 4 of RHDpsi. (Blood. 2000; 95:12-18)

Amino Acid Sequence↗
PubMed2002

[Distribution of poly(ADP-ribose) polymerase pseudogene polymorphism and association with susceptibility to lung cancer in Chinese people].

OBJECTIVE: To study the distribution of poly(ADP-ribose) polymerase(PARP) pseudogene polymorphism and the association with susceptibility to lung cancer in Chinese people. METHODS: The subjects of this study included 63 patients with lung cancer and 82 healthy controls matched in gender and age. Genome DNA was extracted from white blood cells. Products from PCR with a pair of specific primer were electrophoresized in agarose including EB. Under ultraviolet, observation and imaging were performed. RESULTS: There was no significant difference in genotype between the cases and controls. The frequencies of B allele in cases and controls were 0.095 and 0.116 respectively. Whether there was B allele or not, smoking was a risk factor of lung cancer (P<0.05). As the genotype was AA and AB or BB, smoking OR was 2.28 and 4.83 respectively. Among non-smokers, the risk at lung cancer did not increase in AB or BB genotypes(P=0.202). CONCLUSION: Frequency of B allele is relatively lower in Chinese people than in other races. In smokers, B allele may be a susceptible marker of lung cancer, and there is synergistic function between B allele and smoking.

Adult↗
PubMed1992

Isolation of a new human pseudogene for proliferating cell nuclear antigen.

A new gene, which cross-hybridized with a rat PCNA cDNA probe, has been isolated from a human genomic cosmid library. A comparison of the gene with the human PCNA cDNA revealed 71% homology for the nucleotide sequences. This gene completely lacks introns and has traces of a polyA tail which the messenger RNA of the active gene retains. These facts indicate that this gene was generated by the reverse-transcription of a processed RNA for PCNA and exists as a PCNA pseudogene in the human genome.

Animals↗
PubMed2002

[Cloning and identification of a mouse zinc finger protein gene ZF-12-related pseudogene].

The mouse zinc finger protein ZF-12 gene is homologous to human gene and encodes a protein of 368 amino acids, which contains four tandem C2H2-type zinc finger motifs in the N-terminal and one SCAN domain in the C-terminal. Some recent studies suggest that ZNF191 might be a hepatocarcinogenesis-associated gene. We screened a mouse lambda genomic library with a human ZNF191 cDNA probe and isolated a ZF-12-like gene, named ZF12p (GenBank AY040222). This intronless gene closely resembles ZF-12 but displays several mutations, suggesting that ZF12p represents a ZF-12-related pseudogene. RT-PCR analysis on total RNA from mouse tissue and bioinformatis analysis on promoter region of ZF12p gene, suggest the transcripts of ZF12p may be not synthesized. BLAST on the data of the human genome in the GenBank with ZNF191 cDNA and Southern blotting show there is no any psedogene related to ZNF191 gene in the human genome. The high similarity of ZF12p to ZF-12 might be of considerable importance for mutation and evolution analysis of ZF-12.

Amino Acid Sequence↗
PubMed1992

Chromosomal assignment of two human B-raf(Rmil) proto-oncogene loci: B-raf-1 encoding the p94Braf/Rmil and B-raf-2, a processed pseudogene.

The B-raf gene is the human homolog of the avian c-Rmil proto-oncogene encoding a 94-kDa serine/threonine kinase detected in avian cells. We have previously shown that this protein contains amino-terminal sequences not found in other proteins of the mil/raf gene family. These sequences are encoded by three exons in the avian genome. We report that these three exons are conserved in the human B-raf gene and that they encode an amino acid sequence similar to that of the avian c-Rmil gene, indicating that in both avian and mammalian species the product of the B-raf/c-Rmil gene is a 94-kDa protein. We also identified two human B-raf loci: B-raf-1, located on chromosome 7q34, which encodes the functional B-raf/Rmil gene product, and B-raf-2, an inactive processed pseudogene located on chromosome Xq13.

Amino Acid Sequence↗
PubMed2005

Stress-induced Rim2/Hipa pseudogene of rice exhibits alternative tailing and splicing during transcription.

The rice Rim2/Hipa is a unique stress-induced transposon superfamily recently identified in Oryza genomes. In the present study, we conducted genome-wide screening of full-length Rim2 cDNA from the pathogen-induced cDNA libraries and mining of cDNA databases. Four indica and two japonica types of transcripts were identified, which were transcribed from the same Rim2 pseudogene Rim2-42 that contains premature stop codons in the TNP2-TPase coding region. These data demonstrated that the processing of the Rim2 transcripts exhibited variations within and between the two subspecies. These transcripts were found to be produced by alternative transcription (tailing) or splicing from Rim2-42 under stress conditions. An additional Rim2-like transcript (Rim2-XET), a chimera of Rim2 and XET genes, were also found to be derived from read-through. These results show that the Rim2 transposon probably loses its transposition capacity during evolution, and that Rim2-42 inserts downstream of the stress-inducible XET promoter, resulting in Rim2 transcript accumulation upon pathogen attack.

Base Sequence↗
PubMed1990

The mammalian genome contains a high proportion of processed pseudogenes corresponding to ribosomal protein L19.

The mammalian genome contains multiple copies of ribosomal protein (rp) L19-related sequences. Screening of mouse and rat genomic libraries with cloned rpL19 cDNA yielded seventeen independent lambda Charon 4A recombinant phages containing twelve and five genes for mouse and rat rpL19, respectively. Structural analysis indicated that all of these rpL19 genes contain the entire coding sequence (approx. 700 bp) but lack introns. The nucleotide sequence of a mouse gene (rpL19-17), exhibiting the highest homology with the mouse rpL19 cDNA, revealed genetic lesions which would preclude the translation of an intact protein, from a putative transcript. Based on these features we propose that these clones represent processed genes of which most, if not all, are pseudogenes.

Animals↗