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PubMed1990

Isolation and characterization of the human hepatic lipase gene.

Overlapping bacterial phage and cosmid genomic clones were isolated spanning an area of approximately 60 kilobases that contains the human hepatic lipase (HL) gene. It is composed of 9 exons spanning approximately 35 kilobases of DNA. The entire coding regions, the 5'-flanking sequences, and the exon-intron junctions were sequenced. The intron positions correspond to those of human lipoprotein lipase and canine pancreatic lipase, supporting the concept that these genes constitute a dispersed gene family of lipases and have evolved by duplication of a common ancestral gene. A region of the HL gene, which displays a significant homology with various other lipolytic enzymes and contains the putative catalytic site serine residue of HL, was encoded by exon 4. A major transcription start site of the human HL gene was located by primer extension analysis, 43 nucleotides upstream of the translation initiation codon. Two possible promoter elements were located 25 and 63 nucleotides upstream of the transcription initiation site: a "TATA" box-like sequence, TAATA, and a sequence found in the promoter region of many liver-specific genes, AGGTTAATTATTAAT. In addition, sequences homologous to glucocorticoid and cAMP-responsive elements were identified in the 5'-nontranscribed region.

Amino Acid Sequence↗
PubMed1991

Organization of the mouse acid beta-galactosidase gene.

Overlapping murine genomic DNA fragments containing the entire cDNA sequence were isolated from a cosmid library prepared from the DBA/2J strain of mice. The gene is more than 80-kb long, consisting of 16 exons. All of the exon-intron boundaries have been defined. The organization of the gene is highly conserved between the murine and human genes at least for the several exons and introns for which information for the human gene is available [Morreau et al., J. Biol. Chem. 264:20655, 1989]. Primer extension and RNase protection experiments indicated the presence of three potential transcription initiation sites, which are preceded by GC-rich SP1 binding sites but without typical TATA or CAT boxes, as is often the case for genes coding for housekeeping proteins. Compared to the cDNA sequence from C57BL/6J mouse, there were five nucleotide polymorphisms in the protein-coding region, two of which resulted in altered amino acids.

Animals↗
PubMed2006

The human ortholog of the rodent testis-specific ABC transporter Abca17 is a ubiquitously expressed pseudogene (ABCA17P) and shares a common 5' end with ABCA3.

BACKGROUND: During the past years, we and others discovered a series of human ATP-binding cassette (ABC) transporters, now referred to as ABC A-subfamily transporters. Recently, a novel testis-specific ABC A transporter, Abca17, has been cloned in rodent. In this study, we report the identification and characterization of the human ortholog of rodent Abca17. RESULTS: The novel human ABC A-transporter gene on chromosome 16p13.3 is ubiquitously expressed with highest expression in glandular tissues and the heart. The new ABC transporter gene exhibits striking nucleotide sequence homology with the recently cloned mouse (58%) and rat Abca17 (51%), respectively, and is located in the syntenic region of mouse Abca17 indicating that it represents the human ortholog of rodent Abca17. However, unlike in the mouse, the full-length ABCA17 transcript (4.3 kb) contains numerous mutations that preclude its translation into a bona fide ABC transporter protein strongly suggesting that the human ABCA17 gene is a transcribed pseudogene (ABCA17P). We identified numerous alternative ABCA17P splice variants which are transcribed from two distinct transcription initiation sites. Genomic analysis revealed that ABCA17P borders on another ABC A-subfamily transporter - the lung surfactant deficiency gene ABCA3. Surprisingly, we found that both genes overlap at their first exons and are transcribed from opposite strands. This genomic colocalization and the observation that the ABCA17P and ABCA3 genes share significant homologies in several exons (up to 98%) suggest that both genes have evolved by gene duplication. CONCLUSION: Our results demonstrate that ABCA17P and ABCA3 form a complex of overlapping genes in the human genome from which both non-coding and protein-coding ABC A-transporter RNAs are expressed. The fact that both genes overlap at their 5' ends suggests interdependencies in their regulation and may have important implications for the functional analysis of the disease gene ABCA3. Moreover, this is the first demonstration of the expression of a pseudogene and its parent gene from a common overlapping DNA region in the human genome.

ATP-Binding Cassette Transporters↗
PubMed2004

Detecting overlapping coding sequences with pairwise alignments.

MOTIVATION: Overlapping gene coding sequences (CDSs) are particularly common in viruses but also occur in more complex genomes. Detecting such genes with conventional gene-finding algorithms can be difficult for several reasons. If an overlapping CDS is on the same read-strand as a known CDS, then there may not be a distinct promoter or mRNA. Furthermore, the constraints imposed by double-coding can result in atypical codon biases. However, these same constraints lead to particular mutation patterns that may be detectable in sequence alignments. RESULTS: In this paper, we investigate several statistics for detecting double-coding sequences with pairwise alignments--including a new maximum-likelihood method. We also develop a model for double-coding sequence evolution. Using simulated sequences generated with the model, we characterize the distribution of each statistic as a function of sequence composition, length, divergence time and double-coding frame. Using these results, we develop several algorithms for detecting overlapping CDSs. The algorithms were tested on known overlapping CDSs and other overlapping open reading frames (ORFs) in the hepatitis B virus (HBV), Escherichia coli and Salmonella typhimurium genomes. The algorithms should prove useful for detecting novel overlapping genes--especially short coding ORFs in viruses. AVAILABILITY: Programs may be obtained from the authors. SUPPLEMENTARY INFORMATION: http://biochem.otago.ac.nz/double.html.

Algorithms↗
PubMed2026

Comparative in silico analysis of Apis mellifera immune responses to Varroa destructor and Tropilaelaps mercedesae: Common and mite-specific molecular signatures.

Parasitic mites Varroa destructor and Tropilaelaps mercedesae represent major threats to global honey bee (Apis mellifera) health and productivity, yet comparative molecular insights into host responses remain limited. To address this, we systematically compiled published studies (2015-2025) reporting genes associated with honey bee interactions with V. destructor (11 studies, 87 genes), T. mercedesae (4 studies, 35 genes), and hygienic behavior (6 studies, 44 genes). Gene identifiers were harmonized to the Amel_HAv3.1 genome assembly, yielding three non-redundant sets: 64 Varroa-associated, 34 Tropilaelaps-associated, and 44 hygienic behavior-associated genes. Venn analysis identified 10 overlapping genes (including A0A088A8D5, A0A088ADL8, ABAE_APIME, Def1, Def2, Gapdh, HYTA_APIME, Imd, LOC726783, and Vg), suggesting conserved defense mechanisms, while 41 and 24 genes were uniquely associated with Varroa and Tropilaelaps, respectively. Enrichment analyses revealed Varroa-responsive genes were enriched in immune processes, chitin catabolism, and signaling pathways (Toll/Imd, MAPK, Wnt). Tropilaelaps-associated genes were enriched for antibacterial defense and stress response, with Toll/Imd signaling as the sole significantly enriched pathway. Overlapping genes reinforced core innate immunity activation. Protein-protein interaction network centrality analysis identified key hub genes: Def1, HYTA_APIME, ABAE_APIME, PPO, Imd, PGRP-LC, Vg for Varroa; and ACPH1_APIME, MRJP1, Vg, LOC726783 for Tropilaelaps. Results demonstrate that, despite differences in mite biology, honey bees show a conserved immune response against both parasites, centered on antibacterial defense, humoral immunity, and activation of the Toll/Imd pathway. Although limited by the in-silico nature and research asymmetries reflecting Tropilaelaps' emergence, this curated resource establishes a comprehensive framework for elucidating shared and distinct molecular defense mechanisms. Ultimately, this approach prioritizes diagnostic markers and candidate genes for functional validation and breeding strategies to enhance colony resilience against mite‑driven disease globally.

Animals↗
PubMed2024

Biomarkers related to m6A and succinic acid metabolism in papillary thyroid carcinoma.

BACKGROUND: Studies have shown that m6A modification is related to the occurrence and development of papillary thyroid carcinoma (PTC). The disorder of succinic acid metabolism is associated with the occurrence and development of various tumors. However, there are few studies based on m6A and succinate metabolism-related genes (SMRGs) in PTC. METHODS: The TCGA-Thyroid carcinoma (THCA), GSE33630, 1159 SMRGs, and 23 m6A regulatory factors were collected from the online databases. Subsequently, the differentially expressed genes (DEGs) were selected between PTC (Tumor) and Normal samples. The overlapping genes among the DEGs, m6A, and SMRGs were applied to screen the biomarkers. Using the 3 machine-learning algorithms, the biomarkers were determined based on the overlapping genes. Next, the biomarkers were evaluated by the ROC curve and expression analysis in TCGA-THCA and GSE33630. Then, the overall survival (OS) differences were compared between the high-and low-expression biomarkers. Finally, immune infiltration analysis, molecular regulatory network, and drug prediction were performed based on the biomarkers. RESULTS: In TCGA-THCA, there were 2800 DEGs between and Normal samples, and then 7 overlapping genes were obtained. Importantly, ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ were determined as biomarkers with excellent diagnostic efficiency (AUC > 0.7). In PTC samples, ADK and TNFRSF10B were high-expressed while CYP7B1, FGFR2, and CPQ were low-expressed. Especially, the high-expression groups of ADK had a better prognosis, while the high-expression groups of CYP7B1, FGFR2, and CPQ had a worse prognosis. Afterward, immune infiltration analysis found that 16 immune cells had infiltration differences between the Tumor and Normal samples. Finally, transcription factor SP1 could regulate CYP7B1 and TNFRSF10B. Moreover, Navitoclax was a potential drug for PTC patients. CONCLUSION: Overall, we described 5 biomarkers associated with adverse prognosis of PTC, including ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ. All these biomarkers were involved in succinate metabolism and m6A modification of RNA. This set of biomarkers should be explored further for their diagnostic value in PTC. Investigations into the mechanistic role of alteration of succinate metabolism and m6A modification of RNA pathways in the pathophysiology of PTC are warranted.

Humans↗
PubMed1980

Polyoma virus DNA: complete nucleotide sequence of the gene which codes for polyoma virus capsid protein VP1 and overlaps the VP2/VP3 genes.

The nucleotide sequence of part of the late region of the polyoma virus genome was determined. It contains coding information for the major capsid protein VP1 and the C-terminal region of the minor proteins VP2 and VP3. In the sequence with the same polarity as late mRNA's, all coding frames are blocked by termination codons in a region around 48 units on the physical map. This is the region where the N-terminus of VP1 and the C-termini of VP2 and VP3 have been located (T. Hunter and W. Gibson, J. Virol. 28:240-253, 1978; S. G. Siddell and A. E. Smith, J. Virol. 27:427-431, 1978; Smith et al., Cell 9:481-487, 1976). There are two long uninterrupted coding frames in the late region of polyoma virus DNA. One lies at the 5' end of the sequence and contains potential coding sequences for VP2 and VP3. The other contains 383 consecutive sense codons starting with the ATG at nucleotide position 1,218, extends from 47.5 to 25.8 units counterclockwise on the physical map, and is located where the VP1 gene has been mapped. The VP1 gene overlaps the genes for proteins VP2/VP3 by 32 nucleotides and uses a different coding frame. From the DNA sequence, the amino acid sequence of VP1 was predicted. The proposed VP1 sequence is in good agreement with other data, namely, with the partial N-terminal amino acid sequence and the total amino acid composition. The VP1 coding frame terminates with a TAA codon at 25.8 map units. This is followed by an AATAAA sequence, which may act as a processing signal for the viral late mRNA's. When both nucleotide and amino acid sequences are compared with their counterparts in the related simian virus 40, extensive homologies are found over the entire region of the two viral genomes. Maximum homology appears to occur in those regions which code for the C-termini of the VP1 proteins. The overlap region of VP1 with VP2/VP3 of polyoma virus is shorter by 90 nucleotides than is that of simian virus 40 and shows very limited homology with the simian virus 40 sequence. This leads to the suggestion that the overlap segments of both viruses have been freed from stringency imposed on drifting during evolution and that proteins VP2 and VP3 of polyoma virus may have been truncated by the appearance of a termination codon within the sequence.

Amino Acid Sequence↗
PubMed1987

Role of premature translational termination in the regulation of expression of the phi X174 lysis gene.

Expression of the phi X174 lysis (E) gene, a member of an overlapping gene pair, appears to depend on a frameshift-induced chain termination by ribosomes translating the upstream D gene. A -1 reading frameshift, possibly induced by misreading of an alanine codon as a doublet, causes ribosomes to terminate translation at two different sites, suggesting two modes of regulating expression of the E gene. One frameshift can cause translational termination at a stop codon(s) near the E gene ribosome binding site (RBS), resulting in reinitiation by ribosomes at the E gene RBS. Termination at a second site some 70 bases upstream from the E gene RBS, while too far away to allow ribosomal re-initiation at the E gene RBS, probably results in an unmasking of the message, allowing entry of a new ribosome at the E gene RBS.

Bacteriophage phi X 174↗
PubMed1994

Two divergent endo-beta-1,4-glucanase genes exhibit overlapping expression in ripening fruit and abscising flowers.

Two structurally divergent endo-beta-1,4-glucanase (EGase) cDNAs were cloned from tomato. Although both cDNAs (Cel1 and Cel2) encode potentially glycosylated, basic proteins of 51 to 53 kD and possess multiple amino acid domains conserved in both plant and microbial EGases, Cel1 and Cel2 exhibit only 50% amino acid identity at the overall sequence level. Amino acid sequence comparisons to other plant EGases indicate that tomato Cel1 is most similar to bean abscission zone EGase (68%), whereas Cel2 exhibits greatest sequence identity to avocado fruit EGase (57%). Sequence comparisons suggest the presence of at least two structurally divergent EGase families in plants. Unlike ripening avocado fruit and bean abscission zones in which a single EGase mRNA predominates, EGase expression in tomato reflects the overlapping accumulation of both Cel1 and Cel2 transcripts in ripening fruit and in plant organs undergoing cell separation. Cel1 mRNA contributes significantly to total EGase mRNA accumulation within plant organs undergoing cell separation (abscission zones and mature anthers), whereas Cel2 mRNA is most abundant in ripening fruit. The overlapping expression of divergent EGase genes within a single species may suggest that multiple activities are required for the cooperative disassembly of cell wall components during fruit ripening, floral abscission, and anther dehiscence.

Amino Acid Sequence↗
PubMed2005

C-Myc-independent restoration of multiple phenotypes by two C-Myc target genes with overlapping functions.

C-MYC, a transforming oncogene that is frequently overexpressed in many human cancers, regulates a variety of normal functions including cell cycle progression, apoptosis, and maintenance of cell size, morphology, and genomic integrity. Many target genes are modulated by c-Myc, and some can recapitulate a limited number of the above functions. Because most of these have been assessed in cells which also express endogenous c-Myc, however, it is not clear to what extent its proper regulation is also required. We show here that, in c-Myc nullizygous cells, two direct target genes, MT-MC1 and HMG-I, could each recapitulate multiple c-Myc phenotypes. Although these differ somewhat for the two genes, substantial overlap and cooperativity exist. The enforced expression of these two genes was also associated with the differential deregulation of some previously described c-Myc target genes, indicating the presence of a complex molecular circuitry. These observations argue that, despite the great diversity of gene regulation by c-Myc, many, although not all, of its functions can be phenocopied by a small subset of key downstream target genes. The approach described here should permit the identification of other target genes capable of further c-Myc-independent complementation.

Animals↗
PubMed1992

Organization and ordered expression of Caulobacter genes encoding flagellar basal body rod and ring proteins.

The biogenesis of the polar flagellum in Caulobacter crescentus is limited to a specific time in the cell cycle and to a specific site on the cell. The basal body is the first part of the flagellum to be assembled. In this report we identify a cluster of genes encoding basal body components and describe their transcriptional regulation. The genes in this cluster form an operon whose expression is controlled temporally. The first two genes encode homologs of FlgF and FlgG, which are the proximal and distal rod proteins, respectively. The sequences of the N and C termini of the Salmonella typhimurium flagellar axial proteins, rod, hook and HAP-1, known to be highly conserved, share a high degree of sequence identity with the FlgF and FlgG rod proteins of the distantly related, C. crescentus. Two additional genes in the flgF, flgG operon, flaD and flgH, both encode proteins with potentially cleavable signal sequences. The flgH gene, encoding the L-ring protein, is also transcribed from an internal promoter. Transcription from the flgF promoter initiates prior to initiation at the internal flgH promoter. The internal promoter and its activator site reside within the C-terminal coding sequence of the upstream flaD gene. This type of gene overlap is also observed in bacterial genes involved in cell division. Flagellum biogenesis, like cell division, is a morphogenic event that requires the orderly assembly of component proteins and the overlapping gene organization may affect this "ordering" of assembly. The promoters for the flgF operon and the flgH gene use sigma 54 to initiate transcription. The use of sigma 54 promoters, known to require cognate binding proteins, could allow the fine-tuning that provides the temporal ordering of flagellar gene transcription. In this context, we have found that the flgF operon and the distal flgI gene encoding the P-ring, share a sigma 54 activator sequence (class IIA) that differs from the flgH L-ring gene sigma 54 activator site (class IIB) and the hook cluster (class IIC) sigma 54 activator site. The sequential activation of these three subgroups of structural genes reflects the order of assembly of their gene products into the flagellum.

Amino Acid Sequence↗
PubMed1978

Nucleotide sequence of the J gene and surrounding untranslated regions of phage G4 DNA: comparison with phage phiX174.

A 290 nucleotide long region of the bacteriophage G4 genome including the end of the overlapping genes D and E, the entire gene J and the untranslated region between genes J and F has been sequenced and compared with the same region in bacteriophage phiX174. Deletions, insertions, duplications and single base changes in G4 relative to phiX174 have resulted in the following changes: the loss of the phiX174 overlapping gene Dtermination and gene J initiation codons, resulting in their separation by 32 untranslated nucleotides; the deletion of one third of the gene J coding region, so that the G4 protein is only 24 amino acids long compared with 37 amino acids in phiX174; and the establishment of a long untranslated region between G4 genes J and F, which despite many nucleotide changes retains the ability to form a stable hairpin loop in the same place and with the same geometry as in phiX174. The G4 overlapping gene E is longer than in phiX174 and extends beyond gene D. Sixteen nucleotides at the end of genes D and E in phiX174 are duplicated in G4 before gene J.

Base Sequence↗
PubMed1985

Characterisation of a Dictyostelium discoideum DNA fragment coding for a putative tRNAValGUU gene. Evidence for a single transcription unit consisting of two overlapping class III genes.

A genomic DNA fragment from Dictyostelium discoideum was characterized. This DNA, although 74% d(A + T)-rich, codes for a putative tRNAValGUU. The tRNAVal gene overlaps at its 5' half with another RNA polymerase III transcription unit. This RNA polymerase III transcription unit can be folded into a tRNA-like shape and is comprised of significant amounts of invariant and semi-invariant nucleotides present in all eukaryotic tRNAs. This unit contains the two promoter blocks defined for RNA polymerase III, which are homologous to recently defined promoter elements to the extent of 76-88% (A block) and 86-93% (B block) respectively [Sharp et al. (1981) Proc. Natl Acad. Sci. USA 78, 6657-6661]. Both of the overlapping class III genes are transcribed in germinal vesicle extracts prepared from Xenopus laevis oocytes as a single transcription unit, resulting in an unusually large product compared to primary transcripts of other tRNA genes. The unit is not transcribed in HeLa extracts but it competes very strongly for transcription factor(s) under the conditions of stable transcription complex formation. Although the whole unit is transcribed, it is believed that only one functional product is formed. Therefore we define the tRNA-like structure, coded for on this class III transcription unit, as a putative tRNA 'pseudogene' meaning that, although it is transcribed by RNA polymerase III, it is not likely to mature to a functional tRNA.

Base Sequence↗
PubMed2000

Multiple paths of sugar-sensing and a sugar/oxygen overlap for genes of sucrose and ethanol metabolism.

The two-fold purpose of this work is, first, to review current hypotheses for multiple paths of sugar-sensing in an oxygen-responsive context, and second, to present evidence for the extent of sugar/oxygen overlap regulating genes for sucrose and ethanol metabolism. Current data indicate that sugar signals in plants may be initiated by (a) hexokinases, (b) membrane sensors, (c) acetate and/or respiratory metabolites, and (d) other signals and/or crosstalk. Responses may also involve concurrent input along transduction paths by effectors such as energy charge, P status, and phytohormones. Prime candidates for initiation and/or integration of such signal integration include SNF1- and SCF-like, multi-enzyme complexes. In addition, different paths of sugar signal transduction may be linked to contrasting roles of responsive genes during feast, famine or pathogen attack. Oxygen can potentially alter sugar signals at several points, so its influence on feast and famine responses was initially tested with genes for sucrose metabolism in maize root tips. The Sus1 and Sh1 sucrose synthases in maize (typically up-regulated by carbohydrate abundance and deprivation, respectively) showed parallel responses to hypoxia (3% O2 [0.03l l-1 O2]) and anoxia (0% O2 [0l l-1 O2]) that were consistent with involvement of similar signals. In contrast, the differential sugar-responses of the lvr1 and lvr2 invertases were not evident under low oxygen, and both genes were rapidly repressed. A third response was evident in the marked, sugar-regulation of an oxygen-responsive Adh1 gene for alcohol dehydrogenase, which was sensitive to sugar availability from deficit to abundance, regardless of oxygen status (anaerobic to fully aerobic [40% O2 (0.04l l-1 O2)]. A clear interface is thus evident between sugar and oxygen signals, but this varies markedly with the genes involved and probable differences in respective transduction paths.

Carbohydrate Metabolism↗
PubMed2002

Reduced antigenicity of the hepatitis B virus HBsAg protein arising as a consequence of sequence changes in the overlapping polymerase gene that are selected by lamivudine therapy.

The prevalence of hepatitis B virus vaccine escape mutants has increased as a consequence of the introduction of global vaccination programs. Furthermore and as a consequence of the organization of the genome of hepatitis B virus (HBV) into overlapping reading frames, the selection of polymerase mutants during long-term lamivudine therapy can select viruses with changes in the overlapping S gene coding for the hepatitis B small antigen (HBsAg). We have investigated the role of lamivudine in selecting HBV mutants with antigenically altered HBsAg protein using pooled human vaccine sera in enzyme immunosorbent assays and radioimmunoassays. HBsAg proteins containing the vaccine escape mutations G145R and D144E/G145R demonstrated markedly reduced binding to anti-HBs antibody. HBsAg mutants including E164D, W196S, I195M, M198I, and E164D/I195M (corresponding to the polymerase protein changes of V519L, M550I, L526M/M550V V553I, and V519L/L526M/M550V) selected during lamivudine treatment also demonstrated reduced binding to anti-HBs antibody. These findings raise the possibility of lamivudine-resistant mutants arising that possess antigenically distinct HBsAg proteins.

DNA-Directed DNA Polymerase↗
PubMed2006

Detecting overlapping coding sequences in virus genomes.

BACKGROUND: Detecting new coding sequences (CDSs) in viral genomes can be difficult for several reasons. The typically compact genomes often contain a number of overlapping coding and non-coding functional elements, which can result in unusual patterns of codon usage; conservation between related sequences can be difficult to interpret--especially within overlapping genes; and viruses often employ non-canonical translational mechanisms--e.g. frameshifting, stop codon read-through, leaky-scanning and internal ribosome entry sites--which can conceal potentially coding open reading frames (ORFs). RESULTS: In a previous paper we introduced a new statistic--MLOGD (Maximum Likelihood Overlapping Gene Detector)--for detecting and analysing overlapping CDSs. Here we present (a) an improved MLOGD statistic, (b) a greatly extended suite of software using MLOGD, (c) a database of results for 640 virus sequence alignments, and (d) a web-interface to the software and database. Tests show that, from an alignment with just 20 mutations, MLOGD can discriminate non-overlapping CDSs from non-coding ORFs with a typical accuracy of up to 98%, and can detect CDSs overlapping known CDSs with a typical accuracy of 90%. In addition, the software produces a variety of statistics and graphics, useful for analysing an input multiple sequence alignment. CONCLUSION: MLOGD is an easy-to-use tool for virus genome annotation, detecting new CDSs--in particular overlapping or short CDSs--and for analysing overlapping CDSs following frameshift sites. The software, web-server, database and supplementary material are available at http://guinevere.otago.ac.nz/mlogd.html.

Algorithms↗
PubMed2005

Identification and characterization of novel variants of the thioredoxin reductase 3 new transcript 1 TXNRD3NT1.

We have identified and characterized a new gene sequence, TXNRD3NT1, whose transcripts, corresponding to the EST AA430236, were found by Affymetrix DNA chip analysis to be significantly down regulated in affected psoriatic tissue. The full-length cDNA of TXNRD3NT1 was isolated and characterized by combining 5'- and 3'-RACE (rapid amplication of cDNA ends) with screening a keratinocyte cDNA library, designing appropriate PCR primers, cloning amplified products, sequencing, and sequence analysis. Because part of this gene overlaps the previously described thioredoxin reductase 3 (TXNRD3) gene, we have named it TXNRD3NT1 (TXNRD3 new transcript 1). The full-length TXNRD3NT1 cDNA has 1133 nucleotides with a 251-bp 3-UTRand 2 poly(A)signal variants and 2 poly (A) sites. The TXNRD3NT1 cDNA ORF encodes for 133 amino acids, with the first four residues coding for a tubulin-beta mRNA autoregulation signal. Mapping the cDNA nucleotide sequence to the human genome sequence revealed that the TXNRD3NT1 gene has 4 exons located on Chromosome 3, at position 3q21. Exons 1 and 2 of the TXNRD3NT1 gene overlap with exons 15 and 16 of the thioredoxin reductase 2 gene which has different ORFs to that of TXNRD3NT1. The translation initiation codon ATG was found in exon 3 of the TXNRD3NT1 gene. RT-PCR showed that the full-length variant of the TXNRD3NT1 gene was expressed in only four issues (pancreas, esophagus, bone marrow, and keratinocytes) of the 30 different tissues tested. In most other tissues, an aberrant and truncated form of the transcript (i.e., missing exon 3 and part of exon 4) was detected. The result of a preliminary association study between psoriasis and single microsatellite marker of the TXNRD3NT1 gene suggests that it may not be a significant genetic determinant of psoriasis. However, we cannot exclude the possibility that other sequence variants may still exist within the TXNRD3NT1 gene. Sequence analysis of the TXNRD3NT1 gene from 8 psoriasis patients and 8 healthy controls revealed a number of synonymous SNPs that may be useful markers for future disease association studies.

Alternative Splicing↗