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

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Abstract

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-β 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.

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Authors and Affiliations

  1. Department of Molecular Life Science, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan

    Yasunari Matsuzaka, Koichi Okamoto, Tomotaka Mabuchi, Akira Oka, Gen Tamiya, Jerzy K. Kulski & Hidetoshi Inoko

  2. Department of Dermatology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan

    Tomotaka Mabuchi, Mariko Iizuka & Akira Ozawa

  3. Fuji-Gotemba Research Laboratories, Chugai Pharmaceuticals. Co. Ltd., 1-135, Komakado, Gotemba, Shizuoka, Japan

    Koichi Okamoto

  4. Centre for Bioinformatics and Biological Computing, School of Information Technology, Division of Arts, Murdoch University, Murdoch, 6150, Western Australia

    Jerzy K. Kulski

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  1. Yasunari Matsuzaka
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  2. Koichi Okamoto
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  3. Tomotaka Mabuchi
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  4. Mariko Iizuka
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  5. Akira Ozawa
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  6. Akira Oka
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  7. Gen Tamiya
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  8. Jerzy K. Kulski
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  9. Hidetoshi Inoko
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Corresponding author

Correspondence to Hidetoshi Inoko.

Additional information

GenBank accession number for human TXNRD3NT1 cDNA is AB113648.

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Matsuzaka, Y., Okamoto, K., Mabuchi, T. et al. Identification and characterization of novel variants of the thioredoxin reductase 3 new transcript 1 TXNRD3NT1. Mamm Genome 16, 41–49 (2005). https://doi.org/10.1007/s00335-004-2416-y

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  • DOI: https://doi.org/10.1007/s00335-004-2416-y

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