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Death receptor 3 (DR3) gene duplication in a chromosome region 1p36.3: gene duplication is more prevalent in rheumatoid arthritis

Genes & Immunity volume 5, pages 439–443 (2004)Cite this article

Abstract

The death receptor 3 (DR3) gene is a member of the apoptosis-inducing Fas gene family. In the current study, fluorescence in situ hybridization (FISH) and Fiber-FISH revealed the existence of a second DR3 gene ∼200 kb upstream of the original DR3 gene. The existence of the duplicated DR3 gene was confirmed by sequencing the corresponding human artificial chromosome clones as well as with quantitative PCR that measured the ratio of the DR3 gene mutation (Rm), intrinsic to rheumatoid arthritis (RA) patients, by simultaneous amplification of the normal and mutated DR3 sequences. The DR3 gene duplication measured by FISH was found to be more frequent in patients with RA as compared to healthy individuals. We therefore surmise that the human DR3 gene can be duplicated and that this gene duplication is more prevalent in patients with RA.

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Acknowledgements

We thank Professor J Inazawa and Dr F Saito-Ohara at the Tokyo medical and dental University for their technical advise on FISH and Fiber-FISH, and Drs Y Konishi, H Kawasaki, Y Miura, K Komai and K Murayama at Kobe University for useful advice. We also thank Dr M Lamphier for critical reading of the manuscript. This study is expected to be a doctoral thesis of KO. This investigation was supported in part by a Grand-in-Aid for Scientific Research of the Ministry of Education, Culture, Sports, Science and Technology of Japan, Nos. 14657117 to KO and 13204059 to SS. This research was also supported by a grant for 21st Century COE Program, ‘Center of Excellence for Signal Transduction disease: Diabetes Mellitus as Model’ from the Ministry of Education, Culture, Sports, Science and Technology of Japan to SS.

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Authors and Affiliations

  1. Department of Rheumatology, Kobe University FHS School of Medicine, Kobe, Japan

    K Osawa, N Takami, A Hashiramoto & S Shiozawa

  2. Division of Bioregulation, Kobe University Graduate School of Medicine, Kobe, Japan

    K Osawa, N Takami, A Hashiramoto & S Shiozawa

  3. Department of Rheumatology, Konan Kakogawa Hospital, Kakogawa, Japan

    K Shiozawa

  4. Rheumatic Diseases Division, Kobe University Hospital, Kobe, Japan

    A Hashiramoto & S Shiozawa

  5. Investigator of the Center of Excellence (COE), Japan

    S Shiozawa

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  1. K Osawa
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  2. N Takami
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  3. K Shiozawa
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  4. A Hashiramoto
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Correspondence to S Shiozawa.

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Osawa, K., Takami, N., Shiozawa, K. et al. Death receptor 3 (DR3) gene duplication in a chromosome region 1p36.3: gene duplication is more prevalent in rheumatoid arthritis. Genes Immun 5, 439–443 (2004). https://doi.org/10.1038/sj.gene.6364097

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