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Immunogenetics

, Volume 63, Issue 8, pp 467–474 | Cite as

Exact break point of a 50 kb deletion 8 kb centromeric of the HLA-A locus with HLA-A*24:02: the same deletion observed in other A*24 alleles and A*23:01 allele

  • Shigeki Mitsunaga
  • Yuko Okudaira
  • Nanae Kunii
  • Tailin Cui
  • Kazuyoshi Hosomichi
  • Akira Oka
  • Yasuo Suzuki
  • Yasuhiko Homma
  • Shinji Sato
  • Ituro Inoue
  • Hidetoshi InokoEmail author
Original Paper
  • 137 Downloads

Abstract

In a structural aberration analysis of patients with arthritis mutilans, a 50 kb deletion near the HLA-A locus with HLA-A*24:02 allele was detected. It was previously reported that HLA-A*24:02 haplotype harbored a large-scale deletion telomeric of the HLA-A gene in healthy individuals. In order to confirm that the deletion are the same in patients with arthritis mutilans and in healthy individuals, and to identify the break point of this deletion, the boundary sequences across the deletion in A*24:02 was amplified by polymerase chain reaction (PCR) as a 3.7 kb genomic fragment and subjected to nucleotide sequence determination. A comparison of these genomic sequences with those of the non-A*24:02 haplotype revealed that the deleted genomic region spanning 50 kb was flanked by 3.7 kb repetitive element-rich segments homologous to each other on both sides in non-A*24. The nucleotide sequences of the PCR products were identical in patients with arthritis mutilans and in healthy individuals, revealing that the deletion linked to A*24:02 is irrelevant to the onset of arthritis mutilans. The deletion was detected in all other A*24 alleles so far examined but not in other HLA-A alleles, except A*23:01. This finding, along with the phylogenic tree of HLA-A alleles and the presence of the 3.7 kb highly homologous segments at the boundary of the deleted genomic region in A*03 and A*32, may suggest that this HLA-A*24:02-linked deletion was generated by homologous recombination within two 3.7 kb homologous segments situated 50 kb apart in the ancestral A*24 haplotype after divergence from the A*03 and A*32 haplotypes.

Keywords

HLA-A*24 Deletion Arthritis mutilans Evolution 

Notes

Acknowledgments

We would like to thank the DNA donors and supporting medical staff for making this study possible. We thank Ms. Hisako Kawata from the Education and Research Support Center, Tokai University School of Medicine for the technical assistance. We also thank Dr. Koich Kashiwase for providing A*23:01 samples. This work was supported, in part, by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Health, Labour, and Welfare.

Conflicts of interest

None

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Shigeki Mitsunaga
    • 1
  • Yuko Okudaira
    • 1
  • Nanae Kunii
    • 1
  • Tailin Cui
    • 1
  • Kazuyoshi Hosomichi
    • 1
  • Akira Oka
    • 1
  • Yasuo Suzuki
    • 2
  • Yasuhiko Homma
    • 3
  • Shinji Sato
    • 2
  • Ituro Inoue
    • 1
  • Hidetoshi Inoko
    • 1
    Email author
  1. 1.Department of Molecular Life Sciences, Division of Basic Medical Science and Molecular MedicineTokai University School of MedicineKanagawaJapan
  2. 2.Department of Internal MedicineTokai University School of MedicineKanagawaJapan
  3. 3.Department of Clinical Health ScienceTokai University School of MedicineKanagawaJapan

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