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Journal of Molecular Evolution

, Volume 48, Issue 3, pp 317–327 | Cite as

Genomic Organization Around the Centromeric End of the HLA Class I Region: Large-Scale Sequence Analysis

  • Masaaki  Yamazaki
  • Yoshio  Tateno
  • Hidetoshi  Inoko

Abstract.

We previously sequenced two regions around the centromeric end of HLA class I and the boundary between class I and class III. In this paper we analyze the two regions of about 385 kb and confirm, giving a new line of evidence, that the following two pairs of the genomic segments were duplicated in evolution: (i) a 43-kb genomic segment including the HLA-B gene showing the highest polymorphism among the classical HLA class I loci (class Ia) and a 40-kb segment including the HLA-C locus showing the lowest polymorphism and (ii) a 52-kb segment including the MIC (MHC class I chain related gene) B and a 35-kb segment including MICA. We also found that repetitive elements such as SINEs, LINEs, and LTRs occupy as much as 47% of nucleotides in this 385-kb region. This unusually high content of repetitive elements indicates that repeat-mediated rearrangements have frequently occurred in the evolutionary history of the HLA class Ia region. Analysis of LINE compositions within the two pairs of duplicated segments revealed that (i) LINEs in these regions had been dispersed prior to both the duplication of the HLA-B and -C loci and the duplication of the MICB and MICA loci, and (ii) the divergence of the HLA-B and -C loci occurred prior to the duplication of the MICA and MICB loci. To find novel genes responsible for HLA class I-associated or other diseases, we performed computer analysis applying GenScan and GRAIL to GenBank's dbEST. As a result, at least five as yet uncharacterized genes were newly mapped on the HLA class I centromeric region studied. These novel genes should be analyzed further to determine their relationships to diseases associated with this region.

Key words: HLA class I — Genome duplication — LINE — Gene hunting — Genome evolution 

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Copyright information

© Springer-Verlag New York Inc. 1999

Authors and Affiliations

  • Masaaki  Yamazaki
    • 1
  • Yoshio  Tateno
    • 3
  • Hidetoshi  Inoko
    • 2
  1. 1.BioScience Research Laboratory, Fujiya Co., Ltd., 228 Soya, Hadano, Kanagawa, 257-0031 JapanJP
  2. 2.Division of Molecular Life Sciences, Department of Genetic Information, School of Medicine, Tokai University, Boseidai, Isehara, Kanagawa, 259-1193 JapanJP
  3. 3.Center for Information Biology, National Institute of Genetics, Yata, Mishima, Shizuoka, 411-8540 JapanJP

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