Genomic Organization Around the Centromeric End of the HLA Class I Region: Large-Scale Sequence Analysis |
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Authors: | Masaaki Yamazaki Yoshio Tateno Hidetoshi Inoko |
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Institution: | (1) BioScience Research Laboratory, Fujiya Co., Ltd., 228 Soya, Hadano, Kanagawa, 257-0031 Japan, JP;(2) Division of Molecular Life Sciences, Department of Genetic Information, School of Medicine, Tokai University, Boseidai, Isehara, Kanagawa, 259-1193 Japan, JP;(3) Center for Information Biology, National Institute of Genetics, Yata, Mishima, Shizuoka, 411-8540 Japan, JP |
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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.
Received: 16 June 1998 / Accepted: 18 August 1998 |
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Keywords: | : HLA class I — Genome duplication — LINE — Gene hunting — Genome evolution |
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