Molecular Analysis of the HLA Gene Region by Large DNA Cloning

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In order to clarify structural organization of the human histocompatibility region, (HLA) we aimed to clone the whole HLA region encompassing 3, 500kb by cosmid and YAC cloning. In this year, we have established the YAC cloning system and could obtained the additional 1, 450kb region mainly encoding the HLA class I region. These region, especially around the HLA-B and -C genes, was found to contains numerous CpG islands which indicate the presence of new expressed gene. Isolation and characterization of CDNA clones from these new genes are under way to pursuit the possibility that they are responsible for the susceptibility to some HLA class I -associated diseases such as Behcet disease, multiple sclerosis, psoriasis vulgaris et al.We have also gene-walked in the 250kb region to the centromeric side from the class III region, which should represent the genetic boundary between the GC rich and AT rich - region. Analysis of the cosmid DNAs from this region indicated that the GC rich to AT rich change occurred discontinuously, but not successively. During the course of this experiment a new gene encoding the tenascin-like protein was identified. This gene contained the fibronection III and EGF repeats with the fibrinogen-like domain and was mainly expressed in the lymphoid cells. Correlation of this new gene with a lot of the HLA- class 11 associated diseases will be investigated to understand the function of this gene.