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-N-Dimethylarginine Dimethylaminohydrolase Homologue, Are Found in a 30-kb Segment of the MHC Class III Region1 ,2
*
Medical Research Council Immunochemistry Unit, Department of Biochemistry, Oxford University, Oxford, United Kingdom; and
HGMP Resource Centre, Hinxton, Cambridge, United Kingdom
Many of the genes in the class III region of the human MHC encode
proteins involved in the immune and inflammatory responses. We have
sequenced a 30-kb segment of the MHC class III region lying between the
heat shock protein 70 and TNF genes as part of a program aimed at
identifying genes that could be involved in autoimmune disease
susceptibility. The sequence analysis has revealed the localization of
seven genes, whose precise position and order is
cen-G7-G6-G6A-G6B-G6C-G6D-G6E-tel, five of which are fully encoded in
the sequence, allowing their genomic structures to be defined. Three of
them (G6C, G6D, and G6E) encode putative proteins that belong to the
Ly-6 superfamily, known to be GPI-anchored proteins attached to the
cell surface. Members of the family are specifically expressed and are
important in leukocyte maturation. A fourth gene, G6B, encodes a novel
member of the Ig superfamily containing a single Ig V-like domain and a
cytoplasmic tail with several signal transduction features. The G6 gene
encodes a regulatory nuclear chloride ion channel protein, while the
G6A gene encodes a putative homologue of the enzyme
N
,N-dimethylarginine
dimethylaminohydrolase, which is thought to be involved in regulating
nitric oxide synthesis. In addition, three microsatellite markers,
9N-1, 82-2, and D6S273 are contained within the sequence, the last two
of which have been reported to be strongly associated with the
autoimmune disease ankylosing spondylitis.
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