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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 omega,N omega-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.

Type

Journal article

Journal

J Immunol

Publication Date

01/07/1999

Volume

163

Pages

278 - 287

Keywords

Amidohydrolases, Amino Acid Sequence, Animals, Antigens, Ly, Chloride Channels, Genes, Immunoglobulin, Genetic Markers, Humans, Hydrolases, Major Histocompatibility Complex, Mice, Microsatellite Repeats, Molecular Sequence Data, Multigene Family, Protein Isoforms, Receptors, Immunologic, Sequence Alignment, Sequence Homology, Amino Acid, Spondylitis, Ankylosing