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Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, United Kingdom
It is becoming increasingly apparent that many of the genes in the
class III region of the human MHC encode proteins involved in the
immune and inflammatory responses. Furthermore, genetic studies have
indicated that genes within the class III region, particularly the
telomeric segment containing the TNF gene, could contribute to
susceptibility to diseases of immune-related etiology. We have
sequenced an 82-kb segment of DNA around the TNF gene to identify
candidate disease susceptibility genes in this region. The 10 known
genes in this region have been precisely positioned with the order
allograft inflammatory factor 1, G1, 1C7, leukocyte-specific
transcript 1 (B144), lymphotoxin B, TNF, lymphotoxin
A, NB6, IKBL, BAT1 (centromere to telomere), and their genomic
structures have been defined. Comparison of the G1 genomic region with
previously described cDNA and genomic sequences, together with the
results of reverse transcriptase-PCR, indicates that three alternative
transcripts, G1, allograft inflammatory factor 1, and
IFN-
-responsive transcript, are all derived from this gene. The
completion of the sequence of 1C7 (D6S2570) has revealed that this gene
encodes a putative novel member of the Ig superfamily. A number of
alternatively spliced transcripts of 1C7 were identified by reverse
transcriptase-PCR, all of which are expressed in immune-related cell
lines. Alternative splicing within the Ig domain-encoding region was
seen to result in possible set switching between an IgV domain and an
IgC2 domain. Lastly, a previously unidentified gene, homologous to a
number of V-ATPase G subunits, has been located 1 kb telomeric of
IKBL.
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