T. Shiina et al., Genomic anatomy of a premier major histocompatibility complex paralogous region on chromosome 1q21-q22, GENOME RES, 11(5), 2001, pp. 789-802
Human chromosomes 1q21-q25, 6p21.3-22.2, 9q33-q34, and 19p13.1-p13.4 carry
clusters of paralogous loci, to date best defined by the flagship 6p MHC re
gion. They have presumably been created by two rounds of large-scale genomi
c duplications around the time of vertebrate emergence. Phylogenetically, t
he 1q21-25 region seems most closely related to the 6p21.3 MHC region, as i
t is only the MHC paralogous region that includes bona fide MHC class I gen
es, the CD1 and MR1 loci. Here, to clarify the genomic structure of this mo
del MHC paralogous region as well as to gain insight into the evolutionary
dynamics of the entire quadriplication process, a detailed analysis of a cr
itical 1.7 megabase (Mb) region was performed. To this end, a composite, de
ep, YAC, BAG, and PAC contig encompassing all five CD1 genes and linking th
e centromeric +P5 locus to the telomeric KRTC7 locus was constructed. Withi
n this contig a 1.1-Mb BAC and PAC core segment joining CD1D to FCER1A was
fully sequenced and thoroughly analyzed. This led to the mapping of a total
of 41 genes (12 expressed genes, 12 possibly expressed genes, and 17 pseud
ogenes), among which 31 were novel. The latter include 20 olfactory recepto
r (OR) genes, 9 of which are potentially expressed. Importantly, CD1, SPTA1
, OR, and FCER1A belong to multigene families, which have paralogues in the
other three regions. Furthermore, it is noteworthy that 12 of the 13 expre
ssed genes in the 1q21-q22 region around the CD1 loci are immunologically r
elevant. In addition to CD1A-E, these include SPTA1, MNDA, IFI-16, AIM2, BL
1A, FY and FCER1A. This functional convergence of structurally unrelated ge
nes is reminiscent of the 6p MHC region, and perhaps represents the emergen
ce of yet another antigen presentation gene cluster, in this case dedicated
to lipid/glycolipid antigens rather than antigen-derived peptides.