Gene: [IGH/14q3233] immunoglobulin, heavy subunit, CON-J-DIV-VAR minigenes; (@IGHC @IGHDIV @IGHJ @IGHV)
|
SUM |
[1] Loci coding for the proteins of the extensive immunoglobulin family
are characterized by the most complex structure that reflects
extremely variable (with respect to amino acid sequence) structure of
the proteins themselves. One of the higher levels of the Ig molecule
structural hierarchy is represented by the tetrameric organization of
two heavy (H) and two light (L) subunits. This level has a variety of
types of H- (alpha, gamma, delta, epsilon, and mu) and L- (kappa= K
and lambda= L) polypeptides. Some types, in turn, are subdivided: two
subtypes of H-alpha and four ones of H-gamma peptides are known.
[2] The monomeric level itself is complex, too, due to subdividing the polypeptide into the 'constant' (CON) and the 'variable' (VAR) regions. These regions are encoded by the respective CON and VAR genes. As far as CON gene is concerned, the next (exon/intron) level of structural subdivision is the final one (in terms of the principal hierarchic levels); however in the case of VAR region, one more intermediate subdivision level exists, the subdivision into the 'deletion-junctional' (DY and J) regions and the 'variable' (VH, VK, and VL) monomer regions per se. DY, J, and V minigenes are presented in multiple copies. [3] This multiplicity of copies reflects the process of repeated duplications of a small number of ancestral nucleotide sequences, which have undergone numerous recombinations, convertions, and mutations in the course of evolution. Ac a result, all these copies appear to be highly homologous and is subdivided into homology groups, within which the similarity is usually greater than that between different groups. Along with a great number of coding VAR minigenes, many pseudogenes are encountered (they are usually the processed, i.e. deprived of introns, minigenes, evolving via the reverse insertions of the cDNA copies of the processed RNA transcripts into genome). In some cases (e.g., H-VAR minigenes) individual groups of homologous sequences form tandem clusters, in other cases (e.g., L-kappa VAR minigenes, VK minigenes) segments from different homology groups are lumped in one cluster. As a rule, CON and VAR minigenes are tightly linked in a small chromosomal subsegment within one large cluster. Individual VAR pseudogenes are also found outside the major cluster, sometimes in other chromosomes. [4] According to the most recent data (ref:Berman-1988), the complex locus IGH is spread on about 2.5 Mb in 14q32.33 and, in addition to ten CON genes, contains 100-200 VAR minigenes (both coding ones and pseudogenes); an approximate physical map of this regionis like this (summarized from a number of reports): SpeI-- 90 kb --SpeI |
|
REL |
FAM:IGK/02p12; FAM:IGLCJ/22q1121; FAM:IMM/00.0 |
|
REF |
PHE,FOG,POL "Chaabani &: AJHG, 37, 1164-1171, 1985 LOC,CYG,LIN,POL "Chapuis-Cellier &: J Immunogenet, 8, 257-262, 1981 LOC,CYG,LIN,POL "Cox &: Nature, 297, 428-430, 1982 PHE,FOG,POL "Curtain &: AJHG, 24, 145-155, 1972 REV "Early, Hood: Cell, 24, N1, 1-3, 1981 REV "Ellison JW, Hood: Adv Hum Genet, 13, 113-147, 1983 SEQ,MAF,EXP,ENG "Flanagan JG, Rabbitts: Nature, 300, (23 Dec), 709-713, 1982 LOC,CYG,LIN,POL "Gedde-Dahl &: Ann Hum Genet, 39, 43-50, 1975 LOC,CYG,LIN,POL "Gedde-Dahl &: Ann Hum Genet, 35, 393-400, 1972 LOC,CYG,LIN,POL "Groce &: PNAS, 76, 3416-3419, 1979 LOC,CYG,LIN,POL "Hobart MJ &: Ann Hum Genet, 45, 331-335, 1981 PHE,FOG,POL "Jazwinska EC &: AJHG, 43, 175-181, 1988 PAT,MUT "Korsmeyer &: PNAS, 78, N11, 7096-7100, 1981 PHE,FOG,POL "Kunkel &: Nature, 223, 1247-1248, 1969 PHE,FOG,POL "Lefranc MP, Rabbitts: NAR, 12, 1303-1311, 1984 PAT,MUT "Lefranc MP &: Mol Biol Med, 1, 207-217, 1983 PAT,MUT "Lefranc MP &: Nature, 300, (23/30 Dec), 760-762, 1982 SEQ,MAF,EXP,ENG "Maeda &: Cell, 45, (11 Apr), 25-33, 1986 LOC,CYG,LIN,POL "Migone N &: AJHG, 37, 1146-1163, 1985 PAT,MUT "Migone N &: PNAS, 81, 5811-5815, 1984 REV "Nossal GJV: New Engl J Med, 316, N21, 1320-1325, 1987 SEQ,MAF,EXP,ENG "Rabbitts TH &: NAR, 9, 4509-4524, 1981a SEQ,MAF,EXP,ENG "Rabbitts TH &: Cold Spring Harbor Symp, 45, (Pt 2), 867-878, 1981b REV "Roth S: Quart Rev Biol, 60, N2, 145-153, 1985 LOC,CYG,LIN,POL "Shander &: Transplant Proc, 12, N3, 417-420, 1980 LOC,CYG,LIN,POL "Smith &: Eur J Immunol, 11, 852-855, 1981 LOC,CYG,LIN,POL "Solomon &: CCG, 32, (HGM6), 319, 1982 PAT,MUT "van Dongen &: Blood, 64, N2, 571-575, 1984 PHE,FOG,POL "van Loghem, Biewenga: Mol Immunol, 20, N9, 1001-1007, 1983 PHE,FOG,POL "van Loghem &: Ann Hum Genet, 33, 351-359, 1970 PAT,MUT "Weiss &: Hum Pathol, 17, 1009-1014, 1986 PHE,FOG,POL "Zelaschi &: PNAS, 80, (Jun), 3762-3766, 1983 |
