Variable genes

Phase and antigenic variation in bacteria. These may be mediated by slipped-strand mispairing of repeat sequences that occur in these phase variable genes or by gene duplication events. 

Some investigators raised questions challenging housekeeping genes or proteins that were recommended as internal controls due to the variable gene/ protein expression that exists in various tissue or organs.35,36... 

Higher rates of horizontal gene exchange, based on the abundant presence of plasmid transfer (Tra), plasmid mobilization (Mob), transposons (Tn), insertion seqnences (IS), and similar fnnctions or elements, seem to be a rule in these variable gene pools. 

Schroeder, H.W., Wang, J.Y. (1990). Preferential utilization of conserved immunoglobulin heavy chain variable gene segments during human fetal life. Proc. Natl. Acad. Sci. USA, 87, 6146-6150. 

Hazzalin CA, Mahadevan LC. 2002. MAPK-regulated transcription A continuously variable gene switch Nat Rev Mol Cell Biol. 3 30-40. 

Gearhart, P.J. Bogenhagen, D.F. (1983). Clusters of point mutations are found exclusively around rearranged antibody variable genes. Proc. Natl. Acad. Sci. USA 80, 3439-3443. 

Gorski, J., Rollini, P., Mach, B. (1983). Somatic mutations of immunoglobulin variable genes are restricted to the rearranged V gene. Science 220, 1179-1181. 

Kindt, T.J., Gris, C., Guenet, J.L., Bonhomme, F., Cazenave, P.-A. (1985). Lambda light chain constant and variable gene complements in wild-derived inbred mouse strains. Eur. J. Immunol. 15,... 

Kirschbaum, T., Jaenichen, R., Zachau, H.G. (1996). The mouse immunoglobulin K locus contains about 140 variable gene segments. Eur. J. Immunol. 26, 1613-1620. 

Schable, K.F. Zachau, H.G. (1993). The variable genes of the human immunoglobulin k locus. Biol. Chem. Hoppe-Seyler 374,1001-1022. 

Taki, S., Meiering, M., Rajewsky, R. (1993). Targeted insertion of a variable gene locus into the immunoglobulin heavy chain locus. Science 262, 1268-1271. 

Marks JD, Tristem, Karpas A, Winter G, Oligonucleotide primers for polymerase chain reaction amplification of human immunoglobulin variable genes and design of family-specific oligonucleotide probes, Eur. J. Immunol., 21 985-991, 1991. 

These data show that there can be great complexity even if we deal with a single variable gene as in traditional pharmacogenetics. It is a relatively simple process to count the absence of enzyme activity ( the poor metabolizer phenotype ) in one population, but data thus obtained, for instance, in Europe, may be useless everywhere else. 

Figure 3.4 A possible scheme for IgE transcription in which the genes for other immunoglobulins are looped out to leave the IgE transcript next to the variable gene transcript.

Green LL, Jakobovits A Regulation of B cell development by variable gene complexity in mice reconstituted with human immunoglobulin yeast artificial chromosomes. J Exp Med 1998 188 483 195. 

CD5+ B lymphocytes. Lymphocytes of type Bl-a, which are predominant in fetal lymphoid organs and in neonatal cord blood. In adults, these cells range from 2% to 6% of total mononuclear cells in peripheral blood. They utilize an immunoglobulin variable gene repertoire different from that of CD5 B cells and produce natural autoantibodies. The expansion of autoreactive Bl-a cells has been reported in peripheral blood of patients with autoimmune diseases (e.g. rheumatoid arthritis, Sjogren syndrome, antiphospholipid syndrome). In rheumatoid arthritis, these cells can account for up to 60% of circulating B cells and may produce rheumatoid factor. The pathological relevance of these observations is unclear, however. 

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