VARIABILITY OF THE IMMUNOGLOBULIN HEAVY-CHAIN CONSTANT-REGION LOCUS -A POPULATION STUDY

The Immunoglobulin Heavy chain Constant region (IGHC) locus is a multi gene family composed of highly homologous segments often involved in u nequal crossings over that lead to deleted and duplicated haplotypes. The frequencies of these haplotypes in 558 individuals from Lombardy, Veneto, Puglia and Sardinia were determined by Pulsed Field Gel Electr ophoresis (PFGE), followed by Southern blotting with four IGHC probes, and compared with those observed in 110 subjects from Piedmont. Twent y deletions and 60 duplications were characterized, all in heterozygou s individuals except for 2 homozygous deletions. The differences in fr equency between the five populations were not significant. The deletio ns/duplications involved one or more genes: GP-A2, A1-E and G4 duplica tions, and A1-E and GP-A2 deletions were the most common. Four new dup lications are described: three, involving the genes from GP to A2, fro m G2 to G4, and G4, are counterparts of known deletions. The fourth du plication spans from GP to G2. A G1 deleted heterozygous individual ne ver previously described in Italy is reported. All the rearranged hapl otypes seem to be the result of unequal crossing over. The difference between the number of duplications and deletions was significant in Sa rdinia, Lombardy, Puglia and in the total of 668 subjects (P < 0.001). This may be due to se lection or genetic drift.