ETHNIC-DIFFERENCES IN POLYMORPHISM OF AN IMMUNOGLOBULIN V(H)3 GENE

The VH26 germline gene occupies two different loci, due to gene duplic ation, and is one of the most frequently expressed human immunoglobuli n V-H genes, This report identifies the alleles of each VH26 locus and describes distinct patterns of VH26 polymorphism in three ethnic grou ps, Oligonucleotide probes targeting VH26 were used in sequence-specif ic RFLP analysis of DNA from 72 Caucasians, 52 Asians, 35 American Bla cks, and members of six families, The A locus, on a 7.0-kb TaqI band, was detected in 89% of Caucasians, 75% of Asians, and 26% of Blacks (c hi(2) = 46, P < 0.0005), The B locus, detected on a 5.0-kb band in nea rly all subjects, was found to have additional alleles occurring at 6. 8 kb in 10% of Asians and 3% of Blacks (chi(2) = 7.8, P < 0.02) and at 3.7 kb in 1.4% of Caucasians, 21% of Asians, and 9% of Blacks (chi(2) = 13.8, P < 0.001), In Asians only, the 3.7-kb hybridization band rep resented a multiple-duplication unit containing three or four gene cop ies, Duplications of other VH26 alleles, and null alleles of the B loc us, were also seen, An exact VH26 sequence was cloned from the 5.0-kb allele and likely exists in the 7.0- and 6.8-kb alleles, A novel seque nce cloned from the 3.7-kb allele differed from VH26 by nine nucleotid es and appears to have evolved by gene conversion in CDR2, The total d iploid gene dose of the A and B loci ranged from one to as many as six copies of VH26-containing genes, and from zero to as many as six to e ight copies of the 3.7-kb allele, We conclude that ethnic differences in polymorphism exist at both VH26 loci. These differences could influ ence VH26 expression because they involve variations in gene copy numb er and coding region sequence.