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

The VH26 germline gene occupies two different loci, due to gene duplication, and is one of the most frequently expressed human immunoglobulin V-H genes, This report identifies the alleles of each VH26 locus and describes distinct patterns of VH26 polymorphism in three ethnic groups, Oligonucleotide probes targeting VH26 were used in sequence-specific RFLP analysis of DNA from 72 Caucasians, 52 Asians, 35 American Blacks, 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 (chi(2) = 46, P < 0.0005), The B locus, detected on a 5.0-kb band in nearly 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 represented a multiple-duplication unit containing three or four gene copies, Duplications of other VH26 alleles, and null alleles of the B locus, 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 sequence cloned from the 3.7-kb allele differed from VH26 by nine nucleotides and appears to have evolved by gene conversion in CDR2, The total diploid 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 eight copies of the 3.7-kb allele, We conclude that ethnic differences in polymorphism exist at both VH26 loci. These differences could influence VH26 expression because they involve variations in gene copy number and coding region sequence.