Ethnic differences of polymorphism of an immunoglobulin VH3 gene.

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Abstract

The VH26 germline gene occupies two different loci, due to gene duplication, and is one of the most frequently expressed human immunoglobulin VH 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 (chi2 = 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 (chi2 = 7.8, P < 0.02) and at 3.7 kb in 1.4% of Caucasians, 21% of Asians, and (9% of Blacks (chi2 = 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 mull 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.

Authors

E H Sasso, J H Buckner, L A Suzuki