Human immunoglobulin variable region genes: a new VH sequence used to detect polymorphism.

A human heavy chain variable region subgroup III pseudogene (HV3.3) was isolated, characterized, and sequenced. When HV3.3 was hybridized to Southern blots of human DNA, two potentially informative polymorphic bands, resulting from 2.7 kb Hind III (HH2.7) and 7.3 kb Eco RI (HE7.3) fragments, were detected with frequencies of 0.553 and 0.606, respectively. These polymorphic bands showed Mendelian segregation in families and appeared to be in tight linkage disequilibrium with each other (chi 2(1) = 24.91, P less than 0.001). Evidence from sibling-pair data indicated linkage of the Hind III polymorphic band to constant region allotypic and restriction fragment length polymorphism markers. Bands representing alternative forms of the polymorphic restriction sites were not detected for either HH2.7 or HE7.3. This indicates either that the alternative fragments comigrate with homologous fragments resulting from conserved restriction sites, or that the polymorphism is due to a gene duplication or deletion. No band segregating with HH2.7 was found in separate digests using eight other enzymes. Although this indicates that a major deletion or unlikely, it does not exclude the possibility of a gene deletion or duplication affecting the intergenic region(s) of one or more homologous genes. Whatever the precise explanation, these findings support the hypothesis that there is polymorphic variation of VH gene repertoires in man.