POLYMORPHISM IN THE INTERFERON-ALPHA GENE FAMILY

A pronounced genetic polymorphism of the interferon type I gene family has been assumed on the basis of RFLP analysis of the genomic region as well as the large number of sequences published compared to the num ber of loci. However, IFNA2 is the only locus that has been carefully analyzed concerning gene frequency, and only naturally occurring rare alleles have been found. We have extended the studies on a variation o f expressed sequences by studying the IFNA1, IFNA2, IFNA10, IFNA13, IF NA14, and IFNA17 genes. Genomic whiteblood-cell DNA from a population sample of blood donors and from a family material were screened by sin gle-nucleotide primer extension (allele-specific primer extension) of PCR fragments. Because of sequence similarities, in some cases ''neste d'' PCR was used, and, when applicable, restriction analysis or contro l sequencing was performed. All individuals carried the interferon-alp ha 1 and interferon-alpha 13 variants but not the LeIF D variant. At t he IFNA2 and IFNA14 loci only one sequence variant was found, while in the IFNA10 and IFNA17 groups two alleles were detected in each group. The IFNA10 and IFNA17 alleles segregated in families and showed a clo se fit to the Hardy-Weinberg equilibrium. There was a significant link age disequilibrium between IFNA10 and IFNA17 alleles. The fact that th e extent of genetic polymorphism was lower than expected suggests that a majority of the previously described gene sequences represent nonpo lymorphic rare mutants that may have arisen in tumor cell lines.