Identification of Interferon-α7,-α14,and -α21 Variants in the Genome of a Large Human Population

Abstract

The genes for type I interferon (IFN), which include 14 IFN-α genes, 1 IFN-β gene, 1 IFN-ω gene, and a number of IKN-ω pseudogenes, are clustered on human chromosome 9. Among IFN-α genes, a number of variants have been reported. Three variants of IFN-α7 (IFN-a7a, IFN-α7b, and IFN-α7c) and IFN-αl4 (IFN-αl4a, IFN-αl4b, and IFN-αl4c) and two variants of IFN-α21 (IFN-α21a and IFN-α21b) are identified. The variants differ from each other by base changes in the coding region and can be distinguished by selective restriction enzyme analysis and DNA sequencing. We have used polymerase chain reaction (PCR) with IFN species-specific oligonucleotide primers for amplification of IFN-α7, IFN-αl4, and IFN-α21 gene sequences. Genomic DNA obtained from over 28,000 normal healthy individuals were collected in six pools for PCR amplification. To identify the presence of variant sequences, the resulting PCR products of specific IFN-α genes were analyzed by restriction endonuclease digestion and DNA sequencing, with a limit of detection of minor components to 1% and 10%, respectively. The results show that only one variant form for each of IFN-α7, IFN-αl4, and IFN-α21, namely, IFN-α7a, IFN-αl4c, and IFN-α21b, is detectable in the genomic DNA of the population examined. Similar results were obtained from the analysis of a human myeloblastoid cell line, KG-1.