ALLELIC DIVERGENCE IN THE HUMAN INSULIN GENE PROVIDES EVIDENCE FOR INTRAGENIC RECOMBINATION EVENTS IN THE NON CODING REGIONS - EVIDENCE FOREXISTENCE OF NEW ALLELES

Intragenic polymorphism of the human insulin gene (INS) was investigat ed in Korean subjects. The 1.9 kb INS sequence, including the 5' to 3' flanking regions, was amplified using the polymerase chain reaction ( PCR), and analyzed by direct sequencing. All nucleotide sequences in t he coding regions were the same as INS sequences previously reported, and four nucleotides, at positions +216, +1045, +1367, and +1380 in th e non-coding regions, were found to be polymorphic. In addition to the previously identified polymorphic alleles alpha 1 (A-C-C-C) and beta 1 (T-G-T-A), new nucleotide arrangements were also identified and desi gnated alpha 4 (A-C-C-A), alpha 5 (A-G-C-C), alpha 6 (A-C-T-C), and be ta 2 (T-C-C-C). It was concluded that the new alleles may originate by intragenic recombination within INS during chromosomal crossing-over between the alpha 1 and beta 1 alleles. The allele alpha 1 was the pre dominant form in our sample; the new variant alleles, as well as allel e beta 1, appeared to be much less frequent in INSs genes of the Korea n subjects studied. Furthermore, the new alleles were detected only in heterozygous form. These results suggest that intragenic recombinatio n can account for allelic divergence in INS.