Allelic divergence in the human insulin gene provides evidence for intragenic recombination events in the non-coding regions: evidence for existence of new alleles

Abstract

Intragenic polymorphism of the human insulin gene (INS) was investigated 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 the coding regions were the same as INS sequences previously reported, and four nucleotides, at positions +216, +1045, +1367, and +1380 in the 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 designated alpha 4 (A-C-C-A), alpha 5 (A-G-C-C), alpha 6 (A-C-T-C), and beta 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 predominant form in our sample; the new variant alleles, as well as allele beta 1, appeared to be much less frequent in INSs genes of the Korean subjects studied. Furthermore, the new alleles were detected only in heterozygous form. These results suggest that intragenic recombination can account for allelic divergence in INS.

Systematic Search for Single Nucleotide Polymorphisms in the Insulin Gene: Evidence for a High Frequency of −23T→A in Japanese Subjects

“…The allele frequency of the alpha allele, although haplotypes were not examined, is reported to be 92% in Japanese and 77% in southern Indian subjects (16,17). An alpha allele is also reported to be dominant in Korean (13). There appears to be a difference in the frequency of these alleles in the insulin gene between Asians and other ethnic groups.…”

“…The frequency of Ϫ23T 3 A is reported to be about 30% in Europeans, suggesting that Africans may have a frequency which is similar to Europeans (6). Kim et al reported that the frequency of Ϫ23T 3 A is also high (89.6%) in Korean subjects (13). In these ethnic groups, the Japanese appear to have the highest frequency of this allele, based on currently available data.…”

Interallelic recombination is probably responsible for the occurrence of a new αs1‐casein variant found in the goat species

“…Gene conversion events, which usually account for exchanges over short sequence tracts [31], have been mainly described and intensively investigated as mechanisms generating allelic diversity in highly polymorphic genetic systems, such as the loci encoding the class‐II cell surface antigens of the major histocompatibility complex in humans [32,33]. Both mechanisms have also been thought to account for genetic disorders in humans, such as sporadic Alzheimer disease cases [34] and diabetic pathology involving the gene encoding insulin [35].…”