Genetic recombination in the ABO blood group gene region

ABO基因的克隆和测序表明，孩子的ABO基因由5‘端的B等位基因序列和3’端的01等位基因序列组成(B-01阵列)。通过B等位基因序列恢复01等位基因的261G缺失，使得真实的阅读框在杂合等位基因中被重新定位，导致糖基转移酶的表达具有A1活性。对主要的四个等位基因A1、B、01和01v的广泛测序显示，外显子和内含子中都有等位基因特异序列，相同等位基因中的核苷酸存在差异。这些多态位点使我们能够在这些杂交等位基因中定义CHE重组断裂点。这些断裂点被发现位于ABO基因的不同位置。发现一个杂交等位基因有两个断裂点，一个位于Incron V(01v-B)，另一个位于外显子7(B-01v)，可能不是由基因交换引起的，而是由基因转换引起的。ABO杂合等位基因的频率似乎在种族群体中有所不同，因为我们在德国人群中没有发现杂交等位基因，在少数族裔群体中只发现了一个等位基因。

Cloning and sequencing of the ABO genes from a family where ABO inheritance had been discrepant between the child (genotype ; A01) and the father (genocype ; 101) showed that the apparent A allele in the child was composed of the B allelic sequence in the 5' portion and the 01 allelic sequence in the 3' portion (B-01 array). The recovery of the 261G deletion in the 01 allele by the B allelic sequence allowed the authentic reading frame to be res : ored in the hybrid allele, resulting in expression of glycosyltransferase with the A1 activity.Screening of a random Japanese population then reveal a relatively frequent occurrence (about 1%) of hybrid alleles wich various arrays. Extensive sequencing of the major four alleles, A1, B, 01, and 01v, showed allele-specific sequences in both exons and introns and nucleotide differences in the same alleles. These polymorphic sites enabled us to define che recombination breakpoints in those hybrid alleles. These breakpoints were found to locace variously within the ABO gene. A hybrid allele was found to have two breakpoints, one in incron V (01v-B) and the other in exon 7 (B-01v), probably resulting not from crossing-over but from gene conversion.We scudied population samples from Japanese, some minor ethnic groups in South America, and German for the occurrence of ABO hybrid alleles. The frequency of the ABO hybrid alleles seems to differ in ethnic groups because we found no hybrid alleles in a German population and only a single allele in the minor ethnic groups.