Kudo S, Chagnovich D, Rearden A, Mattei M G, Fukuda M
La Jolla Cancer Research Foundation, Cancer Research Center, California 92037.
J Biol Chem. 1990 Aug 15;265(23):13825-9.
The genomic structure of a human glycophorin variant, Miltenberger class V-like molecule (MiV*), was examined. Southern blot analysis of total genomic DNA revealed that the 5' half of the MiV* gene derived from glycophorin A (GPA) gene whereas the 3' half derived from glycophorin B (GPB) gene. This structure is reciprocal to another glycophorin variant, Sta, which has a GPB-GPA hybrid structure. The genomic sequences around the crossing-over point were amplified by polymerase chain reaction, and the sequences were determined. Comparison of the nucleotide sequences of the GPA, GPB, and MiV* genes indicates that the crossing-over point is located in the region around the 3' end of intron 3 of the GPA gene. This place is different from the crossing-over point for Sta, which was found to be highly homologous to that for haptoglobin-related genes. However, the nucleotide sequences within the presumptive crossing-over point for the MiV* gene were found to be homologous in a reverse orientation to the crossing-over point proposed for haptoglobin-related genes. These results suggest strongly that homologous recombination through unequal crossing over can be facilitated by specific genomic elements such as those in common for formation of MiV*, Sta, and haptoglobin-related genes. The present study also localized the gene of the third glycophorin, GPE, at chromosome 4, q31.1 band, the same locus as for the GPA and GPB genes. The results indicate that GPE was not involved in generating MiV* or Sta hybrid gene despite the fact that it is localized adjacent to the GPA and GPB genes.
对一种人类血型糖蛋白变体米尔滕贝格V类分子（MiV*）的基因组结构进行了检测。对总基因组DNA进行的Southern印迹分析显示，MiV基因的5'端一半源自血型糖蛋白A（GPA）基因，而3'端一半源自血型糖蛋白B（GPB）基因。这种结构与另一种血型糖蛋白变体Sta相反，Sta具有GPB - GPA杂交结构。通过聚合酶链反应扩增了交叉点周围的基因组序列，并对序列进行了测定。对GPA、GPB和MiV基因的核苷酸序列进行比较表明，交叉点位于GPA基因内含子3的3'端周围区域。这个位置与Sta的交叉点不同，Sta的交叉点被发现与触珠蛋白相关基因的交叉点高度同源。然而，发现MiV基因假定交叉点内的核苷酸序列与为触珠蛋白相关基因提出的交叉点呈反向同源。这些结果有力地表明，通过不等交换进行的同源重组可以由特定的基因组元件促进，例如那些在MiV、Sta和触珠蛋白相关基因形成中常见的元件。本研究还将第三种血型糖蛋白GPE的基因定位在4号染色体q31.1带，与GPA和GPB基因相同的位点。结果表明，尽管GPE定位于GPA和GPB基因附近，但它并未参与产生MiV*或Sta杂交基因。
