MULTIPLE ORIGINS OF THE HUMAN GLYCOPHORIN-STA GENE - IDENTIFICATION OF HOT-SPOTS FOR INDEPENDENT UNEQUAL HOMOLOGOUS RECOMBINATIONS

作者：HUANG CH; BLUMENFELD OO

来源：Journal of Biological Chemistry, 1991, 266(34): 23306-23314.

Human glycophorin St(a) (HGpSt(a)), one of the structural variants of erythrocyte membrane sialoglycoproteins, is encoded by a delta-alpha hybrid gene that arose from a single unequal crossover between the parent HGpB(delta) and HGpA(alpha) genes. We report here the identification of two new HGpSt(a) genes (type A and type B) in four unrelated St(a) heterozygotes from two ethnic groups. These St(a) genes represent distinct genetic isoforms that differ from the previously reported St(a) gene (type C) in the location of crossing-over sites. Comparison of nucleotide sequences among HGpB(delta), HGpA(alpha), and HGpSt(a) type A genes revealed that the delta-alpha unequal crossover for the St(a) type A gene occurred 110-246 base pairs downstream from pseudoexon III. In the crossing-over site of this St(a) gene, an AT-rich sequence lying 3' to a nonameric palindrome was found to be highly similar to the lambda-phage attachment site, att B, in inverted orientation. In the St(a) type B gene, the delta-alpha crossing-over point was localized to an AG-rich sequence that is 302-490 base pairs downstream from pseudoexon III. Multiple lambda-chi-like elements were identified at the crossover boundaries and within the breakpoint of this St(a) gene. These results suggest strongly that recurrent and independent unequal recombination events have occurred in the formation of multiple St(a) genes and that particular genomic sequences are important in defining the recombination sites for these homology-driven processes.

• 出版日期1991-12-5