Genomic organization of the human cholesterol-responsive ABC transporter ABCA7: Tandem linkage with the minor histocompatibility antigen HA-1 gene

We have recently cloned a novel cholesterol-responsive ABC transporter, des ignated ABCA7, which is predominantly expressed in human leukocytes. Here w e report the structure of the human ABCA7 gene. The ABCA7 gene spans a regi on of similar to 32 kb and comprises 46 exons. Its putative promoter sequen ce contains potential binding sites for transcription factors with roles in hematopoiesis and cholesterol metabolism. Surprisingly, sequence analysis of the ABCA7 3' gene flanking region revealed that the terminal exon of ABC A7 borders immediately on the 5' end of the coding region of the recently i dentified human minor histocompatibility antigen HA-1. We demonstrate that the coding regions of ABCA7 and HA-1 are physically separated by a 1.7-kb i ntergene region. Subsequent genomic structure analysis showed that the HA-1 gene consists of 23 exons which extend across a 16-kb genomic region. Our results provide evidence that the genes for the human minor histocompatibil ity antigen HA-1 and the ABC transporter ABCA7 are arranged in a head-to-ta il array and that both genes localize to a common locus of similar to 48 kb size on chromosome 19p13.3. (C) 2000 Academic Press.