Structure of the human amyloid-precursor-like protein gene APLP1 at 19q13.1

Abstract

Amyloid-precursor-like protein 1 (APLP1) is a membrane-associated glycoprotein, whose gene is homologous to the APP gene, which has been shown to be involved in the pathogenesis of Alzheimer's disease. APLP1 is predominantly expressed in brain, particularly in the cerebral cortex postsynaptic density. The genomic organization of mouse APLP1 has been determined, and the human gene has been mapped to chromosomal region 19q13.1. In the present study, the entire sequence of human APLP1 has been determined from a cosmid clone, and the genomic structure has been determined. The gene is 11.8 kb long and contains 17 exons. We have previously mapped the gene for congenital nephrotic syndrome (CNF) to the APLP1 region, to the vicinity of marker D19S610 located between markers D19S191 and DS19608. APLP1 is the only known gene in the vicinity of the marker D19S610. Because of its location and the proposed interference of amyloid with basement membrane assembly, APLP1 has been considered a candidate gene for CNF. All exon regions of the gene were amplified by the polymerase chain reaction and sequenced from DNA of CNF patients. No differences were observed between CNF patients and controls, suggesting that mutations in APLP1 are not involved in the etiology of CNF.