Author:

Keywords:

Abnormalities, Multiple, Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, Chromosome Aberrations, Chromosome Deletion, Chromosome Disorders, Chromosome Mapping, Chromosomes, Human, Pair 4, Cloning, Molecular, Comparative Study, Cricetinae, DNA, Complementary, Exons, Genes, Glycoproteins, Humans, Hybrid Cells, In Situ Hybridization, Fluorescence, LDL-Receptor Related Protein-Associated Protein, Mental Retardation, Mice, Molecular Sequence Data, Research Support, Non-U.S. Gov't, Sequence Alignment, Sequence Homology, Species Specificity, Syndrome, Science & Technology, Life Sciences & Biomedicine, Biotechnology & Applied Microbiology, Genetics & Heredity, DENSITY-LIPOPROTEIN RECEPTOR, NEPHRITIS ANTIGENIC COMPLEX, ACTIVATOR INHIBITOR TYPE-1, ALPHA-2-MACROGLOBULIN RECEPTOR, HEYMANN NEPHRITIS, PLASMINOGEN-ACTIVATOR, LDL-RECEPTOR, MOLECULAR-CLONING, ALPHA(2)-MACROGLOBULIN RECEPTOR, MOUSE ALPHA-2-MACROGLOBULIN, Intellectual Disability, 0604 Genetics, 0806 Information Systems, 3105 Genetics

Abstract:

We report the molecular cloning of the human gene (symbol LRPAP1) coding for the alpha 2-macroglobulin receptor-associated protein (A2MRAP), as well as the gene coding for the 44-kDa heparin-binding protein (HBP-44), its murine counterpart. For both, genomic cosmid clones were isolated, and for the human gene a bacteriophage P1 clone containing the entire A2MRAP gene was also retrieved. The genes were characterized after subcloning: in both species, the known coding part of the cDNA is encoded by eight exons, and the position of the boundaries of the exons was conserved. The human LRPAP1 locus was assigned to chromosome 4 by PCR of human-hamster hybrid cell lines and by fluorescence in situ hybridization to band 4p16.3. This maps closely to the variable constitutional deletions of the short arm of chromosome 4, observed cytogenetically in patients with the Wolf-Hirschhorn syndrome. Metaphase spreads of two such patients were analyzed by fluorescence in situ hybridization with an LRPAP1 genomic probe. The first patient, with karyotype 46,XY,del4(p14-p16.1), had retained both copies of the LRPAP1 gene. In contrast, the other patient, with karyotype 46,XY,del4(p15.3-pter), displayed no signal for LRPAP1 on the deleted chromosome.