title: The human CD38 gene: polymorphism, CpG island, and linkage to the CD157 (BST-1) gene.
abstract: CD38 is a leukocyte activation antigen and ectoenzyme [NAD(P)+ glycohydrolase; EC 3.2.2.6] involved in numerous immune functions. The human CD38 gene is complex [eight exons, >80 kilobases (kb) long] located on Chromosome 4p15, and part of the eukaryotic NAD+ glycohydrolase/ADP-ribosyl cyclase gene family. Because of the increasing relevance of the CD38 molecule in the host immune response to infectious, tumoral, and metabolic diseases, we investigated the genetic variability and linkage of the human CD38 locus. We report that (1) the restriction endonuclease Pvu II identifies a bi-allelic polymorphism here defined as formed by the alleles CD38*A (12 kb) and CD38*B (9/2.5 kb); (2) their frequency in the healthy Italian Caucasian population is 14% and 86%, respectively; (3) the polymorphic Pvu II site is located at the 5' end of the first intron of the CD38 gene; (4) in conjunction with the polymorphic site, we identified a 900 base pair CpG island associated with the CD38 gene, with two potential Sp1 binding sites; (5) the CpG island may play a role in the regulation of CD38 expression and is hypomethylated in various cell lines; (6) by pulsed-field gel electrophoresis we show that CD38 and its paralogue, the bone-marrow stromal cell antigen BST-1 (CD157), map to the same 800 kb Avi II fragment, indicating that the two human ecto-NADase genes are closely linked.
authors.affiliation: Laboratory of Cell Biology, Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 19, I-10126 Torino, Italy. cellbiol@csi.it
authors.forename: E
authors.initials: E
authors.lastname: Ferrero
authors.forename: F
authors.initials: F
authors.lastname: Saccucci
authors.forename: F
authors.initials: F
authors.lastname: Malavasi
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D018899:CpG Islands; D019175:DNA Methylation; D015252:Deoxyribonucleases, Type II Site-Specific; D058851:GPI-Linked Proteins; D008040:Genetic Linkage; D006801:Humans; D007438:Introns; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics*; D009244:NAD+ Nucleosidase / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012689:Sequence Homology, Nucleic Acid; D044465:White People / Q000235:genetics
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009097:Multienzyme Complexes; C025630:CAGCTG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; D036541:ADP-ribosyl Cyclase; C087521:ADP-ribosyl cyclase 2; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1