Identification of the Dombrock blood group glycoprotein as a polymorphic member of the ADP-ribosyltransferase gene family

Identification of the 25 known human blood group molecules Is of fundamenta l importance for the fields of erythroid cell biology and transfusion medic ine. Here we provide the first molecular description of the "Dombrock" bloo d group system. A candidate gene was identified by in silico analyses of ap proximately 5000 expressed sequence tags (ESTs) from terminally differentia ting human erythroid cells. Transfection experiments demonstrated specific binding of anti-Dombrock and confirmed glycosylphosphatidylinositol membran e attachment. Dombrock expression is developmentally regulated during eryth roid differentiation and occurs at highest levels in the fetal liver Homolo gy studies suggest that the Dombrock molecule is a member of the adenosine 5'-diphosphate (ADP)-ribosyltransferase ectoenzyme gene family. Genotypic c omparisons suggest Do(a) versus Do(b) antigenicity results from a single am ino acid substitution within an encoded arginine-glycine-aspartic acid (RGD ) motif of the molecule. (Blood. 2000;96: 2621-2627) (C) 2000 by The Americ an Society of Hematology.