THE KELL BLOOD-GROUP SYSTEM

The Kell blood group system is complex containing over 20 different an tigens. Some of the Kell antigens may be organized in 5 sets of paired alleles with opposing high and low incidence antigens while others ar e independently expressed. Molecular cloning established that Kell ant igens are carried on a 93kDa, type II, membrane glycoprotein. The Kell gene (KEL) is located at 7q 32-36 and spans about 21,5 kb. The coding sequence is organized in 19 exons. The promoter region does not conta in TATA sequences but has possible transcription binding sites for GAT A-1 and Spl. Kell protein shares a putative enzymatic active amino aci d sequence with a large family of zinc endopeptidases and has closest structural and sequence homology with neutral endopeptidase 24,11 (a.k .a. enkephalinase, CALLA) and endothelin converting enzyme (ECE-1). Th e molecular basis of several important Kell antigens has been determin ed and all are due to base substitutions causing single amino acid cha nges. The K1/K2 polymorphism is due to a C to T substitution in exon 6 , encoding a threonine to methionine change. This mutation disrupts an N-glycosylation site. Two PCR-based methods,, including use of allele -specific primers, have been developed which may be used to determine fetal K1/K2 genotypes. These tests can potentially identify those preg nancies at risk for hemolytic disease of the newborn. The allelic rela tionship of Kp(a), Kp(b) and KPc was confirmed, since single base subs titutions in the same codon encode 3 different amino acids. As compare d to Js(b) (K7), Js(a) (K6) phenotypes have 2 different base substitut ions in exon 17. One substitution, T 1910 C, results in an amino acid change (Leu 597 Pro) and the other is a silent mutation. Ul(a) (K10), which may be independently expressed, also has a single base substitut ion (exon 13, A 1601 T) and encodes GLu 496 Val. Distinctive RFLP patt erns for different phenotypes allow genotyping in the Kell blood group system.