Identification of the Kna/Knb polymorphism and a method for Knops genotyping

Abstract

BACKGROUND: DNA mutations resulting in the McCoy and Swain-Langley polymorphisms have been identified on complement receptor 1 (CR1)—a ligand for rosetting of Plasmodium falciparum-infected RBCs. The molecular identification of the Kn(a)/Kn(b) polymorphism was sought to develop a genotyping method for use in the study of the Knops blood group and malaria. STUDY DESIGN AND METHODS: CR1 deletion constructs were used in inhibition studies of anti-Kn(a). PCR amplification of Exon 29 was followed by DNA sequencing. A PCR-RFLP was developed with NdeI, BsmI, and MfeI for the detection of Kn(a)/Kn(b), McC(a)/McC(b), and Sl1/Sl2, respectively. Knops phenotypes were determined with standard serologic techniques. RESULTS: A total of 310 Malian persons were phenotyped for Kn(a) with 200 (64%) Kn(a+) and 110 (36%) Kn(a−). Many of the Kn(a−) exhibited the Knops-null phenotype, that is, Helgeson. The Kn(a/b) DNA polymorphism was identified as a V1561M mutation with allele frequencies of Kn(a) (V1561) 0.9 and Kn(b) (M1561) 0.1. CONCLUSION: The high frequency (18%) of Kn(b) in West African persons suggests that it is not solely a Caucasian trait. Furthermore, because of the high incidence of heterozygosity as well as amorphs, accurate Knops typing of donors of African descent is best accomplished by a combination of molecular and serologic techniques