Five novel missense mutations of the Lewis gene (FUT3) in African (Xhosa) and Caucasian populations in South Africa

Five novel missense mutations, viz., C304 A, T370 G, G484 A, G667 A, and G808 A, in the Lewis gene (FUT3) were detected in African (Xhosa) and Caucasian individuals in South Africa. These single base substitutions may result in changes in amino acid residues from Gln102 to Lys in the 304 mutation, Ser124 to Ala in the 370 mutation, Asp162 to Asn in the 484 mutation, Gly223 to Arg in the 667 mutation, and Val270 to Met in the 808 mutation. Out of the five novel mutations identified in this investigation, four new alleles (le(484,667), le(484,667,808), Le(304), and Le(370)) were determined in the Xhosa population and two new alleles (le(202,314,484) and Le(304)) in the Caucasian population. The determination of alpha(1,3/1,4) fucosyltransferase activity, after transfection of plasmids containing the new alleles into COS7 cells, suggested that alleles le(484,667) and le(484,667,808) encoded an inactive enzyme, and that alleles Le(304) and Le(370) encoded a functional enzyme. In addition, we also examined the incidence of five common alleles, Le(59), le(59,508), le(59,1067), le(202,314), and le(1067) in two populations by the polymerase chain reaction/restriction fragment length polymorphism method and compared differences in the allele frequencies of FUT3 among three ethnic groups (Orientals, Africans, and Caucasians).