5 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, a nd G808 A, in the Lewis gene (FUT3) were detected in African (Xhosa) a nd Caucasian individuals in South Africa. These single base substituti ons 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 Me t in the 808 mutation. Out of the five novel mutations identified in t his 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. Th e determination of alpha(1,3/1,4) fucosyltransferase activity, after t ransfection of plasmids containing the new alleles into COS7 cells, su ggested that alleles le(484,667) and le(484,667,808) encoded an inacti ve enzyme, and that alleles Le(304) and Le(370) encoded a functional e nzyme. In addition, we also examined the incidence of five common alle les, Le(59), le(59,508), le(59,1067), le(202,314), and le(1067) in two populations by the polymerase chain reaction/restriction fragment len gth polymorphism method and compared differences in the allele frequen cies of FUT3 among three ethnic groups (Orientals, Africans, and Cauca sians).