DNA sequencing and screening for point mutations in the human Lewis (FUT3) gene enables molecular genotyping of the human Lewis blood group system

The human Lewis gene encodes an a(1,3/1,4)-fucosyltransferase responsible for synthesis of the Le(a) and Le(b) antigens. To define the molecular background for non-functional Lewis genes we have sequenced PCR-amplified DNA fragments from two Le(a-b-) individuals. One was homozygously mutated at nucleotides 202(T-->C) and 314(C-->T), altering Trp(68) to Arg and Thr(105) to Met, and the other was homozygously mutated at nucleotides 59(T-->G) and 1067(T-A), altering Leu(20) to Arg and Ile(356) to Lys. Using PCR we screened for these and additionally one other mutation at nucleotide 508(G-->A) among 40 Caucasians. Of 15 Le(a-b-) individuals, 7 typed as le(59/1067)le(202/314), 4 as le(202/314)le(202/314) and 1 as le(59/1067)le(59/1067). Of 21 Le(a-b+) and 4 Le(a+b-), 17 typed as LeLe and 7 as Lele(202/314). A pedigree study of 8 Lewis-positive individuals showed that the mutations at nucleotides 202 and 314 were located on the same allele.