IDENTIFICATION OF A NEW PLASMA ALPHA(1,3) FUCOSYL-TRANSFERASE (FUT6) ALLELE REQUIRES AN EXTENDED GENOTYPING STRATEGY

Screening the FUT6 gene of 40 Swedish individuals, originally selected for genotyping of FUT3, revealed an unexpected high frequency of muta tions. Four were originally typed as homozygous for the enzyme lethal mutation G739A by Taq alpha I restriction pattern, but only one lacked plasma alpha(1,3)fucosyltransferase activity. Cloning and sequencing of FUT6 from 2 of them revealed a new allele, without the G739A mutati on, but with two new point mutations C738T and G977A. Segregation of t his allele was confirmed in Swedish and Indonesian families. Since G73 9A and C738T mutations are only one nucleotide apart and induce the sa me modification of Taq alpha I cleavage, a new screening strategy for FUT6 was adopted. The homozygous inactivating G739A mutation was for t he first time identified in Caucasian and Polynesian individuals, both lacking plasma enzyme activity. The mutation C370T was present in 25 of the 40 Swedish individuals and the inactivating mutation C945A was not found at all. These findings stress the dangers of transferring re striction enzyme genotype strategies from one population to another an d of inferring phenotypes from genotypes without phenotyping and/or pe rforming confirmatory cloning and sequencing.