Background: Genes for fucosyltransferases 1 (FUT1:H), 2 (FUT2:Secretor), and 3 (FUT3:Lewis) encode enzymes crucial for ABH and Lewis blood group antigen synthesis. They are highly polymorphic and ethnically and geographically specific.
Study design and methods: Genetic variations and allele frequencies of FUT1, FUT2, and FUT3 encoding regions and flanking sequences were analyzed in 100 Styrian blood donors by systematic sequencing. Haplotypes were verified with sequence-specific primers. To identify discrepancies, serologically determined ABO and Lewis blood groups were correlated to respective genotypes.
Results: Two novel FUT1 alleles were defined by 9C>T (silent) and 991C>A (P331T) mutations, the latter located in the catalytic domain of the enzyme. Five new alleles of FUT2 were found: three were characterized by new variants and two resulted from new combinations of known polymorphisms. The new 412G>A (G138S) mutation also is located in the catalytic domain. A new nonsecretor allele, based on the presence of 428G>A (nonsense), was found. Another FUT2 allele may have resulted from an intragenic crossover event. FUT3 analysis revealed seven novel alleles, partly based on the new mutations 41G>A (R14H), 1060C>G (R354G), 735G>C (silent), and 882C>T (silent). While 41G>A is placed in the cytoplasmic domain and functional, 1060C>G is placed in the catalytic domain.
Conclusion: Multiple common and sporadic sequence variations including 14 new alleles at FUT1, FUT2, and FUT3 loci were identified. Four novel mutations result in amino acid substitution in the protein. Three of them are predicted to have adverse effects on the enzyme activity. A novel nonsecretor allele was found.