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Selected Publication:
Matzhold, E.
Moleculargenetic analysis of the genes of fucosyltransferase 1, 2 and 3 in Styrian blood donors
[ Dissertation ] Medical University of Graz; 2010. pp. 38
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- Authors Med Uni Graz:
- Matzhold Eva-Maria
- Advisor:
- Helmberg Wolfgang
- Renner Wilfried
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- Abstract:
- 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 geografically specific. The aim of the present study was to investigate the genetic variations in Styrian blood donors. 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. Three novel FUT2 alleles were detected, characterized by new base substitutions. One of which, 412G>A, also is located in the catalytic domain. Further, the uncommon arrangement of previously known single-nucleotide-polymorphisms produced a new nonsecretor allele. Another newly identified FUT2 allele may result from an intragenic crossover event between the two most prevalent FUT2 alleles. 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 translated protein. Three of them are predicted to have adverse effects on the enzyme activity. A novel nonsecretor allele containing 428G>A was found. As reported for other populations, our data confirm the heterogeneity of fucosyltransferase genes for the Styrian population and may enhance the growing database of blood group antigen gene polymorphisms.