Infection-associated FUT2 (Fucosyltransferase 2) genetic variation and impact on functionality assessed by in vivo studies

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Title Infection-associated FUT2 (Fucosyltransferase 2) genetic variation and impact on functionality assessed by in vivo studies
Author Silva, Lara M.; Carvalho, Ana S.; Guillon, Patrice Michel Guy; Seixas, Susana; Azevedo, Maria; Almeida, Raquel; Ruvoën-Clouet, Nathalie; Reis, Celso A.; Pendu, Jacques Le; Rocha, Jorge; David, Leonor
Journal Name Glycoconjugate Journal
Year Published 2010
Place of publication United States
Publisher Springer
Abstract The secretor (Se)/nonsecretor (se) histo-blood group variation depends on the action of the FUT2 enzyme and has major implications for human susceptibility to infections. To characterize the functionality of FUT2 variants, we assessed the correlation between saliva phenotypes and sequence variation at the FUT2 gene in sixty seven individuals from northern Portugal. While most non-secretor haplotypes were found to carry the 428G > A nonsense mutation in association with a 739G > A missense substitution, we have also identified a recombinant haplotype carrying the 739*A allele together with the efficient 428*G variant in individuals with the Se phenotype. This finding suggested, in contrast to previous results, that the 739*A allele encodes an efficient Se allele. To test this hypothesis we evaluated the in vivo enzyme activity of full coding expression constructs in transient transfection of CHO-K1 cells using FACS (fluorescence-activated cell sorting) analysis and expression of type 2 and type 3 chain H structures as read out. We detected FUT2 activity for the 739*A expression construct, demonstrating that the 739G > A substitution is indeed not inactivating. In accordance with the hypothesis that FUT2 is under long standing balancing selection, we estimated that the time depth of FUT2 global genetic variation is as old as 3 million years. Age estimates of specific variants suggest that the 428G > A mutation occurred at least 1.87 million years ago while the 739G > A substitution is about 816,000 years old. The 385A > T missense mutation underlying the non-secretor phenotype in East Asians appears to be more recent and is likely to have occurred about 256,000 years ago.
Peer Reviewed Yes
Published Yes
Alternative URI
Volume 27
Issue Number 1
Page from 61
Page to 68
ISSN 0282-0080
Date Accessioned 2010-07-27
Language en_AU
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Host-Parasite Interactions; Immunogenetics (incl Genetic Immunology); Virology
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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