Systematic sequence analysis of the human fucosyltransferase 2 (FUT2) gene identifies novel sequence variations and alleles

Abstract

This study identified 18 sequence variations in the FUT2 gene, and 6 were novel. The frequencies of alleles and genotypes were also determined in Chinese and Caucasian persons.

Genetic Susceptibility to Norovirus GII.3 and GII.4 Infections in Chinese Pediatric Diarrheal Disease

“…FUT2 encodes an alpha(1,2)fucosyltransferase which is responsible for the synthesis of H antigen and individuals with H antigen expressions are considered secretor positive. This gene has a significant polymorphism with ethnic specificity and several single nucleotide polymorphisms (SNP) in the FUT2 locus have been reported (17, 18). A missense mutation at nucleotide 385 (A>T) is found commonly in Asian populations (17) and homozygous carriers of this mutation are considered weak secretors, leading to low levels of ABH antigens.…”

ABO, H, and Lewis Systems

“…Many other inactive (non -secretor) alleles containing nonsense mutations have been found, some of which are listed in (Table 2.7 ) [83,84,89] . An allele with a single base deletion (778delC) was found in two of 101 black South Africans (Xhosa) [82] .…”

Carbohydrate Blood Groups

“…By analyzing the sequences of many eukaryotic and prokaryotic (α1-2)fucosyltransferases, three highly conserved sequence motifs were identifi ed. [73][74][75][76][77] In other individuals, normally functioning genes are found that contain only missense mutations (eg, Se 2 , Se 3 , Se 4 ) or combinations of silent and missense mutations (eg, Se 6 and Se 7 ). Following cloning of Se, 12,70 multiple functional and nonfunctional variants were described.…”

“…69 Motifs I, II, and III encompass amino acid residues 184-204, 226-239, and 278-288, respectively; Motif I may be responsible for binding the nucleotide sugar substrate, GDPfucose, required for the catalytic action of this enzyme. 76,77 In addition, the Se w mutant encodes a functional, but signifi cantly less active, enzyme. For example, many individuals have a normally functioning variant, Se 1 , which contains a silent mutation: 357 c → t (Table 6-7).…”

“…[122][123][124][125][126] Thus, mutating the sequence of Fuc-TIII at residues 111 and 112 to that which is found in the (α1-3)fucosyltransferase Fuc-TVI (ie, from WD in Fuc-TIII to RE in Fuc-TVI), signifi cantly improves its ability to use Type 2 chains as substrates. In these individuals the Le gene is normal but the Se (Fuc-TII) enzyme is partially defective due to a variant allele (Se w ) containing the 129 I → F mutation 74,[77][78][79] (Table 6-7). 69,97 As such, there are two highly conserved sequence motifs: Motif I comprising amino acids 152-171 and Motif II comprising amino acids 239-272.…”