Molecular Cloning of a Human Genomic Region Containing the H Blood Group α(1,2)Fucosyltransferase Gene and Two H Locus-related DNA Restriction Fragments

Abstract

We have used the human H blood group alpha(1,2)fucosyltransferase (FUT1) cDNA to screen chromosome 19 cosmid libraries in a search for the human Secretor (Se) blood group gene (FUT2). One cosmid has been isolated that contains two distinct segments that cross-hybridize with FUT1. We have assembled a 100-kilobase (kb) cosmid contig, localized to 19q13.3, encompassing FUT1 and the two FUT1-related sequences, termed Sec1 and Sec2, for Secretor candidate 1 and 2. Sec1 and Sec2 are separated by 12 kb and are 65.5 kb and 35 kb apart, respectively, from the FUT1 gene. We used a cosmid-dependent direct cDNA selection method to clone a cDNA corresponding to a transcript that emanates from Sec2. This cDNA detects a 3.35-kb transcript in human tissues known to express the Se locus. Together with sequence and expression data reported in the accompanying article (Kelly, R. J., Rouquier, S., Giorgi, D., Lennon, G. G., and Lowe, J. B. (1995) J. Biol. Chem. 270, 4640-4649), these data demonstrate that Sec2 corresponds to the human Se blood group locus (FUT2). Our results furthermore define the physical relationship between the H and Se loci and confirm a hypothesis that these two loci represent distinct but closely linked alpha(1,2)fucosyltransferase genes.

Structure and Expression of the Gene Encoding Secretor‐Type Galactoside 2‐α‐l‐fucosyltransferase (FUT2)

“…Rouquier et al [13] have indicated that a 3.35-kb FUT2 transcript was detected in poly(A)-rich RNA from normal small intestine, colon and lung tissues. Transcripts of FUT2 with a similar size were detected by northern blot analysis of total RNA from ovarian cancer MCAS cells and colonic cancer WiDr cells but not from erythroleukemic HEL cells (Fig.…”

“…FUTI, FUT2, and a FUT2 pseudogene (Secl) have been isolated [ll-131. The putative amino acid sequences of these genes share a high degree of similarity and these genes are located within a 100-kb region on chromosome 19q13.3 [13], suggesting they were generated by gene duplication from the same ancestor gene and subsequently diverged. However, the cDNA of FUT2 has not been examined.…”

Divergent evolution and purifying selection of the H (FUT1) gene in New World monkeys (Primates, Platyrrhini)

“…The H enzyme is responsible for the expression of the H antigen in tissues derived from mesoderm and ectoderm, such as erythrocytes and vascular endothelial cells, and the Se enzyme for the expression of the same antigen in tissues derived from endoderm, such as epithelial cells of the digestive tract and exocrine glands (Watkins, 1980;Oriol et al, 1981Oriol et al, , 1986. The H and Se genes, and the Sec1 pseudogene constitute a cluster on the long arm of human chromosome 19 (19q13.3), where H is telomeric (Ball et al, 1991;Rouquier et al, 1994Rouquier et al, , 1995ReguigneArnould et al, 1995ReguigneArnould et al, , 1996.…”

Polymorphism of the human ABO‐Secretor locus (FUT2) in four populations in Asia: indication of distinct Asian subpopulations

“…The human ABO-Secretor locus (FUT2) is responsible for the production of ABO histoblood group substances in the gastrointestinal tract and secretions. Following the cloning of the FUT2 gene Rouquier et al 1995), analyses of FUT2 polymorphism have indicated the heterogeneity of FUT2 alleles and the ethnic specificity of both functional (Se) and non functional (se) alleles in various populations Koda et al 1996 ;Liu et al 1998Liu et al , 1999. The se%#) allele, which contains a nonsense mutation G428A and a further six base substitutions compared to the reference allele reported by Kelly et al (1995) (see Fig.…”