A NOVEL 25 BP TANDEM REPEAT WITHIN THE HUMAN TREFOIL PEPTIDE GENE TFF2 IN 21Q22.3 - POLYMORPHISM AND MAMMALIAN EVOLUTION

Trefoil peptides belong to a family of small secretory proteins charac terised by three intrachain disulfide bonds forming the trefoil motif (TFF-domain), They serve to maintain or repair the epithelial mucosa, and promote cell migration, They are predominantly found in gastrointe stinal tissues, and are upregulated around areas of epithelial damage, and in meta-and neoplasia. The corresponding three genes are clustere d in human 21q22.3. TFF2 is the only human one encoding two TFF-domain s on separate exons, In between (intron 2), a novel 25 bp sequence is located that is tandemly repeated approximately 48 times, but is uniqu e in the human genome. A diallelic polymorphism with a second allele c omprising approximately 53 repeat units is present among individuals. Both alleles were cloned on BAC recombinants, In Caucasians (n = 78) t he allele frequencies found are 0.85 and 0.15, respectively, represent ing a frequency of heterozygosity of 26%. Ape and monkey species exhib it homologous repeats of shorter total array length, whereas none is f ound in other mammals.