title: A study of polymorphism in human AMELX.
abstract: Amelogenin gene (AMEL) encodes for a protein that plays important roles in the organization and structure of enamel. A recent evolutionary analysis of AMELX in mammals has revealed, aside to well-conserved 5' and 3' regions, a variable region located in the largest exon (exon 6), which strongly suggested the possible existence of polymorphism in human AMELX. A detailed analysis of this region was of fundamental importance for genetic studies. We have looked for variations in human AMELX exon 6 from 100 AMELX alleles in a randomized European population, using denaturing high-performance liquid chromatography (dHPLC). We also have looked for AMELX variants in databases, and compared this region in nine primates. There were no variations in the AMELX sequences analysed, but two synonymous single-nucleotide polymorphisms were found in databases. Alignment of the primate exon 6 sequences revealed that AMELX is highly constrained, as illustrated by 100% nucleotide identity found between humans and chimpanzee, and from 99.9 to 94.8% nucleotide identity in the other species. In contrast to what was suspected from the evolutionary analysis, we conclude that AMELX polymorphism should occur at low level in humans. This finding leads us to speculate that the high constraint observed in primate AMELX is related to its location on the X chromosome, and is due to selection at a single locus.
authors.affiliation: UFR d'Odontologie, 16 cours de la Marne, 33082 Bordeaux, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Richard
authors.forename: Sidney
authors.initials: S
authors.lastname: Delgado
authors.forename: Philippe
authors.initials: P
authors.lastname: Gorry
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Sire
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics; D053523:Amelogenin / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D030541:Databases, Genetic; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011323:Primates / Q000235:genetics*; D016415:Sequence Alignment; D014960:X Chromosome
chemical_list: D053523:Amelogenin