Tooth enamel is the most highly mineralized tissue in vertebrates. Enamel crystal formation and elongation should be well controlled to achieve an exceptional hardness and a compact microstructure. Enamel matrix calcification occurs with several matrix proteins, such as amelogenin, enamelin, and ameloblastin. Among them, amelogenin is the most abundant enamel matrix protein, and multiple isoforms resulting from extensive but wellconserved alternative splicing and postsecretional processing have been identified. In this report, we recruited a family with a unique enamel defect and identified a silent mutation in exon 4 of the AMELX gene. We show that the mutation caused the inclusion of exon 4, which is almost always skipped, in the mRNA transcript. We further show, by generating and characterizing a transgenic animal model, that the alteration of the ratio and quantity of the developmentally conserved alternative splicing repertoire of AMELX caused defects in enamel matrix mineralization.

Microsatellite markers are an essential tool for genetic linkage analysis because of their high polymorphism content. Four hundred commercially available markers covering the entire genome were genotyped from 578 sib individuals from 249 Korean families. Allelic frequencies and heterozygosities were determined for each marker loci and compared between Korean, Taiwanese, Japanese and Caucasian populations. In the three Asian populations, 10-13% of the markers had less than 0.6 heterozygosity, whereas in the Caucasian population, only 0.5% of the markers had less than 0.6 heterozygosity. Mean identical by descent (IBD) values were calculated for 578 sib individuals.Analysis of IBD values greater than 0.5 suggested that markers with low heterozygosity can also provide positive linkages, at least for the IBD sharing method of model-free linkage analysis. The data presented in this study will be a useful reference for genome-wide screens of Koreans and comparative studies with other ethnic populations.