Amelogenin

Amelogenin is a protein found in developing tooth enamel, and it belongs to a family of extracellular matrix (ECM) proteins. Developing enamel contains about 30% protein, and 90% of this is amelogenins. Other significant proteins in enamel are ameloblastins, enamelins, and tuftelins.

Function
Although not completely understood, the function of amelogenins is believed to be in organizing enamel rods during tooth development. The latest research indicates that this protein regulates the initiation and growth of hydroxyapatite crystals during the mineralization of enamel. In addition, amelogenins appear to aid in the development of cementum by directing cells that form cementum to the root surface of teeth.

Variants
The amelogenin gene is a single copy gene, homologues of which are located on Xp22.1-Xp22.3 and Yp 11.2 [5].

Application in sex determination
The gene for amelogenin can be used in sex determination of samples from unknown human origin through the Polymerase Chain Reaction (PCR). Using primers specific for intron 1 of the gene, the gene sequence for the intron can be amplified. The X chromosome gene, AMELX, gives rise to a 106 bp amplification product (amplicon) and the Y chromosome gene, AMELY, a 112 bp amplicon. Hence, the AMELX contains a 6 bp deletion in the intron 1. Therefore, when the amplicons are run on an agarose gel, samples from male sources (XY) will show two bands on an agarose gel (one for the 106 bp fragment and one for the 112 bp fragment), whereas females (XX) will show only one band. Thus, this process allows for sex determination of unknown samples.

However, mutations in the Y-derived fragment of the gene may result in amplification failure of the Y allele, causing misidentification of the biological sample as of a female. The error rate is not much. In one study, amelogenin test was undertaken on 1224 individuals participating in a biomedical study and the concordance between referred sex in the database and amelogenin test was estimated. It was found that the overall concordance rate was 99.84% (1222/1224). Only two individuals were reported as having a different sex using amelogenin (than their actual sex).

Indians however seem to have an unusually high rate of amelogenin deletion in Y-chromosomes. In one study, Thangaraj and colleagues studied a total of 270 male samples, of which 5 males showed a deletion of Y chromosome specific amelogenin (1.85%). The authors proposed to call them “deleted-amelogenin males” (DAMs), who but for the detection of the presence of other Y-specific markers (e.g. SRY, STR and 50f2) would have been identified as females. Considering the consequences of the result obtained only using the amelogenin marker, the authors suggested the use of additional Y chromosome markers for unambiguous gender identification.

Clinical significance
Mutations in AMELX can cause amelogenesis imperfecta, a disorder of tooth enamel development.