Amelogenin
Encyclopedia
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 ameloblastin
s, enamelin
s, and tuftelin
s.
s 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.
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.
, a disorder of tooth enamel development.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
found in developing tooth
Tooth
Teeth are small, calcified, whitish structures found in the jaws of many vertebrates that are used to break down food. Some animals, particularly carnivores, also use teeth for hunting or for defensive purposes. The roots of teeth are embedded in the Mandible bone or the Maxillary bone and are...
enamel
Tooth enamel
Tooth enamel, along with dentin, cementum, and dental pulp is one of the four major tissues that make up the tooth in vertebrates. It is the hardest and most highly mineralized substance in the human body. Tooth enamel is also found in the dermal denticles of sharks...
, and it belongs to a family of extracellular matrix (ECM)
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
proteins. Developing enamel contains about 30% protein, and 90% of this is amelogenins. Other significant proteins in enamel are ameloblastin
Ameloblastin
Ameloblastin, also known as amelin, is a gene-specific protein found in tooth enamel. Although less than 5% of enamel consists of protein, ameloblastins comprise 5%-10% of all enamel protein. This protein is formed by ameloblasts during the early secretory to late maturation stages of amelogenesis...
s, enamelin
Enamelin
Enamelin was described in older literature as an EDTA soluble enamel protein. It accounts for the organic portion of enamel, which represents 4% of enamel's mass. It turned out in recent research to be albumin derived from blood contamination....
s, and tuftelin
Tuftelin
Tuftelin is an acidic phosphorylated glycoprotein found in tooth enamel. In humans, the Tuftelin protein is encoded by the TUFT1 gene.- Function :This protein is formed for a short time during amelogenesis...
s.
Function
Although not completely understood, the function of amelogenins is believed to be in organizing enamel rodEnamel rod
An Enamel rod is the basic unit of tooth enamel. Measuring 4 μm wide to 8 μm high, an enamel rod is a tightly packed, highly organized mass of hydroxyapatite crystals...
s during tooth development
Tooth development
Tooth development or odontogenesis is the complex process by which teeth form from embryonic cells, grow, and erupt into the mouth. Although many diverse species have teeth, non-human tooth development is largely the same as in humans...
. 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
Cementum
Cementum is a specialized calcified substance covering the root of a tooth. Cementum is excreted by cells called cementoblasts within the root of the tooth and is thickest at the root apex. These cementoblasts develop from undifferentiated mesenchymal cells in the connective tissue of the dental...
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 primersPrimer (molecular biology)
A primer is a strand of nucleic acid that serves as a starting point for DNA synthesis. They are required for DNA replication because the enzymes that catalyze this process, DNA polymerases, can only add new nucleotides to an existing strand of DNA...
specific for intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
1 of the gene, the gene sequence for the intron can be amplified. The X chromosome
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
gene, AMELX
AMELX
Amelogenin, X isoform is a protein that in humans is encoded by the AMELX gene.Amelogenin, X isoform is a form of amelogenin found on the X chromosome. Amelogenin X is a member of the amelogenin family of extracellular matrix proteins...
, gives rise to a 106 bp amplification product (amplicon) and the Y chromosome
Y chromosome
The Y chromosome is one of the two sex-determining chromosomes in most mammals, including humans. In mammals, it contains the gene SRY, which triggers testis development if present. The human Y chromosome is composed of about 60 million base pairs...
gene, AMELY
AMELY
Amelogenin, Y isoform is a protein that in humans is encoded by the AMELY gene.AMELY is a gene which encodes a form of amelogenin found on the Y chromosome. Amelogenin is a member of a family of extracellular matrix proteins. They are involved in biomineralization during tooth enamel development...
, 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 imperfectaAmelogenesis imperfecta
Amelogenesis imperfecta presents with abnormal formation of the enamel or external layer of teeth. Enamel is composed mostly of mineral, that is formed and regulated by the proteins in it...
, a disorder of tooth enamel development.