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 Table of Contents  
Year : 2014  |  Volume : 26  |  Issue : 1  |  Page : 62-68

Human genetics in oral medicine: A review

1 Department of Oral Medicine and Radiology, Rishiraj College of Dental Sciences and Research Centre, Bhopal, Madhya Pradesh, India
2 Department of Dental Surgery, Ranchi Institute of Neuro-Psychiatry and Allied Sciences, Ranchi, Jharkhand, India
3 Department of Oral Medicine and Radiology, Rama Dental College Hospital and Research Centre, Kanpur, Uttar Pradesh, India
4 Department of Oral and Maxillofacial Surgery, Mahatma Gandhi Dental College, Jaipur, Rajasthan, India

Date of Submission27-May-2014
Date of Acceptance11-Sep-2014
Date of Web Publication26-Sep-2014

Correspondence Address:
Manas Gupta
Department of Oral Medicine and Radiology, Rishiraj College of Dental Sciences and Research Centre, Bhopal, Madhya Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-1363.141860

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In this modern era, oral health practice has become evidence-based dentistry. Genes are hereditary blueprints of human beings. Studies at the molecular levels have revolutionized maxillofacial disorders, and genomic information has done wonders to the cause. This article reviews the previous and current application of human genetics in craniofacial development and disorders, which may lead to individualized treatment and prevention plans in the future.

Keywords: Evidence-based dentistry, human genome, molecular dentistry

How to cite this article:
Gupta M, Jyoti B, Srivastava R, Pachauri A. Human genetics in oral medicine: A review . J Indian Acad Oral Med Radiol 2014;26:62-8

How to cite this URL:
Gupta M, Jyoti B, Srivastava R, Pachauri A. Human genetics in oral medicine: A review . J Indian Acad Oral Med Radiol [serial online] 2014 [cited 2022 Oct 4];26:62-8. Available from: https://www.jiaomr.in/text.asp?2014/26/1/62/141860

   Introduction Top

Genetics is the study of genes at all levels, from molecules to populations. [1] In 1909, the British biologist William Bateson coined the science of inheritance as genetics, and in the early 1950s, James Watson and Francis Crick discovered the molecular structure of deoxyribonucleic acid (DNA). Genetics got excellent encouragement after the completion of the Human Genome Project in October 2004, which revealed that a human being contains 20,000 to 25,000 genes within the nucleus of each somatic cell and another nine genes that are encoded within the mitochondria found in all human cells. Genes contain information for proteins and represent hereditary blueprints. [2] In dentistry we encounter numerous differences in the dentofacial characteristics of individuals. [1]

Genetic disorders are caused by abnormalities in the genetic sequences and chromosome structure, which are induced by single-base substitutions or missense mutations. Genetic information is stored in codon sequences on the DNA, which are propagated from a parent to the progeny cells, through DNA replication. Simultaneously the information is transformed into mRNA and successively into an amino acid sequence of a protein according to the genetic code. [1] Karyotyping enables visualization of the number and fidelity of human chromosomes. There are 46 chromosomes found in every nucleus of every diploid somatic cell in the human body. These chromosomes contain double-stranded DNA and associated proteins, approximately 6 feet in length. Of the 46 chromosomes that contain DNA, 44 are termed 'autosomes' that exist in homologous pairs and the remaining two chromosomes are termed 'sex chromosomes'. [2]

   Basic Principles of Genetics Top

Nageli, the Swiss botanist, in the 1840s, named the thread-like structures in the nuclei of plant cells as 'transitory cytoblasts'. Later, this term, was renamed by Waldeyer as 'chromosome' ('chroma' meaning color and soma meaning body in Greek), in 1888.


Cytogenetics is the study of the structure and properties of chromosomes, chromosomal behavior during somatic cell division in growth and development (mitosis), germ cell division in reproduction (meiosis), chromosomal influence on the phenotype, and the factors that cause chromosomal changes. [3] In this modern era, various genome-wide detection methods are used to identify genetic alterations, such as, chromosomal aberrations and rearrangements, loss of heterozygosity (LOH) or allelic imbalance, and segmental copy number variation. [4]


It is defined as any change in the sequence of nucleic acids within the DNA that can be silent without clinical symptoms or can be aggressive in a variety of ways, such as, gain or loss of function mutations. It is of two types: [2]

  1. Single-gene/point mutation: It affects only one nucleotide with the substitution of one for another.
    1. Missense mutation - It is due to a change of a codon by translation, which alters the primary structure of the protein product, for example, sickle-cell anemia, craniosynostosis, osteogenesis imperfecta and amelogenesis imperfecta.
    2. Silent mutation - It has no effect on the transcription or translation process.
  2. Chromosomal/macromolecular mutations: It affects large numbers of genes encoded in the specific regions of DNA detected microscopically by karyotypic analysis, which includes deletions, duplications, inversions, and translocations from one chromosome to another.

Mutational and gene expression analysis of known tumor suppressors and oncogenes helps in the detection of early tumor initiation as well as cancer progression. [4] Segregation analysis is a statistical method for determining the mode of inheritance of a particular phenotype from the family data, particularly with the aim of elucidating single gene effects or the so-called major genes. Positional cloning/reverse genetics is used to identify the location of the mutant gene on a particular chromosome, by virtue of its co-segregation with polymorphic DNA markers. [5]

   Nutritional Genomics/Nutrigenomics Top

The working definition of nutrigenomics states that it is 'something that seeks to provide a genetic and molecular understanding of how common dietary chemicals (i.e., nutrients) affect the balance between health and disease by altering the expression and/or structure of an individual's genetic makeup'. [6] Dietary chemicals include nutrients and bioactive chemicals that do not directly produce energy, but exclude man-made chemicals such as pesticides.

This new branch of genomic and nutritional research can best be summarized with the following five tenets: [6]

  • Common dietary chemicals act on the human genome, directly or indirectly, to alter gene expression or structure.
  • Under certain circumstances and in some individuals, diet can be a serious risk factor for a number of diseases.
  • Some diet-regulated genes (and their normal, common variants) are susceptibility genes and likely to play a role in the onset, incidence, progression, and/or severity of chronic diseases.
  • The degree to which diet influences the balance between healthy and disease states may depend on an individual's genetic makeup.

Dietary intervention based on the knowledge of nutritional requirement, nutrition status, and genotype (i.e., individualized nutrition) can be used to prevent, mitigate or cure chronic disease. [6]

   Pharmacogenomics/Pharmacogenetics Top

It provides new insights into how human genetic variations influence individual drug absorption and utilization during therapy, determined by intrinsic genetic factors. Biomimetics refers to human-made processes, substances, devices or systems that imitate nature. It is applied to molecular dentistry to improve soft and hard tissue engineering, as well as tooth and salivary gland organ regeneration. The science and technology of miniaturization/nanotechnology enables rapid and sensitive analysis by using saliva as a diagnostic fluid. [7] Recent advances in cell isolation techniques and miniaturization of genomic technologies have enabled comprehensive molecular profiling of selected cell types and high resolution mapping of gene disruption associated with specific disease phenotypes. [4]

   Environmental-Gene Correlation Top

After completion of the Human Genome Project, epidemiologists can now study thousands of genes and their interaction with the environment. Botto et al. emphasized on the gene-environment interaction and proposed the two-by-four table as the fundamental unit of epidemiological analysis. [7] Hinh et al. highlighted the connection between environmental and genetic factors leading to human diseases, with a telomere dysfunction in their study. [8]

   Regulation and Function of Genes Top

Genes function through a complex series of processes and control by mRNA production, known as, transcriptional control. Genes encode the highly conserved consumption factors such as HOX-genes, PAX-genes, and T-Box genes. During transcription, the genes are encoded within the DNA templates, which are copied into the mRNAs, which in turn, leave the nucleus and migrate into the cytoplasm. Mutations in one or more transcription factors (e.g., MSX1, MSX2, DLX5, and PAX9) may arrest or retard tooth development. In translation, mRNA is translated into a precise sequence of amino acids known as polypeptide or protein. Mutations in type-I collagen and/or DSPP exhibit as dentinogenesis imperfecta. Regulation of genes includes various sequences, which are as follows: [2]

  1. Combinations of multiple transcription factors bind to one another (i.e., protein - protein binding).
  2. Methylation of cytosine within nucleic acid sequences.
  3. An enzyme, RNA polymerase II, attaches to a specific sequence within the DNA and is then followed by the transcription process (DNA to mRNA), followed eventually by translation (mRNA to protein amino acid sequence) on ribosomes, physically located within the cytoplasm of cells.

Various Specialized Cytogenetic methods for chromosome analysis: [3]

  1. Whole blood - culture: It is one of the most easily accessible with good growth potential after mitogenic stimulation.
  2. Short-term culture: It is used for preparation of chromosomes by the peripheral blood culture.
  3. Bone marrow- culture: It is used to identify chromosome anomalies in hematopoietic cells.
  4. Banding techniques: It allows precise identification of each chromosome and detects the structural chromosomal rearrangements.
    1. Q-banding requires a fluorescent microscope for analysis.
    2. G-banding is done by treating the chromosomes with trypsin that alters the structure of the proteins, followed by staining with a Giemsa solution, which leads to permanent preparations and is used to pair and identify each of the human chromosomes accurately.
    3. R-banding involves thermal denaturation in Earle's balanced salt solution (at 87°C), but the staining ability of the chromosomes is lost due to heating.
    4. C-banding localizes the heterochromatic regions of the chromosomes with multiple centromeres. It helps in distinguishing between the donor and recipient cells during bone marrow transplantation.
    5. T-banding involves staining the telomeric end regions of the chromosomes.
    6. The CT-banding method is used to stain both the centromeric heterochromatin as well as the telomere of chromosomes.
    7. The choice of a banding technique for routine analysis and the banding technique using trypsin and Giemsa became the most accepted worldwide.
    8. Nucleolar organizing region (NOR) banding: It stains the NORs of chromosomes, which are located in the satellite stalks of acrocentric chromosomes and house genes for ribosomal RNA.
    9. Sex chromatin analysis: The number of sex chromatin bodies is one less than the number of X chromosomes in the chromosome complement. The presence of a chromatin mass known as the Barr body indicates a chromatin-positive cell.
  5. Sister chromatid exchange (SCE) staining: It is accomplished in cell cultures by incorporating bromodeoxyuridine (BrdU), in place of thymidine, into the replicating cells for two cell cycles.
  6. Fluorescent in situ hybridization (FISH): In 1986, Pinkel et al. developed a method to visualize chromosomes using fluorescent-labeled probes. This method allowed visualization of chromosomal and nuclear locations of specific DNA sequences under the microscope, either in metaphase or interphase cells. It detected chromosomal abnormalities in small segments of DNA, helped karyotypic analysis of non-dividing cell nuclei, and was involved in denaturing genomic DNA.
  7. Spectral karyotyping (SKY) and multicolor FISH (M-FISH): It allows all the 24 human chromosomes to be painted in different colors and allows detecting of translocations and other complex chromosomal aberrations.
  8. Comparative genomic hybridization (CGH): It detects the changes and variation within the human genome. Amniocentesis is an invasive, well-established, safe, reliable, and accurate procedure done during pregnancy to detect chromosomal abnormalities or specific genetic diseases.

   Principles of Dental Genetic Variation Top

Tyagi et al. summarized the dental genetic variation principles in their literature: [1]

  1. The Butler's field theory suggested that the key tooth has the highest heritability and multiple genes are responsible for the tooth eruption heritability.
  2. Polygenic inheritance is due to congenital missing teeth.
  3. Odontogenesis is initiated by the transmission of genetic change in the RNA.
  4. Both genetic and environmental factors fixed interaction has a continuous altering nature, which determines the dentofacial morphology.
  5. Susceptibility of caries is mainly due to host genes.
  6. The genetic component is present in early onset forms of periodontal disease like juvenile periodontitis and rapidly progressing periodontitis.

   Genetic Diseases and Disorders Top

They are broadly classified as: [2]

  1. Single gene or Mendelian disorders - rare and familial, for example, hemophilia.
  2. Chromosomal anomalies - sporadic, for example, Down syndrome.
  3. Multifactorial disorders or complex human diseases - multiple genes are involved with environmental factors, for example, congenital craniofacial malformations and temporomandibular disorders.
  4. Acquired somatic genetic disease, for example, cancers.

Mendelian diseases and disorders are inherited human diseases caused by a mutation in a single gene, which can be transmitted within families, in a dominant or recessive mode. A dominant disease occurs when one of the two copies of a given gene bears a deleterious mutation, which can be traced through family pedigrees and appears to spread vertically, because everyone carrying a dominant mutant allele shows the disease symptoms. A disease displays a recessive inheritance pattern when two abnormal copies of the gene are present in the affected individual, common in consanguineous marriages. In an X-linked dominant disease, both males and females are affected, but the females are usually less severely affected. X-linked dominant inheritance can manifest in either sex, with more affected females than males. All female children of an affected male are affected and all children of an affected female have a 50% chance of being affected. In X-linked recessive inheritance, only males are affected. Females are typically carriers with no symptoms or very mild symptoms. [2] Various authors have put forward the role of genetic mutations in craniofacial, as well as dental hard and soft tissue defects, in literature [Table 1]. [9],[10],[11]
Table 1: Syndromes associated with craniofacial defects due to genetic mutation

Click here to view

The X and Y chromosomes effect the tooth crown size as well as craniofacial growth and development. The X-chromosome mainly regulates enamel thickness, whereas, the Y chromosome affects both enamel and dentin. [5]

Chromosomal diseases and disorders are due to incorrect chromosomal number, large chromosomal structural defects, and uniparental disomy. Mitochondrial diseases and disorders are inherited from the mother, through maternal mitochondria, which are transmitted while forming the zygote in early embryogenesis. The complex human diseases and disorders are craniofacial malformations, tooth decay, periodontal disease, and birth defects caused by multiple genes with environmental factors, and appear to cluster in families over multiple generations. [2]

Various studies reveal that genes play an essential role in dental caries pathogenesis, and certain allelic genes of enamel protein, salivary proline-rich proteins, taste, and human leukocyte antigen (HLA) complex, cause a variation in caries susceptibility. Knowledge of a genetic predisposition and/or a family correlation to the host bacteria associated with dental caries helps the patient and their families in prophylactic treatment. [12]

Cancer is a genetic disease initiated by alterations in oncogenes and tumor suppressors that regulate cell proliferation, survival, and other homeostatic functions. Gain/loss of gene function is predominantly responsible for oncogenic transformation. [13] Kolokythas et al. have concluded in their study that several microRNAs deregulated in oral cancer and their exact target genes have been identified, which helps in targeted therapy, with improved outcome results. [14] The process of 'oncogene activation' plays a major role in the development of oral cancer caused by viruses. In this process, viruses can get into the cells of the oral cavity and change the genes in them to form a cancer cell. The viruses responsible for oral cancer are Human Papilloma Virus (HPV), particularly the HPV-16 and the HPV-18 strains. Herpes Viruses are now considered contributors to some oral cancers. The genes encoded within these viruses are involved in the initiation of the multiple steps needed for a normal cell to become malignant. Two genes, Rb and p53 regulate normal cell division. Rb has the role of separating the transcription factors needed for progression through the cell cycle, preventing the normal cells from dividing until they have separated enough transcription factors. Rb is a tumor suppressor gene that segregates a protein called E2F. When normal cells are infected with HPV, the E7 gene from the HPV binds to Rb, releasing E2F and other proteins, signaling the start of the cell cycle. This cycle continues as long as E7 remains attached to Rb. Uncontrolled cell division is a sign of malignancy. The other gene that HPV attacks is the p53 gene, responsible for the repair of damaged DNA and apoptosis, in the event that repair is impossible. In malignant cells, p53 is often nonfunctional or missing entirely. The viral E6 protein binds to p53 making it nonfunctional. The damaged DNA is then replicated continually, as the nonfunctional or missing p53 does not initiate apoptosis. The E6 protein also activates telomerase, an enzyme that synthesizes the telomere repeat sequences. The activation of this enzyme ensures a repeated cell cycle that continually produces more viral cells, leading to malignancy. [15]

Hypodontia/Oligodontia is a condition in which dental agenesis occurs. In hypodontia, one to six teeth (excluding the third molar) are missing and in oligodontia more than six teeth (excluding the third molar) are missing. Only four genes have been identified to be associated with non-syndromic hypodontia/oligodontia, which represents less than 5% of the total cases. The identified genes are:

  • MSX1 - hypodontia NS
  • PAX9 - oligodontia NS
  • AXIN2 - oligodontia associated with colorectal cancer
  • EDA1 - oligodontia NS

Located on the short arm of chromosome 4 (4p16.1-p16.3), the MSX1 gene has a homeobox sequence and two exons that encode a homeodomain - a 297 amino acid protein. The gene plays an important role in craniofacial development, including odontogenesis. Thus far, three mutations in exon 1 and four in exon 2 have been associated with hypodontia affecting PM2 and M3 predominantly or cleft-associated hypodontia. MSX1 phenotypes caused by the protein deficiency depend on the location of the mutations and their effect on the structure and function of the protein. Stockton et al. showed that otherwise normal individuals with missing permanent molars caused by the mutation in the PAX9 gene (G219 insertion in exon 2) modified the open-reading frame (frameshift mutation) causing premature termination of the translation.

X-linked hypohidrotic ectodermal dysplasia (HED) is caused due to mutation in the EDA1 gene (Xq12-q13.1). It is a rare disease characterized by hypoplasia or absence of sweat glands, dry skin, sparse hair, and pronounced oligodontia. In 2009, Song et al., identified three new mutations of the EDA gene (Ala259Glu, Arg289Cys, and Arg334His) in four male individuals (27%), from 15 analyzed individuals with non-syndromic oligodontia. Kantaputra and Sripathomsawatin in 2011, reported that non-syndromic hypodontia can be caused by mutations in the WNT10A gene (apart from few more reported genes such as MSX1, PAX9, AXIN2, and EDA1). [16]

Amelogenesis imperfecta (AI) is a developmental condition with a genetic mutation, which affects the structure and clinical appearance of enamel. It may show autosomal dominant, autosomal recessive, sex-linked, and sporadic inheritance patterns. [17] By using the genetic molecular technique, the amelogenin gene is found to be present on the distal portion of the short arm of the X chromosome and in the peri-centromeric region of the Y chromosome. [5] Mutations in the three structural genes that cause AI are as follows: [2]

  1. The AMELX gene (amelogenin), the most prevalent in forming the enamel extracellular matrix with genes located on both the X and Y chromosomes.
  2. The ENAM gene (enamelin), located on chromosome 4 and the second most prevalent protein in forming the enamel matrix.
  3. MMP 20 gene (metalloprotease enzyme) causes time- and position-specific protein degradation related to calcium hydroxyapatite crystal formations.

   Future of Human Genetics and Oral Physicians Top

Genetics is the emerging branch in dental and medical education of the twenty-first century. Oral physicians are instrumental in closing the gap between medicine and dentistry, which helps in the detection, prevention, and management of conditions that affect systemic and oral health. Diagnosis will encompass the cardinal features of the clinical phenotype, differential diagnosis, and sensitive and specific tests for one or more genes and/or gene products. All dentists and physicians should consider the genetic variability with the environmental interactions affecting the patient. Genetic counseling will encompass legal and psychosocial management issues related to genetic screening, privacy and confidentiality, disclosure of unexpected and unwanted findings, and obligations to identify and communicate difficult issues. Interaction between human genetics and microbial genomics, proteomics, metabolomics, and pharmacogenomics will brighten the future of the dental and medical health profession. [2]

   Conclusion Top

The extra feather of genetics to oral diseases will enhance the understanding of disease etiology and allow for an earlier diagnosis, with preventative measures, prior to disease onset, with the help of advanced genomic molecular technologies. It is vital that the dentist, patients, and policymakers be aware of these genomic approaches. Genetics, its understanding, and applications, enhance our ability to understand the growth and development of craniofacial structures, leading to the early intervention and prevention of disease onset. Dental health caregivers should be aware of the technological and scientific advancements in the field of genetic testing and at the same time have ethical restraints over unrealistic expectations from it.

   References Top

1.Tyagi R, Khuller N, Sharma A,Khatri A. Genetic basis of dental disorders: A review. J Oral Health Comm Dent 2008;2:55-61.  Back to cited text no. 1
2.Burket LM. Basic principles of human genetics: A primer for oral medicine. In: Greenberg MS, Glick M, Ship JA, editors. Burket's Oral Medicine. 11 th ed. Ontario, Canada: BC Decker Inc; 2008. p. 549-68.  Back to cited text no. 2
3.Ponnuraj KT. Cytogenetic techniques in diagnosing genetic disorders. In: Ikehara K, editor. Advances in the Study of Genetic Disorders. Croatia InTech; 2011. p. 45-64.  Back to cited text no. 3
4.Garnis C, Buys TP, Lam WL. Genetic alteration and gene expression modulation during cancer progression. Mol Cancer 2004;3:9.  Back to cited text no. 4
5.Townsend GC, Aldred MJ, Bartold PM. Genetic aspects of dental disorders. Aust Dent J 1998;43:269-86.  Back to cited text no. 5
6.Kaput J, Rodriguez RL. Nutritional genomics: The next frontier in the postgenomic era. Physiol Genomics 2004;16:166-77.  Back to cited text no. 6
7.Botto LD, Khoury MJ. Commentary: Facing the challenge of gene-environment interaction: The two-by-four table and beyond. Am J Epidemiol 2001;153:1016-20.  Back to cited text no. 7
8.Ly H. Genetic and environmental factors influencing human diseases with telomere dysfunction. Int J Clin Exp Med 2009;2: 114-30.  Back to cited text no. 8
9.Kavitha B, Priyadharshini V, Sivapathasundharam B, Saraswathi TR. Role of genes in oro-dental diseases. Indian J Dent Res 2010;21:270-4.  Back to cited text no. 9
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10.Rajendran R, Sivapathasundaram B, editors. Shafer's Textbook of Oral Pathology. 5 th ed. New Delhi: Elsevier; 2006. p. 941-1038.  Back to cited text no. 10
11.Gorlin RJ, Pindborg JJ. Syndromes of the Head and Neck. 1 st ed. New York: McGraw-Hill Book Company; 1964. p. 261-5; 419-25.  Back to cited text no. 11
12.Renuka P, Pushpanjali K, Sangeetha R. Review on "Influence of host genes on dental caries". IOSR J Dent Med Sci 2013;4:86-92.  Back to cited text no. 12
13.Bhatt AN, Mathur R, Farooque A, Verma A, Dwarakanath BS. Cancer biomarkers- current perspectives. Indian J Med Res 2010;132:129-49.  Back to cited text no. 13
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14.Kolokythas A, Miloro M, Zhou X. Review of microRNA proposed target genes in oral cancer. Part II. J Oral Maxillofac Res 2011;2:e2.  Back to cited text no. 14
15.Kaweckyj N. Oral cancer genetics: From diagnosis to treatment. Crest® + Oral-B® at dentalcare.com Continuing Education Course, Revised July 16, 2014. Available from: http: // www.media.dentalcare.com/media/en-US/education/ce72/ce72.pdf. [Last accessed on 2014 Aug 10].  Back to cited text no. 15
16.Ghergie M, Cocîrla E, Lupan I, Kelemen BS, Popescu O. Genes and dental disorders. Clujul Medical 2013;86:196-9.  Back to cited text no. 16
17.Crawford PJ, Aldred M, Bloch-Zupan A. Amelogenesis Imperfecta. Orphanet J Rare Dis 2007;2:17.  Back to cited text no. 17


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