Does Dentistry Look Brighter With Genomics At Play?

Does Dentistry Look Brighter With Genomics At Play?

Here is an interesting story for you to read…..!

Back in the 1920s, Dr Louise O. Kappes (MD), Fellow in Pediatrics at the Mayo Clinic, Rochester, Minnesota, USA, observed increased numbers of new dental caries cases during the annual dental check up of school children at Rochester public schools. His curiosity enhanced as he found this caries incidence higher than all the cumulative observations made elsewhere in the northern states.

Dr Louise started his hunt to find the reason behind this new observation. He chose two groups of children for his study (as reported in Am J Dis Child. 1928;36(2):268-276):

  • “twenty-five with perfect or nearly perfect teeth”
  • “twenty-five with marked dental caries”

On 14th of March, 1928 his work “ Factors In The Decay Of Teeth” was received for publication. Dr Kappes’s work was one of the first attempts to find a hereditary component of a dental disorder i.e., dental caries.

Scientists then never stopped to explore genetic insights for dental and head and neck conditions!

From the pages of history till date, here goes a brief of the Milestones achieved during this long journey:

  • 1950s: An overview of dental diseases that were hereditary in nature was suggested (e.g, dentinogenesis imperfecta, dentin dysplasia, enamel hypoplasia, tooth agenesis, Ehlers-Danlos, ankyloglossia, and dental caries)
  • 1960s: Demonstration of genetic basis of missing last molar tooth (3rd molar agenesis)
  • 1970s: Hereditary component for gum related diseases suggested (Periodontal disease)
  • 1980s: Reports obtained from genetic analyses of cleft lip and cleft palate conditions (Orofacial Clefts)
  • 1990 -2000: Identification of specific genes namely AMELX, CFTR, PAX9, related to various dental defects of enamel, dentin and tooth development itself!
  • 2000 – 2010: First Genome wide association studies (GWAS) for periodontal disease and dental caries reported
  • 2020: Gene therapy for Ectodermal dysplasia (a group of conditions in which there is abnormal development of the skin, hair, nails, teeth, or sweat glands)
  • 2022: 114 genetic variants associated with oral cancer identified!

Picture Credit: Broad Institute

How Was This Possible?

All credit goes to the advent of the specialised field called Genomics.

The term genomics made a bold debut in an editorial by Victor McKusick and Frank Ruddle (1987), published in the first issue of the journal Genomics.

One of the most ambitious undertakings ever was launched: the Human Genome Project—a $2.7 billion, 15 year project carried out by an unprecedented collaboration of several US-based and international public and private institutions. The first draft of the human genome  was announced in 2001, and a finished sequence was achieved in 2003.

Picture Credit: Microbe Notes

The completion of the Human Genome Project gave birth to several other large projects that were extended or build on it:

  • The HapMap (International HapMap Consortium 2003)
  • ENCODE (ENCODE Project Consortium 2012)
  • 1000 Genomes Project Consortium (2015)
  • The Haplotype Reference Consortium 
  • The Human Microbiome Project

Through these endeavours several investigations have been undertaken during the last decades and several genomic markers (i.e., single markers, often referred to as single-nucleotide polymorphisms) associated with rare and common diseases or traits are now identified.

Picture Credit: Bitesize bio

At present, technological advances have made it possible to look through an entire human genome (i.e., whole genome sequencing) in a matter of days and at a cost of ~$1,000 or perhaps lesser!

What Information Do We Have In Hand At Present?

In this genomics era, technologies such as genome-wide association (GWAS) have helped to identify numerous genetic variations in the human genome for several oral and craniofacial diseases and traits, including:

  • periodontal disease
  • adult and childhood dental caries
  • tooth agenesis
  • orofacial clefts
  • cancers of the head and neck
  • orofacial pain and temporomandibular disorders
  • facial shape…..and more

Picture Credit: ZME Science

It also encouraged scientists to go a step ahead and look into the study of oral systemic disease connections by exploring genetic correlations between oral and systemic traits.

The Brighter Future of Dental Medicine With Genomics In Play

With the advent of more precision technologies, the available information will continue to increase, likely at an accelerated pace. The brighter future lies in translation of these genomics knowledge to molecular therapies to benefit the prevention of dental anomalies.With saliva being an accessible, easy-to-collect medium enabling genomic studies and with routine dental visits occurring at regular intervals, oral health professionals are in an advantageous position.

The realization that the human microbiome is key player for health, dentists now have a wider scope to understand the value of potentially sampling or monitoring the oral microbiome through meta- (i.e., microbial) genomics.

Direct-to-consumer genetic and genomics testing services are already a reality now. The latest frontier surpassed in the era of genomic medicine are gene therapies and gene editing with clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated nucleases (CRISPR/Cas) systems.

Picture Credit: Scientist.com

Precision cancer treatment, targeted pharmacotherapies, and prenatal testing and interventions are currently some of the most active areas for genomics applications. The opportunity for the oral and craniofacial domain is enormous and extends beyond the acceleration of mechanistic, biological research.

Potential applications include the development of precise molecular therapies, tissue engineering and craniofacial defect restoration, and microbiome- and pharmacotherapy-related interventions.

Picture Credit: doi: 10.1177/0022034519845674

What More Needs To Be Done?

An exciting opportunity is lying ahead for the oral health community and dentistry to accelerate their pace on both the discovery and education fronts. We need to work on:

  1. Improving the genomics literacy of current and future oral health professionals should be a priority.
  2. Encourage community engagement to increase the diversity and representativeness of genomics results
  3. Illuminating gaps and opportunities in translational program
  4. Sharing of genomics knowledge and the increase in genomics research diversity
“Genomic information can and will we used to keep people healthier and improve their lives -and with it , there remain the responsibilities to do no harm and reduce health inequalities ” – K. Divaris

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