PRESENTATION & DIAGNOSIS OF GENETIC DISORDERS & THEIR RELEVANCE TO OROFACIAL DEVELOPMENT & SUSCEPTIBILITY TO ORAL DISEASE

why does genetics matter in dentistry

• genetic influence on oral structures

• relevance to diagnosis and treatment

• precision dentistry is an emerging field i.e. personalised medicine

gene expression diagram

at what levels can gene expression be modified

• transcriptional control

• post-transcriptional regulation incl. post-translational regulation

• epigenetics

a lot of genes that control orofacial development are…

transcription factors

diagram of regulation of transcription in eukaryotic cells

diagram of post-translational regulation

(these are different types of RNA decay mechanisms)

what is ARE and its function

• ARE = adenine response elements

• ARE decide how long the RNA is going to hang around (lengthens/ shortens poly-A tail)

what is a big class of ncRNA

miRNA is one of the biggest classes of ncRNA

what do a, b and c do

• fine tuning how much of a gene is being expressed

what does d do 

• defence mechanism that recognises RNA that is wrong and destroys it e.g. from a bacteria or a virus

• machinery recognises short transcripts or strange sequences 

what processes are involved in histone modification

• methylation

• acetylation

» alters which part of DNA can be transcribed to RNA and which are not

histone modification is generally ___________

acetylation

diagram showing gene expression in tooth organogenesis

• red box = if these are removed, tooth dev. will arrest at this stage

• bold genes in yellow background = ‘doers’ or growth factors

• italics genes in yellow background = mostly transcription factors

what can growth factors genes be switched on by

transcription factors

give examples of transcription factors and what they control 

• Msx1, Shox2 and the Pbx family of transcription factors control the expression of other genes involved in palate formation

give examples of growth factors and their receptors and their function 

• BMP4, FGF10 and SHH play essential roles in cell to cell communication and are part of a feedback loop that regulates palatal development 

palatal development is ___ understood than tooth development

less

what are a lot of ageing effects in the oral cavity mostly due to 

• a lot of ageing effects in the oral cavity are mostly due to epigenetic changes 

• not mutations in DNA sequences

list common developmental anomalies

• hypodontia

• cleft lip and palata

• amelogenesis imperfecta

diagram of genes in hypodontia

what genes are associated to cleft palate development

• Msx1

• Osr2

outline amelogensis imperfecta 

• group of inherited conditions that affect the development of tooth enamel

• this results in teeth that can be unusually small, discoloured, pitted or prone to rapid wear and breakage

• often results in pain due to sensitivity resulting from lacking enamel

• differing severity depending on which genes are involved

table showing genes involved in amelogenesis imperfecta

which gene is associated with periodontal disease

• IL-1 gene variants implicated in periodontal disease

• increased inflammation

table showing classification of oral genetic disorders

define ectodermal dysplasia

ectodermal dysplasia: a group of genetic disorders that affect the development of hair, nails, teeth, skin and sweat glands

outline the effects of ectodermal dysplasia on the teeth

• missing teeth (hypodontia or anodontia)

• unusual tooth shape

• delayed eruption

• defective enamel

• reduced saliva (dry mouth)

• abnormal roots and pulp chambers

outline genes associated with ectodermal dysplasia

• results from mutations in one or more of several genes

• these include ectodysplasin A (EDA), its receptors EDAR and EDARADD and the transcription factor WNT10A

  • the EDA is often defective in ectodermal dysplasia

outline the oral implications of cystic fibrosis

• CF is linked to reduced saliva, medication side effects and altered oral bacteria »

  • enamel defects

  • increased risk of gingivitis

  • elevated risk of tooth decay

image showing considerations for oral health provision to those with CF

outline oral implications of sickle cell anaemia

• reduced enamel

• delayed tooth eruption

• ulceration risk

• changes in mandible structure can cause jaw pain 

how can gene expression be studied

• polymerase chain reaction

• RNA and DNA sequencing - bulk or single cell

• spatial transcriptomics/ proteomics - measures the gene expression of cells whilst preserving their location within a tissue

list therapeutic implications in relation to genetics

• genetic editing to correct defective genes

• detection of genetic changes

• stem cells to regenerate tissue

• precision dentistry

outline CRISPR

• allows precise editing of the genome

• developed by Jennifer Doudna and Emmanuelle Charpentier

how can genetic changes be detected 

• whole genome sequencing

• RNA sequencing

• DNA sequencing

• spatial transcriptomics

what are a good source of stem cells

• teeth - dental pulp stem cells

state areas of precision dentistry

• patient-specific care

• data-driven decision making

• outcome optimisation

precision dentistry: patient-specific care 

• tailoring dental diagnosis

• prevention and treatment based on an individual’s genetic, biological behavioural and environmental profile rather than relying on population-level averages

precision dentistry: data-driven decision making

• using advanced diagnostics, digital tools, biomarkers and AI to stratify risk, predict outcomes and guide targeted interventions

precision dentistry: outcome optimisation

• aiming to improve clinical effectiveness, reduce overtreatment and enhance patient experience through personalised, minimally invasive and predictive care pathways

what is a benefit of precision dentistry

• allows economic benefits »

• new tech is often initially expensive but gets cheaper overtime

• precision dentistry also eliminates other treatments that we know will not work for that patient

• not undertaking such tests/ treatments will save massive costs

what needs to be considered with precision dentistry

ethical considerations

• consent and data storage

• genetic discrimination risk

summary slide

B?

B?

C?

C?