genetic disorders in dentistry Flashcards
What is epigenetics?
Determines how genes are read
Stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence
Heritable, self-perpetuating and reversible
DNA methylation, histone modification, nucleosome location or non-coding RNA
Low levels of certain nutrients/toxins can affect the enzymes that methylated DNA
What is a transepigenetic signal?
Transcription factor
Activates it’s own transcription so epigenetic state is self sustains
- Small RNAs can act as trans signal
- Cis signals are physically associated w DNA eg. DNA methylation
How is DNA methylation linked with disease?
Silences genes by blocking the binding of other proteins so interfering w transcription
Abnormal methylation has been demonstrated in Fragile X syndrome
Cancer cells- low levels of methylation- inappropriate activation/genes switch off controlling cell division
How are genes involved in tooth development?
Highly controlled and coordinated interaction between cells of different embryonic origins
Tooth morphology- position in mouth and combination of genes expressed in area
Tooth initiation/patterning- genetic pathways
Growth factors control the expression of genes- can be reversed
Mutation in PAX9 is associated w oligodontia
Novel cleft susceptibility genes in chromosome 6q
What is a gene problem that affects the oral cavity?
Ectodermal dysplasia- 150 clinically distinct hereditary syndromes, defects in morphogenesis of ectodermal structures (teeth, nails, hair, skin)
What has genetics got to do with caries?
Need more date
GWAS- examine genome-wide set of genetic variants in different people to see if any variant is associated with a trait
What are taste genes?
Bitter taste receptor- TAS2R38
Sweet taste receptor- TAS1R2
What genes affect tooth development?
Amelogenin- AMELX
Ameloblastin- AMBN
Tuftelin- TUFT1
What genes affect salivary function?
Acid proline-rich proteins- PRH1
Carbonic anhydrase 6- CAB6
What is amelogenesis imperfecta?
Group of developmental conditions that affect structure and clinical appearance of enamel
May be associated w systemic changes
Isolated or part of syndrome
Amelogenin- most abundant enamel matrix protein and multiple isoforms due to alternative splicing in AMELX exon 4
Silent mutation means it’s included in mRNA transcript
What are advantages of salivary glands?
- Well encapsulated
- Luminal membrane in most epithelial cells easy to access and non invasive
- Ductal access uses limited volume so low vector doses can be used
- Epithelial cells- well differentiated and slow dividing- stable
- Make large amounts of protein for export (endo/exocrine)
- Not crucial for life so one can be removed if need be
How is protein secreted from the salivary gland?
Saliva- mucosal- across apical membrane
Constitutive leading mainly towards interstitium and circulation- serosa- across basolateral membrane
Overexpression= overflow exits vi constitutive into circulation
