2. Content:
Introduction
History
Terminology
DNA
Genes
Mendelian genetics
Molecular genetics in oral and craniofacial morphology
Genetics in malocclusion
Conclusion
References
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3. Introduction
Growth is the combined result of interaction between several genetic and
environmental factors overtime.
Genetics is the science concerned with the structure and function of all
genes in different organisms.
The cell is the basic unit of any living body.
It is made of organelles such as cell wall, cytoplasm, endoplasmic
reticulum, ribosomes, mitochondria, and nucleus.
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5. The nucleus has thread-like structures of different length and shapes
called chromosomes.
The number of chromosomes in every cell of an organism is constant, and
it changes from one species to another.
All humans normally have 23 pairs of chromosomes as 22 pairs of
autosomes and one pair of sex chromosomes.
Females have two X chromosomes, while male has one X- and one Y-
chromosome.
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6. Gene is the smallest structural and functional unit of inheritance.
Genes have the ability to determine traits and undergo identical
replication and mutation.
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7. 7Genome is the entire genetic content of a set of chromosomes present
within a cell or organism.
The genome varies from one individual to another in terms of single
base changes of DNA as Single-nucleotide Polymorphisms (SNPs).
8. History
Austrian monk, Gregor John Mendel was known as “Father Of Modern
Genetics.”
The studies by Mendel, on garden pea, he put forward basic laws of
genetics, namely law of segregation, law of independent assortment,
and law of dominance.
In 1903, Sulton and Boveri proposed the “Chromosomal Theory of
Inheritance.”
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10. Thomas Hunt Morgan studied the arrangement of genes along
chromosomes.
In 1953, Watson and Crick demonstrated the structure of DNA
molecule.
Solenoid model of chromosome was proposed by Finch and Klung.
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12. Terminology 12
Autosome
A non-sex chromosome. Synonymous with somatic chromosomes (chromosome pairs
1-22).
Allele
An alternative form of a gene that occurs at the same locus on homologous
chromosomes
Chromosome
Rod-shaped structures within the cell nucleus that carry genes encoded by DNA.
Gene
A segment of a DNA molecule that codes for the synthesis of a single polypeptide.
13. Genome
Term used to denote the entire DNA sequence (gene content) of a gamete, person,
population, or species.
Genotype
All of the alleles present at the locus (or closely linked loci) of a blood group system,
indicating chromosomal alignment if appropriate, e.g., AO in the ABO
BGS, CDe/cde in the Rh BGS, or MS/Ns in the MNSs BGS. Genotypes are indicated
by superscripts, underlining, or italics.
DNA
Deoxyribonucleic acid. Composed of nucleic acids, these molecules encode the
genes that allow genetic information to be passed to offspring.
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14. Functional genes
Genes that produce proteins, e.g., blood group genes that produce antigens.
Dominant gene
A gene is dominant if it is expressed when heterozygous but its allele is not, e.g. in
the Lewis system the Le gene is dominant (expressed in
both Le Le and Le le genotypes) and the le gene is recessive.
Recessive gene
Genes are recessive if the phenotype that they code for is only expressed when the
genes are homozygous, e.g., le le genes, in the Lewis system or h h genes in the ABO
BGS
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15. Phenotype
The antigens (traits) that result from those genes that are directly expressed (can be
directly antigen typed), e.g., group A in the ABO BGS or D+C+E- c+e+ in the Rh
BGS.
Nucleic acids
Polymers of phosphorylated nucleosides, the building blocks of DNA and RNA.
Nucleoside
The building blocks of RNA and DNA. Compounds consisting of a purine (adenine
or guanine) or pyrimidine (thymine or cytosine) attached to ribose (in RNA) or
deoxyribose (in DNA) at the 11 carbon.
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16. Mutation
A permanent inheritable change in a single gene (point mutation) that results in
the existence of two or more alleles occurring at the same locus. Blood group
polymorphism has been caused by mutations occurring over long periods of
time.
Homozygous
The situation in which allelic genes are identical, e.g., the KK genotype or
the Fya Fya genotype.
Heterozygous
The situation in which allelic genes are different, e.g. the Kk genotype in the
Kell BGS or the Fya Fyb genotype in the Duffy BGS.
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17. D.N.A
De-oxy-ribonucleic acid contains the genetic instructions
used in development and functioning.
DNA is a long polymer of simple units called nucleotides.
It is a right handed double helix structure.
Nucleotides are made up of sugar and phosphate groups
joined by ester bonds(backbone).
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18. To each sugar one molecule of nucleotide bases is attached which are of 4 types.
The sequence of the bases decides the sequence of amino acid which in turn
decides the type of protein.
The four type of bases are-
1. Adenine
2. Guanine
3. Thiamine
4. Cytosine
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19. Transcription-
The process of formation of mRNA(messenger RNA) from DNA.
The nucleotide sequence of mRNA is complementary to DNA.
The enzyme catalyzing the reaction is RNA polymerase.
The RNA produced is known as primary transcript.
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20. Translation
The synthesis of new protein using mature mRNA as a template.
Ribosomes, proteins and transfer RNA(tRNA) are involved in translation.
tRNA contain unpaired bases complementary to mRNA called anticodon on
one side and an amino acid on other.
The ribosome ligates the amino-acid to form a new polypeptide chain.
The new protein achieves a 3D structure to obtain functional competency.
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22. Gene-The unit of inheritance.
Gene is a long strand of DNA which contains 3 parts-
1. Promoter
2. Coding sequence
3. Non-coding sequence
Promoter controls gene activity and the other two are involved in
transcription.
Gene that encode protein are in a sequence of three nucleotides called
codons. Each codon codes for each amino acid.
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23. Regulation of gene expression-
The formation of functional gene products like RNA or proteins is called
gene expression.
The cellular control of the amount and timing of changes in the
appearance of gene product is gene regulation.
Gene regulation is the basis for cellular differentiation, morphogenesis
and versatility and adaptability of organism.
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24. The stages where gene expression is regulated are-
1. Chemical or structural modification of DNA or chromatin
2. Transcription
3. Translation
4. Post transcription modification
5. RNA transport
6. mRNA degradation
7. Post translational modification
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25. Regulatory proteins are of two types-
1. Activators- switch on a gene
2. Repressors- shut off a gene
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26. 26 Gene regulation respond in two ways-
1. Inducible system- it is off unless there is presence of some
molecule(inducer) which allows for gene expression.
2. Repressible system- it suppresses the gene expression only if there is a
presence of some molecule(corepressor).
27. Up regulation-
The increase in gene expression occurring due to trigger signal
originating internal or external of the cell.
Eg. Deficiency of some receptor protein.
Down regulation-
The process resulting in reduced gene expression and corresponding
protein expression.
Eg. When a cell is overly stimulated by neurotransmitter, hormone or
drug and receptor protein expression is decreased to protect the cell
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28. Mutations
Alteration in the base sequence of a particular gene.
The error rate per site is only around 10-6 to 10-10 in eukaryotes.
The cell contain many repair mechanism for preventing mutation and
maintaining the integrity of the genome.
If mutation occur during gametogenesis, it effects cell throughout the body.
If mutations occur after fertilization, then only a proportion of cells will be
effected, i.e., somatic mutation.
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30. Mendelian genetics
Mendel was the first to suggest the existence of genes.
Two copies of each gene is present.
Alleles are different form of genes which give rise to different
phenotypes.
1. Homozygous- identical copies of genes
2. Heterozygous- both copies different from each other
Alleles may be dominant or recessive.
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31. Mendel’s Law
Law of uniformity-
When homozygous of different alleles are crossed all the off-springs of
1st generation are identical and heterozygous.
Law of segregation-
1. Alternative version of genes accounts for variations.
2. For each characteristics, an organism inherits two alleles one from
each parent.
3. Each gamete will contain only one allele for each gene(segregation).
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32. Law of independent assortment- Inheritance law.
Inheritance pattern of one trait will not effect the inheritance pattern other.
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33. Molecular genetics in oral and craniofacial
morphology
The craniofacial complex is the result of chain of biochemical reaction
regulated presumably by genes.
Homeobox containing genes are expressed in maxillary and mandibular
arches and developing facial primordia. Theses genes include-
Msx1
Msx 2
Dlx1-6
Barx 1
Theses genes perform essential roles during the development of facial
complex.
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35. Members of Msx family are strongly
expressed in neural crest derived
mesenchyme of the developing facial
prominence.
Members of multigene dlx family are
expressed in the complex pattern within the
embryonic ectoderm and mesenchyme of
maxillary and mandibular process.
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36. Goosecoid gene is also a homeobox containing gene which involve in
essential inductive tissue interactions during the formation of the head.
Sonic-hedgehog(Shh)are involved in control of left right assymmertry,
polarity of central nervous system.
Later in development Shh is expressed in the ectoderm of frontonasal and
maxillary processes.
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38. Genetics in malocclusion
Craniofacial disorders and genetic etiology with malocclusion
Heritability estimates of craniofacial skeletal structures are greater
than those for dentoalveolar traits.
Skeletal malocclusions are more influenced by genetics whereas
dental malocclusions are more often due to environmental factors.
Class II division 1 and class II division 2 malocclusions are
multifactorial while class III malocclusion is heavily influenced by
genetics.
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39. Class II division 1 malocclusion
• Class II division I malocclusion appears to have a
polygenic/multifactorial inheritance.
• Environmental factors, such as tongue pressure, digit sucking
habit can also contribute to class II division 1 malocclusion.
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40. Class II division 2 malocclusion
• Class II division 2 malocclusion exhibits high genetic influence and is often
considered as a genetic trait.
• There is 100% concordance of class ii division 2 malocclusion in monozygotic
twin pair giving a strong evidence for genetics as main ethological factor in
development of class ii division 2 malocclusion.
• It is possibly a autosomal dominant inheritance with incomplete penetrance.
• High lip line, lip morphology and behavior are also considered to be causing
class ii division 2 malocclusion.
• Simultaneous and synergistic influence of genetics and environment
(multifactorial inheritance) is attributed to the development of class ii division 2
malocclusion.
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41. Class III malocclusion-
• The most famous example of a genetic trait in humans passing through
several generations is probably the pedigree of the so called “hapsburg
jaw.”
• This was the famous mandibular prognathism demonstrated by several
generations of the Hungarian/Austrian dual monarchy.
• Mandibular prognathism was an autosomal dominant trait.
• Various environmental factors, such as enlarged tonsils, nasal blockage,
posture, premature loss of permanent molars due to trauma can also
cause class iii malocclusion, the overall inheritance pattern best fits an
autosomal dominant model.
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42. Class I Malocclusion with crowding
EDA (Ectodysplasin) gene associated with crowding act in a
morphogenetic role in teeth and other ectodermal organs. Example, teeth,
hair, and sweat glands.
Mutations in the EDA gene:
Defects in ectodermal organs.
Mutations results in differential gene expression which causes large tooth
phenotype.
This ultimately results in crowding.
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43. Ectopic maxillary canines:
Palatally ectopic canines are an inherited trait.
Being a complex of genetically related dental disturbances often occur
in combination with missing teeth, teeth size reduction, supernumerary
teeth and other ectopically positioned teeth
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44. Deep bite, open bite:
The study showed that deep bite in males and open bite in females had
concordance only in mz twin-pairs.
Arch dimensions:
Arch size, cross bite-arch breadth discrepancy showed high heritability
heritability: 27 % genetic and 73 % environmental.
There is genetic control of first molar mesiodistal relationship, overjet,
overbite, tooth rotations.
Heredity played a significant role in determining the factors such as – width
and length of dental arch, crowding, spacing of teeth and degree of
overbite.
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45. Orofacial clefts:
Prevalence of 1 to 2 per 1000 live births.
Two different phenotypes are:
(1) cleft lip with or without cleft palate (CL/P)
(2) cleft palate only (CPO)
o Syndromic forms of CL/P:
Simple Mendelian inheritance patterns.
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46. o Van der woude syndrome:
Autosomal dominant form of orofacial clefting.
Prevalence of 1 per 34,000 live births.
Gene localized by mapping to long arm of chromosome 1, 1q32q41.
Mutation in the interferon regulatory factor 6 (IRF6) gene, IRF6: medial
edge epithelia of palatal shelves.
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47. CL/P ectodermal dysplasia syndrome:
A rare autosomal recessive trait.
Gene mapped on chromosome 11.
Mutations identified in the poliovirus receptor-like 1 (PVRL1)
gene.
PVRL1: expressed in the epithelia of the palatal shelves, nose
and skin, as well as the dental ectoderm.
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48. X-linked cleft palate and ankyloglossia:
An X-linked recessive pattern on the long arm of chromosome X.
Gene was identified as TBX22 which is expressed in the palatal
shelves and tongue during development.
If a male inherits a mutated TBX22 it is highly likely that he will
have the disease since this is the only copy of the TBX22 gene.
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49. Genetics of non-syndromic CL/P:
Genetically complex trait: Majority have no family history.
Evaluation of inheritance patterns: not revealed a simple Mendelian
mode of inheritance.
Greater concordance in MZ compared with DZ twins.
Concordance rate in MZ is only 40% to 60%, suggesting the influence
of environmental factors is also important.
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50. High association between IRF6 variants, MSX1 and CL/P .
MSX1 is involved in both primary and secondary palatogenesis.
MSX1 inactivation results in cleft palate and tooth agenesis.
Mutations in MSX1 in 2% of patients with nonsyndromic clefting.
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51. Conclusion
• Malocclusion with a “genetic cause” is generally thought to be less
amenable to treatment than those with an “environmental cause”. The
greater the genetic component, the worse the prognosis for a successful
outcome by means of orthodontic intervention.
• In recent times, malocclusions of genetic origin (skeletal discrepancies)
when detected in growing period, are being successfully treated using
orthopedic and functional appliances, except in extreme cases where
surgical intervention is required.
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52. • When malocclusion is primarily of genetic origin, for example, severe
mandibular prognathism then treatment will be palliative or surgical.
Information regarding the treatment need for a child and treatment can
be begun at an early age.
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53. References
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Oxford University Press, 2002.
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5. Morton NE. Genetic epidemiology. Ann Rev Genet. 1993; 27:523-38.
6. Sandler I. Development. Mendel’s legacy to genetics. Genetics. 2000; 154(1):7-11.
7. Niswander JD. Genetics of common dental disorders. Dent Clin North Am. 1975; 19(1):197-
206.
8. Proffit WR, Fields HW, Sarver DM. Contemporary Orthodontics. 5th edition. Saint Louis:
Mosby, 2013, 131-3.
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