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GENETICS IN

ORTHODONTICS
CONTENTS
• Introduction
• Nature versus nurture
• Basic definitions
• Heritability of dentofacial
• Structure of DNA. phenotypes
• From genes to proteins • Class II malocclusion
• Types of genetic effects and mode of • Class III malocclusion
inheritance • Hypodontia
• Regulation of gene expression • Ectopic eruption
• Signal transduction • Bilateral symmetry
• Craniofacial development • Exteral apical root
• Molecular regulation of development of resorption.
face • Craniofacial defects
• Signaling and growth factors • Cleft lip and palate
• Genetic control of craniofacial • Concepts of hereditary and
embryogenesis genetics in orthodontics
• Theories of growth control • Conclusion
• Heritability and its estimation • Bibliography
• Twin studies
• Familial study
INTRODUCTION

• Malocclusion is a manifestation of genetic and environmental interaction on the


development of the orofacial region.
• Consideration of genetic factors is important in understanding the cause of the
problem before attempting treatment.

 Orthodontics-Current Principles and Techniques 5th edition-Graber,Vanarsdall,Vig


Basic Definitions
• Chromatin is the substance that gives the nucleus a granular appearance,and is
observable in the nuclei of nondividing cells.

• Just before a cell undergoes division,the chromatin condenses to form discrete dark
staining bodies called chromosomes.

• Each chromosome comprises of two identical components.The two symmetrical halves


are called sister chromatids and they are attached together at a constricted region that
stains lightly and is called centromere.

• The centromere defines primary constriction of the chromosome and divides the
chromosome into a short arm and along arm.

 Medical genetics-3rd edition-Jorde,Carey,Bamshad,White.


 Genetics in dentistry-G.P.Pal,Niladri Kumar Mahato.
• Centromere play a pivotal role during the movement of chromosome during cell
division.

• An additional secondary constriction in one or both of chromatid and are linked to


the formation of nucleolus and hence referred nuclear organising region.-lie at the
distal end of the chromosome at the extreme end-called satelite.

 Genetics in dentistry-G.P.Pal,Niladri Kumar Mahato.


• Each human somatic cell contains 23 pairs of chromosome.
• One pair of chromosome is sex chromosome-XY chromosome.
• Other 22 pairs –autosomes.
• Somatic cell-diploid and human gametes-haploid.
• Chromosome contains genes.

 Medical genetics-3rd edition-Jorde,Carey,Bamshad,White


• A gene is defined as the entire DNA sequence necessary for the synthesis of a
functional polypeptide or RNA.

• It represent the smaller physical and functional units of inheritance that reside in
specific sites(loci)in the genome and are transmitted from parent to offsping.

• The genome contains the entire genetic content of a set of chromosome present
within a cell or an organism.

• Gene consists of DNA.

 Orthodontics-Current Principles and Techniques -5th edition-Graber,Vanarsdall,Vig


Structure of DNA.
• Three basic components:-
o pentose sugar,deoxyribose;
o a phosphate group
o 4 types of nitrogenous bases:
 adenine,guanine(purines)
 cytosine.,thymine(pyramidines).
• Double helix model:-DNA envisioned as a twisted ladder with chemical bonds.

• The two sides are composed of sugar and phosphate components,held together by phosphodiester bond.

• Projecting from each side at regular intervals are the nitrogenous bases.

• Base projecting from one side is bound to the base from other side by weak hydrogen bonds.

• Three hydrogen bonds between cytosine-guanosine pair.


• Two bonds between adenine-thymine pair.

 Medical genetics-3rd edition-Jorde,Carey,Bamshad,White


From Genes to Proteins
• While DNA is formed and replicated in the cell nucleus,protein synthesis takes place
in the cytoplasm.

• The information contained in DNA must be transported to the cytoplasm and then
used to dictate the composition of proteins.

• This involves two processes:-transcription and translation.

• The DNA code is transcribed into messenger RNA,which then leaves the nucleus to be
translated into proteins.

• Like DNA,RNA is composed of sugars,phosphate groups and nitrogenous bases.

• In case of RNA:-sugar is ribose instead of deoxyribose,uracil rather than


thymine,single strand instead of double strand.

 Medical genetics-3rd edition-Jorde,Carey,Bamshad,White


Transcription
• It is the process by which RNA sequence is formed from a DNA template.

• The type of RNA produced by the transcription process is termed messenger RNA(mRNA).

• To initiate mRNA transcription, RNA polymerase II binds to a promoter site on the DNA.

Gene Splicing
• The primary mRNA transcript is exactly complementary to the base sequence of the DNA template.

• In eukaryotes,sections of the RNA are removed by nuclear enzymes(introns),and the remaining


sections(exons) are spliced together to form the functional mRNA that will migrate to the cytoplasm.

• Introns form the major portion of most eukaryotic genes

 Medical genetics-3rd edition-Jorde,Carey,Bamshad,White


• The excised sequences are called introns and that are left to code for proteins are called exons.

• Only after gene splicing,mature transcript move out of the nucleus into the cytoplasm.

The Genetic Code


• Proteins are composed of one or more polypeptides,which are in turn composed of sequences of
aminoacids.

• Individual aminoacids are encoded by units of three mRNA bases,termed codons.

• There are 64 possible codons,3 signal the end of a gene-stop codons,UAA,UAG,UGA.

 Medical genetics-3rd edition-Jorde,Carey,Bamshad,White


Translation
• It is the process in which mRNA provides a template for the synthesis of a polypeptide.

• It interacts with molecules of tRNA which are cloverleaf-shaped RNA strands of about 80
nucleotides.

• Each tRNA molecule has a site at the 3’ end for the attachment of a specific amino acid by a covalent
bond.

• At the opposite end of the cloverleaf is a sequence of three nucleotides called the anticodon.

• The tRNA molecule picks up the aminoacid that is complementary to the anticodon sequence.

• Cytoplasmic site of protein synthesis is the ribosome,which consists of equal parts of enzymatic
proteins and ribosomal RNA(rRNA).

• The function of rRNA is to help bind mRNA and tRNA to the ribosome.

 Medical genetics-3rd edition-Jorde,Carey,Bamshad,White


• Genotype refers to the set of genes that an individual carries and in
particular usually refers to the particular pair of alleles (alternative forms
of a particular genes)that a person has at a given region of the genome.

• Phenotypes are observable properties,measureable features and physical


characteristics of an individual,as determined by the individual’s genotype
and the environment in which the individual develops over a period of
time.

Types of genetic effects and mode of inheritance


• A trait is a particular aspect or characteristic of the phenotype.

• Genetic influence include:monogenic,polygenic/multifactorial.

 Orthodontics-Current Principles and Techniques 5th edition-Graber,Vanarsdall,Vig


Mutations
• It is defined as a change in DNA sequence.It is the ultimate source of genetic variation.

• The principle types of mutation include:-


 Missense mutation:-produce a change in single aminoacid.

 Nonsense mutation:-produce one of the three stop codons(UAA,UAG,UGA) in the


messenger RNA.

 Frameshift mutation:-result from the addition or deletion of a number of bases that is


not a multiple of three.

 Promoter mutation:-decrease the affinity of RNA polymerase for a promoter


sitereduced production of mRNA.decreased production of a protein.

 Splice site mutation:-occur at intron-exon boundaries,alter splicing signal that is


necessary for proper excision of an intron.

 Medical genetics-3rd edition-Jorde,Carey,Bamshad,White


Monogenic Traits
• Traits that develop because of the influence of a single gene locus.

• Genes at the same locus on a pair of homologous chromosomes are alleles.

• When both the members of a pair of alleles are identical,the individual is homozygous for
that locus.

• When the two alleles at a specific locus are different,the individual is heterozygous for that
locus.
Autosomal dominant and recessive traits
• If having only one particular allele of the two alleles on a homologous pair of
autosomes(heterozygosity) is sufficient to lead to the production of the trait,the effect is
autosomal dominant.

• If production of the trait does not occur with only one particular allele of the two alleles on
an autosome,but does occur when both alleles are same(homozygosity),the effect is
autosomal recessive.

 Orthodontics-Current Principles and Techniques 5th edition-Graber,Vanarsdall,Vig


• The nature of the traits is studied by constructing family trees called
pedigrees in which males are denoted by square and females by circles.

Variable expressivity
• Although in each individual the trait is present,it may vary in its severity or
expression.

• Variable expressivity may also applied to the pleotopic effects of a


particular genotype;the expression of same gene may result in seemingly
disparate traits in an individual.

• The association of two or more traits together more often than what would
be expected by chance defines a syndrome.

 Orthodontics-Current Principles and Techniques 5th edition-Graber,Vanarsdall,Vig


• Variable expressivity in autosomal dominant phenotypes
associated with single gene mutation persumably resulted
from the interaction of different proteins from modifying gene
and environmental factors. Gene

Environmental Modifying
factors genes
Protein

Proteins

Phenotype
Autosomal recessive traits
• Concept of gene carrier is used with autosomal recessive trait.

• Carrier is heterozygous for a recessive gene.

• Parents of a child with autosomal recessive trait are typically


heterozygous(carriers).

• The rarer the recessive gene,the more likely it is that normal


parents who have an affected child will be blood relatives-
consanguineous.

 Orthodontics-Current Principles and Techniques 5th edition-Graber,Vanarsdall,Vig


X-linked Traits and Lyonisation
• Most of the genes on the X and Y chromosomes are not homologous and
are unequally distributed to males and females.

• Females who are heterozygous for the gene associated with the X linked
recessive phenotype may show some expression of the phenotype because
most of the genes on one of the X chromosomes in the female normally
get inactivated by a process called lyonisation.

• Lyonisation process starts early in development when each cell in the


female inactivates almost all of the genes on one of her two chromosomes.

 Orthodontics-Current Principles and Techniques 5th edition-Graber,Vanarsdall,Vig


Complex(polygenic/multifactorial)Trait

• Greater incidence compared to monogenic phenotypes.

• Polygenic term inferred the effect of multiple genes and enviromental factors on the
phenotype.

• A change in the phenotype depends on the result of the genetic and environmental
factors present at a given time.

• As polygenetic traits are influenced by environmental and multiple genetic factors,they


are also referred as multifactorial.

• Eg:-Nonsyndromic cleft lip-palate,neural tube defects such as spina bifida and


anencephaly,congenital hip dislocation.

 Orthodontics-Current Principles and Techniques 5th edition-Graber,Vanarsdall,Vig


Regulation of gene expression
• The process by which the inheritable information in a gene,DNA
sequence,is made into a functional gene product,such as protein or RNA is
known as gene expression.

• Gene regulation refers to the cellular control of the amount and timing of
changes in the appearance of the functional product of gene.

• Stages where gene expression is regulated are as follows:


 Chemical and structural modification of DNA or chromatin.
 Transcription
 Translation
 Post transcriptional modification
 RNA transport
 Post translational modification

 Textbook of craniofacial growth-Sridhar Premkumar


• Gene regulation is the basis for cellular differentiation,morphogenesis and adaptability
of any organism.

• It gives control over its structure and function.

• Proteins involved in regulating gene expression are called regulatory proteins2


types,activators or repressors

• Activators bind to switch a gene on and repressors bind to shut off a gene.

• Initiating the signal for gene regulation is achieved through the binding of some ligand to
a receptor.

• The receptors which are located both on the outside of the cell and on the inside of the
cell spanning the plasma membrane of the cell are called transmembrane receptors.

 Textbook of craniofacial growth-Sridhar Premkumar


Signal Transduction
• A signaling center or node is a cell group that regulates the behaviour of surrounding cells
by producing positive or negative intercellular signaling molecules.

• Growth factors stimulate cell proliferation and differentiation by acting through specific
receptors on responsive cells.

• Growth factors play analogous roles in embryogenesis,in the immune system,and during
inflammation and wound repair.

• Patterning of the development of regions,organs,and systems is controlled by genes


expressed as growth factor signaling molecules.

• The early development of a primitive streak(a rapidly proliferating elongating mass of cells
in the embryonic germ disk)demarcates initial distinction of embryonic tissues.

• A gene,Lim-1,for organisation of the primitive streak and for the development of entire
head.

 Craniofacial development-Geoffrey.H.Sperber.
Craniofacial development
Neural crest cells
• It is a transient component of the ectoderm,is located in between the neural tube and epidermis of
an embryo during neural tube formation.

• It is a highly pleuripotent cell population which plays critical role in the development of vertebrate
head.

• The facial mesenchyme is derived principally from the neural crest.

• Neural crest cells migrates extensively throughout the embryo in four overlapping
domains(cephalic,trunk,sacral and cardiac).

• Ectomesenchymal neural crest cells interact with epithelial and mesodermal population present
within the arches,leading to the formation of craniofacial bone,cartilage and connective tissue.

 Textbook of craniofacial growth-Sridhar Premkumar


Molecular regulation of development of face
• During the beginning of the 4th week of embryonic development of the face
is represented by stomatodeum situated beneath the devoloping brain.

• Surrounding structures of the face ultimately forms the face

• These structures are the frontonasal process,the medial and lateral nasal
process,the maxillary and mandibular process.

• All these facial process are covered by the ectoderm beneath which lies
mesoderm.

• Mesenchyme of the upper face comes from the neural crest cells from the
forebrain and midbrain areas while mandible from neural crest cells of
midbrain and hindbrain region.

 Genetics in dentistry-G.P.Pal,Niladri Kumar Mahato.


• Frontonasal process is formed bythe synthesis of retinoic acid in the ectodermal cells
covering the forebrain.Retinoic acid is responsible for the maintanence of the fibroblast
growth factor 8(FGF-8) signals and sonic hedgehog(SHH)signals.

• Growth of all these processes results from interactions between the overlying ectoderm
and underlying mesoderm.FGF-8 and Shh stimulate the growth of mesenchyme.

• The medial region of mandibular process responds to FGF-2 and FGF-4 local epithelial
signals and stimulates the growth of the underlying mesenchyme.

• Growth of lateral region of mandibular process is due to FGF-8 signals

• These signals are mediated by bone morphogenetic proteins Bmp-4 and Bmp-7 which are
produced in the lateral regions of the mandibular process.

• Dlx-1 and Dlx-2 expressed most proximally in the mandibular process;Dlx-5 and Dlx-6
more proximal;Dlx-3 and Dlx -7 most distally.

 Genetics in dentistry-G.P.Pal,Niladri Kumar Mahato.


Patterning the midline
• Sonic hedgehog are involved in the control of left-right assymetry,the determination of polarity in the
central nervous system,somites and limbs and in both organogenesis and formation of skeleton.

Role of homeobox genes


• A homeobox is a DNA sequence found within genes which are involved in the regulation of
development(morphogenesis).

• Genes that have a homeobox are called homeobox genes and form homeobox gene family.

• Regarded as master gene of the head and face controlling patterning,induction,programmed cell
death,and epithelial mesenchymal interaction during the development of the craniofacial complex.

• Genes of particular interest in the craniofacial development include:-


 HOX group,
 MSX 1 and MSX2(muscle segment)
 DLX(distal-less)
 OTX (orthodontical)
 GSC(goosecoid)
 SHH(Sonic hedgehog)

 Textbook of craniofacial growth-Sridhar Premkumar


Signaling and growth factors
Factors Abbrevation Derivation Action
Bone morphogenetic BMPs Pharyngeal Mesoderm induction;Dorso-ventral
protein arches:Frontonasal mass organiser;skeletogenesis;Neurogenesis
Bone derived BDNF Neural tube Stimulates dorsal root ganglia
neurotrophic factor
Distal-less Dlx Genome Transcriptional activator
Epidermal Growth Factor EGF Various organs;salivary Stimulatesproliferation and differentiation of
glands many cell types
Fibroblastic Growth FGFs Organs and organising Neural and mesodermal induction;stimulates
Factor centres proliferation of fibroblasts,
endothelium,myoblasts.osteoblasts
Hepatocyte growth HGF Pharyngeal aches Cranial motor axon growth;Angiogenesis
factor
Homeodomain proteins Hox-a,Hox- Genome Craniocaudal and dorsoventral patterning
b,Pax,Dlx
Insulin-like growth factor IGF 1 Sympathetic chain ganglia Stimulates proliferation of fat andconnective
1&2 IGF2 tissues and metabolism
Interleukin2 IL-2 White blood cells Stimulates proliferation of T-
Interleukin3 IL-3 lymphocytes;Hematopoetic growth factor;B
interleukin4 IL-4 cell growth factor
Lymphoid enhancer Lef1 Neural Regulates epithelial-mesenchymal
factor 1 crest;mesencephalon interactions
Sonic hedgehog Shh Various organs Neural plate and craniocaudal
patterning,chondrogenesis
Transriptional factors TFs Intermediate gene in Stimulates transcription
mesoderm induction of actin gene
cascade
Transforming growth TGF-α Various organs Promotes differentiation
factor-α of certain cells
Transforming growth TGF-β Various organs Mesoderm
factor -β induction;potentiates or
inhibits responses to
other growth factors

Craniofacial development-Geoffrey.H.Sperber
Genetic control of craniofacial embryogenesis
• The genetic control of craniofacial embryogenesis is via Hox genes which are responsible
for controlling morphogenesis of the regions of head and neck.

• Other homeobox containing genes which are expressed in the maxillary and mandibular
arches,and developing facial primordial are Msx-1,Msx-2.Dlx1-6,and Barx-1.

• Members of the Msx gene family,esp Msx-1 and Msx-2 are predominantly expressed in
the neural crest derived mesenchyme of the developing facial prominences.

• Goosecoid(Gsc) another homeobox containing transcription factor-play in craniofacial


development

• Other important genes include Otx(orthodontical),Shh(sonic hedgehog)and Indian


hedgehog(Ihh)

 Orthodontics-Diagnosis and management of malocclusion and dentofacial deformities-Om Prakash Kharbanda


• These homeobox genes act by exerting control on growth
factor family and the steroid/thyroid/retinoic acid super
family.

• The regulatory molecules in the mesenchyme,such as


FGF,ESF,TGF-α,TGF-β are the vehicles through which
homeobox gene information is expressed in the co-ordination
of cell migration and subsequent cell interactions which
regulate growth.

• Orthodontics-Diagnosis and management of malocclusion and dentofacial deformities-Om Prakash Kharbanda


Theories of growth control
• Three major theories
 Bone is the primary determinant of its own growth.
 Cartilage is the primary determinant of skeletal growth,while bone responds secondarily
and passively
 Soft tissue matrix in which the skeletal elements are embedded is the primary determinant
of growth,and both bone and cartilages are secondarily followers.

• The major difference in theories is the location at which genetic control is expressed.

• The first theory implies that genetic control is expressed directly at the level of bone;its locus should be the
periosteum

• Second or cartilage theory suggests the genetic control is expressed in cartilage while bone responds
passively being displaced

• Third theory assumes that genetic control is mediated to a large extend outside the skeletal system and that
growth of both bone and cartilage is controlled epigenetically occuring only in response to signal from other
tissues.

• Contemporary Orthodontics 5th edition-William.R.Proffitt.


Heritability and its estimation
• Twin studies
• The classic way to determine to what extent a characteristic is determined by
inheritance is to compare monozygotic(identical) with dizygotic(fraternal) twins.

• The scientific study of human twins began in the 1870s when Sir Francis Galton
published articles arguing that heredity is a strong factor than environment.

• Monozygotic twins occur because of early division of a fertilized egg, so each


individual has the same chromosomal DNA and the two are genetically identical.

• Any differences between them should be solely the result of environmental influences.

• Dizygotic twins occur when two eggs are released at the same time and fertilised by
different spermatozoa.

• They are not more similar than ordinary siblings,except that they share the same
intrauterine and family environment.

 Contemporary Orthodontics 5th edition-William.R.Proffitt.


 Textbook of craniofacial growth-Sridhar Premkumar
Limitations of twin study
• Difficult to obtain twin pairs for study.

• Difficult to establish zygosity and confirm the environments is same for both members of twin pair.

• Significance
• Well done twin studies-best way to evaluate heritability.

• Using twins with siblings as controls,Hudhes et al heriditary component for variation in spacing and
tooth position within the dental arches was 69% to 89%.It was 53% for overbite and only 28%for
overjet(greater environmental component than crowding,spacing/overbite).

• Corrucini and coworkers-appropriate corrections for unsuspected environmental differences within


twin pairs,the heritability of some of dental characteristics such as overjet is almost zero .

 Contemporary Orthodontics 5th edition-William.R.Proffitt.


Familial study
• Other classical method of estimating the influence of hereditary is to study
family members,observing similarities and differences between mother-
child,father-child,and sibling pairs.

• From an examination of cephalometric radiographs,heritability of


craniofacial(skeletal)characteristics was relatievely high but that of
dental(occlusal)characteristics was low.

• For skeletal characteristics,the heritability estimates increased with


increasing age.

• For dental characteristics,the heritability estimates decreased indicating an


increasing environmental contribution to the dental variation.

 Contemporary Orthodontics 5th edition-William.R.Proffitt.


Nature versus Nurture
• Neither genetic and epigenetic(environmental)factors alone are sufficient ,only their integrated
activities provide the necessary causes of growth and development.

• Dietary changes in modern societies, with increased consumption of soft, energy-rich food, has
resulted in less interproximal wear between the teeth.

• Research demonstrated this lack of attrition as a possible cause of malocclusion, particularly


crowding.

• A soft diet may also result in underdevelopment of the jaws and a lack of arch space, leading to
crowding.

• According to this hypothesis, hard diet requires vigorous mastication, stimulating the growth of
facial bones, particularly in the transverse dimension of the maxilla and mandible.

• Experimental studies have shown that dietary consistency and masticatory activity affect not
only the masticatory muscles, but also many aspects of bone growth, including bone size and
mass, internal bone structure, and craniofacial size and morphology.

 Handbook of orthodontics-Martyn.T.Cobourne &Andrew.T.Dibiase.


 Orthodontics-Current Principles and Techniques 5th edition-Graber,Vanarsdall,Vig.
HERITABILITY OF DENTOFACIAL PHENOTYPES

Malocclusions
• A malocclusion should be regarded as a developmental condition and does not represent
a single entity.

• It is the sum of a number of complex occlusal traits, which demonstrate multifactorial


inheritance.

• Although in certain cases specific factors and pathologies can be identified as the cause
of a malocclusion; in the majority, the aetiology is less clear.

• In each individual there is a close interaction between genetics and the environment
during development and growth of both the jaws and dentition; it is at this interface that
the aetiology of malocclusion lies .

 Handbook of orthodontics-Martyn.T.Cobourne &Andrew.T.Dibiase.


• The frequent presentation of malocclusion in patients with craniofacial birth defects also
supports a strong genetic etiology.

• About 150 genes/loci are associated with craniofacial conditions presenting


malocclusion.

• These genes represent molecular pathways to explore in malocclusion etiology.

• Recently, mouse studies showed that long-range transcriptional enhancers regulate the
expression of genes near and far during craniofacial development, resulting in subtle
differences in craniofacial shape.

• Thus, these enhancers could be a mechanism to explain dentofacial variations underlying


malocclusion.

 Orthodontics Craniofacial Research 2015 April;18(01):-Genetics of the dentofacial variation in human malocclusion.
• Genes implicated in bone (TGFB3, LTBP, IGF1, ENPP1) cartilage
development (Matrilin-1 and COL2A1), muscle function
(MYO1H and DUSP6) and tooth morphogenesis (EDA, XEDAR,
and BMP2), influence jaw and tooth size discrepancies.

 Orthodontics Craniofacial Research 2015 April;18(01):-Genetics of the


dentofacial variation in human malocclusion.
Class II Malocclusion
• Longitudinal studies indicated that Class II dentoskeletal characteristics can appear during the
primary dentition.
• Such discrepancies in general do not self-correct due to differences in growth magnitudes.
• The most recent study of Class II variation evaluated 309 Class II Caucasian adults explaining
81% of the variation.
• About half of this variation was depicted by vertical mandibular rotation, incisor angulations
and the size of the ramus and body of the mandible.

• Study shows higher correlation between the patient and his


immediate family supporting concept of polygenic inheritance for class II division I.

• Long face pattern of facial deformity-second most likely deformity to run in


families.
• Polygenic inheritance and autosomal dominance models, with incomplete penetrance and
variable expressivity, have been suggested for class II subdivision 1 and 2,
respectively

 Orthodontics Craniofacial Research 2015 April;18(01):-Genetics of the dentofacial variation in human malocclusion.
 Contemporary Orthodontics 5th edition-William.R.Proffitt.
 Textbook of craniofacial growth-Sridhar Premkumar
Class III malocclusion
• Mandibular prognathism referred as Hapsburg jaw.
• Although it is said to be multifactorial, in majority of cases it appears
to have autosomal dominant inheritance with incomplete penetrance
and investigators concluded there is a major gene that influences the expression
• Class III malocclusion features affect multiple craniofacial structures, appear early in
development, worsen with age.
• A recent study in 292 Caucasian adults which accounted for 81% of the phenotypic variation
recorded.
• About 54% of the variation was explained by the anterior–posterior (AP) position of the
mandible compared to the cranial base, the size of the maxillomandibular horizontal
discrepancy, and the lower incisor AP position.

 Orthodontics-Current Principles and Techniques 5th edition-Graber,Vanarsdall,Vig.

 Contemporary Orthodontics 5th edition-William.R.Proffitt.

 Orthodontics Craniofacial Research 2015 April;18(01):-Genetics of the dentofacial variation in human malocclusion.
• Positive correlations for mandibular prognathism include genes EPB41, MATN1,
SSX2IP, and PLXNA, Also positive associations have been found for genes COL2A1,
MYO1H, TGFB3, and LTBP2.

• Studies show that variants within DUSP6 could account for Class III malocclusion
due to maxillary hypoplasia subsequent to premature fusion of maxillary sutures.

 Orthodontics Craniofacial Research 2015 April;18(01):-Genetics of the dentofacial variation in human malocclusion.
HYPODONTIA
• Occur without a family history or as a part of a syndrome.

• Genetic factors are believed to play major role with


autosomal dominant,autosomal recessive,X-linked,and multifactorial inheritance.

• MSX1,PAX9,LTBP3 involved in nonsyndromic dominant hypodontia.

• Most common pattern of hypodontia involves maxillary lateral incisors.


• More common in permanent dentition.

• As food habits are more defined with change to selective pressure during chewing,there is
concominant reduction in tooth volume in the respective fields of incisors,premolars and molars.

• Therefore hypodontia involving third molars second premolars,lateral incisors are more
commonButler’s field theory.

 Contemporary Orthodontics 5th edition-William.R.Proffitt.


 Textbook of craniofacial growth-Sridhar Premkumar
Ectopic eruption
• If the single tooth is in the midline and symmetric with
normal crown and root shape and size, then it can be an
isolated finding or can be part of solitary median maxillary
cental incisor syndrome.

• This heterogenous condition include other midline developmental abnormalities of


the brain and other structures that can be due to mutation in the Sonic hedgehog
gene(SHH),SIX3 gene or genetic abnormality.

• Palatally placed ectopic canines are an inherited trait often occuring with missing
teeth,tooth size reduction and other ectopically placed tooth.

• Maxillary canine and 1st premolar transposition is the most common.

• Significant genetic component is the main cause of this common type of


transposition,there is familial occurrence,bilateral occurrence,and female
predominance.

 Orthodontics-Current Principles and Techniques 5th edition-Graber,Vanarsdall,Vig.


 Textbook of craniofacial growth-Sridhar Premkumar
Bilateral Symmetry
• 3 types of symmetry:-
 Directional assymetry:-when development of one side is different from that of
the other during normal development.
 Antisymmetry:-when one side is larger than the other,but which side is larger
varies in normal development and cannot be predicted before
development.less common than directional assymetry.
 Fluctuating assymetry:-when differences exists between right and left
side,with which side is larger being random.inability of an individual to develop
identical,bilateraaly homologous structures.
• Fluctuating assymetry observed in the primary and permanent dentition.
• Indirect measure of environmental stress so that difference between bilateral structures
are due predominantly to environmental factors
• Fluctuating assymetry is an indication of an individuals ability to cope with its
environment.
• Predominant source of occlusal variation is environmental,and experiementally been
associated with gene-gene interaction.

 Orthodontics-Current Principles and Techniques 5th edition-Graber,Vanarsdall,Vig.


External apical root resorption.
• The degree and severity of EARR associated with orthodontic
treatment are multifactorial ,involving host and environmental
factors.

• Individuals with bruxism,chronic nail biting and anterior open bites


with concomitant tongue thrust show an increased extent of EARR
before orthodontic treatment.

• Variation in interleukin-1β gene in orthodontically treated individuals


account for 15% of variation inEARR.

 Orthodontics-Current Principles and Techniques 5th edition-Graber,Vanarsdall,Vig.


Craniofacial Defects
Cleftlip and palate

• Half of the recognised syndromes associated with cleft lip and


palate are due to single gene disorders with equal distribution
between autosomal dominant and autosomal recessive.

• More males are born with cleft lip and palate and more
females have cleft palate alone.

• Incidence of cleft lip and palate is greatest in mongloid


population.

 Textbook of craniofacial growth-Sridhar Premkumar


• Studies of 3D facial soft tissue variation resulted in significant
associations between genes PRDM16, PAX3, TP63, C5orf50,
Col17A1, HMGA2, AJUBA, and ADK, and facial width and height.

• Genes and loci associated with oral clefts (IRF6, 8q24, SNAI1,
MSX1, ABCA4-ARHGAP29, and MAFB) were found to be associated
with normal facial variation and facial features within the cleft
phenotypic spectrum.

 Orthodontics Craniofacial Research 2015 April 18(01):-Genetics of the dentofacial


variation in human malocclusion.
Concepts of hereditary and genetics in orthodontics

• Orthodontic Era(1900-1930)
• Edward angle and his followers believed in what he referred to as “nature’s plan” for
the normal function and form of the occlusal plane.

• Angle influenced by Julius Wolff:-the form of a bone follows its function.

• He was influenced by Naturphilosophie:-nature is essentially a mystical power that


provides a blueprint for skeletal form,and that normal “function” is the process by
which nature ensured the genesis of normal form.

• Abnormal growth of the jaws leading to malocclusion and dentofacial deformity is not
inherited directly ,but results from abnormal function caused by ‘perverted’
behavioural habits and other external environmental conditions.

 American Journal of Orthodontics and Dentofacial Orthopedics 2015 Dec 148(6):-Evolving concepts of
hereditary and genetics.
• Angle asserted that orthodontic appliances can ‘unpervert’ forces on the
developing jaw and thereby stimulate normal growth of occlusal arches.

• Calvin Case relied on accepted scientific beliefs of the time about hereditary to
assert that the skeletal structures of the face and occlusal arches are inherited in
the final size and form through what he referred as biologic laws-meant Darwin’s
concept of pangenesis.

• American Journal of Orthodontics and Dentofacial Orthopedics 2015 Dec 148(6):-Evolving concepts of hereditary and
genetics.
Hereditary versus environment era(1930-1970)
• M.F Guyer provided the first discussion of Mendalian inheritance and use of the term
“genetics” in the AJO-DO in 1924.

• Theoretic basis for increased interest in the principles of hereditary and their potential
relevance for understanding malocclusion was summarized by Salzmann.

• In 1930s,German Orthodontist and Belgian physician introduced orthodontic community


to the idea developed in quantitative population genetics that the study of twins
provides a unique approach to separate the relative contribution of hereditary and
environment to physical constitution.

• Virtually all of these studies tended to support hereditary determines the size and shape
of the jaws in both normal and abnormal development and growth

 American Journal of Orthodontics and Dentofacial Orthopedics 2015 Dec 148(6):-Evolving concepts of hereditary
and genetics.
• By 1940s,hereditary factors are considered first in importance and local
environmental fators second in the process of growth and development.

Heritability era(1970-2000)
• The National Institute of Dental Research organised 2 workshops to review
the contemporary status of orthodontic research on the role of genetics in
malocclusion and occlusal variation.

• Beginning in the mid 1970s,a number of orthodontic researchers adopted


multivariate statical methods to study variability of specific metric features of
dentofacial complex to quantify proportionate degrees of genetic and
environmental contributions to dentofacial form.

• Advances in computer technologies permitted orthodontic researchers to


digitalise radiographic cephalograms and use multivariate statical methods to
explore patterns of craniometric variation in families,again with the goal of
providing more accurate predictions of dentofacial growth.

 American Journal of Orthodontics and Dentofacial Orthopedics 2015 Dec 148(6):-Evolving concepts of
hereditary and genetics.
• By mid 1980s,significant methodological problems in contemporary studies of
heritability overall had become apparent to several researchers.

• Studies of heritability with cephalometrics and measurement of occlusion even in twins


provide little direct information about underlying genetic mechanisms and didnot
address the possibility of altered genetic expression caused by functional and other
environmental factors.

• Melvin Moss,craniofacial biologist,developed functional matrix hypothesis as an evolving


conceptual framework that provided an alternative explanation to genetics for the
factors influencing development and growth of the craniofacial complex.

 American Journal of Orthodontics and Dentofacial Orthopedics 2015 Dec 148(6):-


Evolving concepts of hereditary and genetics.
Orthodontic Genomics era(2000-)
• The onset of orthodontic genomics era at the start of the 21st century
marked the start of a shift in orthodontic research,characterised most readily
by the rise of new prevailing questions and concerns abour genetic basis of
the specific molecular pathways underlying dentofacial development and
deformities.

• Despite the new focus on the molecular basis of development,analysis of


heritability through quantitative genetic remains important part of overall
research.

• The greatest progress took place in the identification of the genes for
craniofacial dysmorphologies,including growth factors and transcription
factors controlling morphogenesis and growth of craniofacial
tissues,candidate gene for midfacial deformities and genes affecting growth
of the condylar cartilage of the mandible both normally and during
treatment.

 American Journal of Orthodontics and Dentofacial Orthopedics 2015 Dec 148(6):-Evolving concepts of
hereditary and genetics.
CONCLUSION
• The interactions of genetic and environmental factors may account for the variability in expression of
malocclusion.

• The etiological complexity lies not only in unpredictable expression, but also in the wide spectrum of
dentofacial variation present in affected individuals.

• This complexity explains in part why most treatment approaches for malocclusion are directed to the
symptoms rather than to etiology.

• However, despite this complexity, the study of malocclusion etiology is fundamental to understanding
the biology underlying craniofacial growth and dental relations.

• Understanding the biology will aid progress toward effective treatment, prevention, thereby
decreasing the burden of this condition

 Orthodontics Craniofacial Research 2015 April;18(01):-Genetics of the dentofacial variation in human


malocclusion
BIBLIOGRAPHY
 Orthodontics-Current Principles and Techniques 5th edition-Graber,Vanarsdall,Vig.

 Contemporary Orthodontics 5th edition-William.R.Proffitt.

 Orthodontics Craniofacial Research 2015 April 18(01):-Genetics of the dentofacial variation in human
malocclusion.

 American Journal of Orthodontics and Dentofacial Orthopedics 2015 Dec 148(6):-Evolving concepts of
hereditary and genetics.

 Handbook of orthodontics-Martyn.T.Cobourne &Andrew.T.Dibiase.

 Craniofacial development-Geoffrey.H.Sperber

 Textbook of craniofacial growth-Sridhar Premkumar

 Orthodontics-Diagnosis and management of malocclusion and dentofacial deformities-Om Prakash Kharbanda

 Medical genetics-3rd edition-Jorde,Carey,Bamshad,White

 Genetics in dentistry-G.P.Pal,Niladri Kumar Mahato.

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