GENETICS AND ITS ROLE IN
ORTHODONTICS
www.indiandentalacademy.com
INDIAN DENTAL ACADEMY
Leader in continuing dental educat...
CONTENTS
 INTRODUCTION
 DEFINITIONS
 MENDELISM
 HUMAN CHROMOSOME
 MODES OF INHERITANCE
 monogenic
 multifactorial
...
Orthodontics and genetics
 Malocclusion is a manifestation of genetic
and environmental interaction on the
development of...
 Determination of the actual level of genetic
contribution - significant effect on prognosis
& treatment planning.
 If m...
 So it is important to find out whether
malocclusion is under genetic or
environmental influences.
www.indiandentalacadem...
Terms
Genetics -
• The branch of biology which deals primarily
with the principles of heredity & variation &
secondarily w...
Heredity -
• It can be defined as that force of nature which
permits the transmission of characteristics of a
species from...
 Chromatin - it is the name given to the material of
which chromosomes are made
 Gene - is a part of DNA molecule which ...
 Autosome- is any chromosome other than the sex
chromosome.
 Genotype - genetic constitution of an individual
 Phenotyp...
 Trait - any detectable phenotypic property or
character.
 Linkage - two genes situated close together
on same chromosom...
 Heritability-proportion of the phenotypic
variance attributable to genotype.
 Genome- contains the entire genetic conte...
 Multifactorial inheritance- if the genetic
variation of a particular phenotypic trait is
dependent on the simultaneous s...
Development of genetics
 Mendelism - Gregor Johann Mendel.
 He made his discoveries by analysis of results after
crossin...
In his monohybrid experiments he found the genotypic
ratio of 1 when he crossed pure varieties with
opposing traits.
R R
r...
R r
R RR Rr
r Rr rr
Crossing the second generation in which he obtained
plants with only round seeds , he obtained genotyp...
Dihybrid cross:
When he crossed the second generation of plant variable in two
characteristics he obtained a phenotypic ra...
Mendel’s laws:
 First law-a unit of genetic information is
transmissible unchanged from generation to
generation.
 Secon...
 Third law or Law of Independent assortment –
independent assortment occurs only when genes
affecting different character...
 Law of Uniformity –when 2 homozygotes with
different alleles are crossed all of the off springs of
first generation are ...
Human chromosome
 These are thread like structures located in the cell
nucleus.
 Each species has a specific number of c...
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 Individual chromosomes differ not only in position of
centromere but also in their overall length(amount of
DNA )
 Huma...
Centromere
Middle
Off center
If close to the end
At one terminal end
tip
Name
Metacentric
Sub metacentric
Acrocentric(in t...
Group chromosome description
A 1-3 Largest ;1&3 mc,2sc
B 4-5 Large ;sc
C 6-12 &X Medium size;sc
D 13-15 Medium size;ac wit...
Modes of inheritance
 Population genetics deals with the study of mode of
inheritance of traits and distribution of genes...
 All human beings normally have 22 homologous
pairs of chromosomes called autosomes that are
numbered by size and other c...
 When both members of a pair of alleles are
identical, the individual is homozygous for
that locus.
 When the two allele...
 Exception to this- gametes contain only
single representative of each pair of
chromosomes.
 When 2 gametes join at fert...
Monogenic Traits
 Traits that develop because of the influence
of a single gene locus are monogenic.
 Also called as men...
Autosomal dominant traits and
penetrance
 If having only one particular allele of the two alleles
on a homologous pair of...
 The trait (phenotype) is dominant or
recessive and not the gene itself.
 The nature of the traits is studied by
constru...
 The study of multiple families will yield the following
criteria for autosomal dominant inheritance:
(1) The trait occur...
(3) if an individual has the gene that results in the trait,
each child has a 50% chance of inheriting the gene
that leads...
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 Exceptions to this will be seen in-
 Trait showing nonpenetrance in a particular
offspring.
 A new mutation occurred i...
Penetrance
 When a person with a given genotype fails
to demonstrate the trait characteristic for the
genotype, the trait...
Variable expressivity
 In each individual the trait is present or not
when discussing penetrance, if the trait is
present...
 For example, osteogenesis imperfecta involving type
I collagen
 abnormalities.
(1) multiple fractures
(2) blue sclera
(...
Autosomal recessive traits
 If production of the trait does not occur with only one
particular allele of the two alleles ...
 Parents of a child with the autosomal
recessive trait are typically heterozygous
(carriers) and most often are diagnosed...
 In autosomal recessive traits, the following
three gene pairs are found:
 AA-homozygous, not showing the trait or
being...
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X-linked traits and Iyonization
 Most of the genes on the X and Y chromosomes are
not homologous and are unequally distri...
 A normally functioning homologous allele is not
present on another chromosome, recessive genes
on the one male X chromos...
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 Full expression of rare X-linked recessive
phenotypes is almost completely restricted to
males, and occasionally it is s...
 The lyonization process starts early in
development when each cell in the female
inactivates almost all of the genes on ...
Lyon hypothesis
 In the female all or most of one X chromosome is
genetically inactive and forms Barr body.
 Decision wh...
 There are phenotypes that "run in families" but do not
adhere to patterns of mendelian inheritance.
 These are referred...
 Multifactorial inheritance- trait is determined
by the interaction of a number of genes at
different loci, each with a s...
 multifactorial =polygenic + environmental
 A change in phenotype depends on the result of the
genetic and environmental...
 Examples of polygenic traits include height
and intelligence quotient, both of which are
continuous traits greatly influ...
Discontinuous multifactorial traits
 This describes the traits determined by
multiple gene loci which are present or
abse...
 The accepted explanation of discontinuous
multifactorial variation rests on the
assumption that there is an underlying s...
 The condition is present only when the
liability exceeds a critical threshold value,and
the greater the level of liabili...
 Cleft lip and palate is a congenital
malformation inherited as a multifactorial
trait.
 In the mildest form the lip alo...
 The parents of a cleft lip and palate patient
are often unaffected, and there may be no
family history of cleft lip and ...
 The parents must have sufficient normally
active genes to have normally formed lips
and palates. Only when the balance e...
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 Liability curve shifts to right for first degree
relatives.
 More severe the malformation- liability curve
shifts to ri...
 Some multifactorial traits show an unequal sex ratio.
 Incidence is increased in the relatives of affected
females.
 T...
Continuous multifactorial traits
 Many normal human characteristics are
determined as continuous multifactorial traits.
T...
 For example - height.
- malocclusion
Not an abnormality or disease but a variation of
occlusion in a continuous multifac...
Etiologic heterogeneity
 Both continuous &discontinuous variation have a
multifactorial basis so that different patients ...
Twin studies
 Twin studies are useful in study of population
genetics.
 To determine the role of genetic and
environment...
 Dizygotic /fraternal
twins –they develop
from two different
embryos
 Genetically alike like
any other siblings
 Can be...
Various methods have been used to differentiate
 Hair&eye color
 Ear form
 Teeth morphology
 Phenylthiocarbamide taste...
Concordance & Discordance
 Twins are concordant if they both show a
discontinuous trait and discordant if only one
shows ...
 Monozygotic twins have similar genotypes
 Dizygotic twins are like siblings.
 If a condition has no genetic component
...
 For a single-gene trait or a chromosomal disorder
the monozygotic concordance rate will be 100%,
whereas the dizygotic r...
 In cleft studies, the monozygotic twin concordance
rate for cleft lip and palate and cleft palate is 35 and
26 per cent,...
Twin studies for occlusal & dentofacial
structures
• Lundstorm (1948)-concluded that genetic factors
have greater influenc...
• Krupanidhi &V.Surendra Shetty(1989)-assessed
amount of genetic &environmental influence on
dental measurements in twins
...
 Ferguson –Smith(1993) cleft study ,the
monozygotic twin concordance rate for CLP&
CP was 35 &26 % respectively dizygotic...
Mutations
A mutation is defined as an alteration or
change in genetic material .
Mutations are due to
 Mutagenic factors ...
 main groups of chemicals which,cause mutation are-
 Base analogues which mimic standard bases, but
pair improperly (e.g...
 Mutations can be coded or noncoded .
 Coded are the once that are transmitted.
 Mutations of the somatic cells cannot ...
 In a point mutation a single nucleotide base
is replaced by a different nucleotide base.
 transition –purine to purine
...
 Synonyms –mutations does not alter the
polypeptide product of gene also called
silent.
 Non synonymous –mutations lead ...
 Missense –a simple base pair substitution
can result in coding for a different amimoacid
and synthesis of altered protei...
Deletion/insertion
 Deletion is the loss of 1 or more nucleotides
 Insertion is the addition of 1 or more
nucleotides
 ...
 The majority of mutations are likely to cause reduced
fitness ,a reduced ability of the resulting zygote to
contribute p...
Chromosomal aberrations
 Alterations of the genetic material which
involves many genes & large amount of DNA
1. Numerical...
1. Numerical aberrations
 Euploidy –triploidy,tetraploidy
 Aneuploidy –monosomies,trisomies
tetrasomies
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Structural aberrations
 Translocations –transfer of genetic material from one
chromosome to another
 Inversions –rearran...
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Chromosome abnormality
 13 trisomy---Patau’s
Mental retardation
Microcephaly
Cleft lip/palate
Micrognathia,small eyes
 1...
 XO ---Turners
Retarded growth
Micrognathia
Spade like chest
Ovarian agenesis
 21 trisomy --Down’s
Brachycephaly
Mental ...
 XXY--Klinefelter’s
Gynecomastia
Small testes
Decreased facial hair
 4p- Wolf-hirchhorn
Mental retardation
Abnormal faci...
Role of neural crest cells
 To understand genetic mechanisms
involved in craniofacial morphogenesis at
the molecular leve...
 Facial development in the embryo is demarcated by
the appearance of the pre-chordal plate (the cranial
end of the embryo...
 During their migration they undergo a number of
interactions with the extra-cellular matrix, and with
adjacent epithelia...
 Neural crest cell migration and the factors that cause these
cells to localise in particular regions is not yet complete...
The role of cell adhesion molecules
 cell adhesion molecules such as cadherins,
integrins, immunoglobulins, and proteogly...
Homeobox genes
 Homeobox genes are genes which are highly
conserved through out evolution of diverse
organisms and are no...
Genes of particular interest in craniofacial
developmemt are:
 Hox group
 Msx 1&Msx 2(muscle segment)
 Dlx (distalless)...
Proteins encoded by these homeobox genes are
transcription factors which control transcription of
RNA from the DNA templat...
At a cellular level this control is expressed through two
main groups of regulatory proteins
- growth factor family
-stero...
 These regulatory molecules in the mesenchyme
such as
 fibroblast growth factor (FGF)
 epidermal growth factor (EGF)
 ...
 By this means different parts of the DNA are
activated in different cells regulating the different
proteins ,enzymes .et...
Molecular genetics in oral and craniofacial
dysmorphology
 Mutations in fibroblast growth factor- affect suture
developme...
 mutation of core binding factor I gene:
Cleidocranial dysplasia
 mutation of long arm of chromosome 5
Treacher Collins ...
Molecular genetics in dental development
 Role in epithelial and mesenchymal
interaction
 Bone morphogenetic proteins-2,...
Control of tooth development
 Muscle specific homeobox genes Msx-l and Msx-2 are
involved in epithelial and mesenchymal i...
Disorders of tooth development
 Amelogenesis imperfecta
 It is a group of genetically heterogeneous disorders
affecting ...
 In 1997 MacDoughall et al mapped the ameloblastin
gene within critical region for autosomal dominant AI
at chromosome 4q...
Dentinogenesis imperfecta
 It is autosomal dominant
 Occurs in about 1:8000 live birth
 Presents with brownish discolor...
Hypodontia
 Msx 1 is strongly expressed in dental mesenchyme
throughout the bud ,cap &bell stages of
odontogenesis
 Vast...
 Genetic factors are believed to play a major role in
most of the cases of hypodontia with autosomal
dominant, autosomal ...
Peg shaped laterals
 This can be an autosomal dominant trait with
incomplete penetrance and variable expressivity as
evid...
Ectodermal dysplasia
 Hypohidrotic ectodermal dysplasia is a
heterogeneous disorder with clinically many distinct
types
...
solitary median maxillary central
incisor syndrome
 The presence of a single primary and permanent
maxillary incisor whic...
Genetic influence on tooth number
,size,morphology,position,& eruption
 Msx 1 &Msx 2 are responsible for stability in den...
Supernumerary teeth
 Brook (1974) reported that prevalence of
supernumerary teeth in British school children was
2.1%in p...
Abnormal tooth shape
 Alvesalo &Portin (1969) provided substantial
evidence supporting the view that missing
,malformed l...
Ectopic maxillary canines
 Peck et al (1994) concluded that palatally ectopic
canines were an inherited trait ,being one ...
Submerged primary molars
 It occurs most commonly in mandibular arch ,there is
a high rate of concordance between the mon...
Maxillary midline diastema
 Numerous etiologies have been proposed –toothsize
arch length discrepancy ,aberrant labial fr...
 Class II div 1 malocclusion –study done by Harris
(1975) show a higher correlation coefficient between
patient & his imm...
 Class II div 2 malocclusion –it is a distinct clinical
entity & is a more consistent collection of definable
morphometri...
 In study done on twins ,there was 100% concordance
for class II div 2 among monozygotic twins &90 %
dizygotic twins were...
 Class III malocclusion-the most famous example of
a genetic trait in humans passing through several
generations is the p...
 Strohmayer (1937) did a detail pedigree analysis &
found out that it was a autosomal dominant
trait,other studies found ...
ENVIRONMENTAL AND GENETIC INFLUENCES ON
BILATERAL SYMMETRY
 Three types of asymmetry:
 Directional
 Antisymmetry
 Fluc...
 Directional asymmetry occurs when development of
one side is different from that of the other during
normal development....
 Antisymmetry occurs when one side is larger than
the other, but which side is larger is variable in
normal development a...
 The third type of asymmetry, fluctuating, occurs
when a difference exists between right and left sides,
with which side ...
 Fluctuating asymmetry has been observed in the
primary and permanent dentitions.
 The greater amount of fluctuating asy...
GENETIC FACTORS AND EXTERNAL
APICAL ROOT RESORPTION
 The degree and severity of external apical root
resorption associate...
 Variation in the interleukin-lb gene (IL-l B) in
orthodontically treated individuals accounts for 15%
of the variation i...
Role of epigenetic factors
 Etiology of malocclusion
genetic environmental
 More important is to understand the interact...
 The influence of genetics on dentofacial
morphology does not imply that genetic
information is solely located in bones ,...
 Mastication ,speech ,facial expression & swallowing
are examples of neuromuscular patterns .
 Although they are under c...
 Although the bones are also influenced by functional
matrix, the functional matrix comprises of
neuromuscular activity w...
Human genome project
 Begun formally in 1990, the U.S. Human Genome
Project is a 13-year effort coordinated by the U.S.
D...
 Determine the sequences of the 3 billion chemical
base pairs that make up human DNA.
 identify all the approximate 30,0...
The Oral &Craniofacial genome project seeks to set up
collaborative laboratory research projects on human
&mouse embryonic...
Conclusion
 Contrary to the presumption that malocclusions of
"genetic cause" are less amenable to treatment than
those o...
 In the future, orthodontists ability to treat
patients better will depend on investigations
into how environmental facto...
We used to think that our fate is in stars
Now we know that in large measure it is in our
GENES.
For more details please v...
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Genetics and orthodontics /certified fixed orthodontic courses by Indian dental academy

  1. 1. GENETICS AND ITS ROLE IN ORTHODONTICS www.indiandentalacademy.com INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com
  2. 2. CONTENTS  INTRODUCTION  DEFINITIONS  MENDELISM  HUMAN CHROMOSOME  MODES OF INHERITANCE  monogenic  multifactorial  TWIN STUDIES  MUTATIONS  CHROMOSOMAL ABNORMALITIES  ROLE OF GENES IN MALOCCLUSION www.indiandentalacademy.com
  3. 3. Orthodontics and genetics  Malocclusion is a manifestation of genetic and environmental interaction on the development of the orofacial region.  Orthodontists are interested in genetics to understand why a patient has a particular occlusion. www.indiandentalacademy.com
  4. 4.  Determination of the actual level of genetic contribution - significant effect on prognosis & treatment planning.  If malocclusion is a genetically controlled phenomenon- only genetic counseling & early intervention with appliances may be of some help. www.indiandentalacademy.com
  5. 5.  So it is important to find out whether malocclusion is under genetic or environmental influences. www.indiandentalacademy.com
  6. 6. Terms Genetics - • The branch of biology which deals primarily with the principles of heredity & variation & secondarily with the role of environmental factors as they interact with genes in the development of an individual. www.indiandentalacademy.com
  7. 7. Heredity - • It can be defined as that force of nature which permits the transmission of characteristics of a species from generation to generation .  Gamete - a germ cell (sperm or ovum ) containing haploid number of chromosomes .  Chromosomes - thread like deep staining bodies situated within nucleus www.indiandentalacademy.com
  8. 8.  Chromatin - it is the name given to the material of which chromosomes are made  Gene - is a part of DNA molecule which directs the synthesis of specific polypeptide chain.  Allele- alternative forms of a gene found at same locus on homologous chromosomes. www.indiandentalacademy.com
  9. 9.  Autosome- is any chromosome other than the sex chromosome.  Genotype - genetic constitution of an individual  Phenotype -it is the final product or all the observable characteristics of an individual.  Depends on genotype and environmental factors . www.indiandentalacademy.com
  10. 10.  Trait - any detectable phenotypic property or character.  Linkage - two genes situated close together on same chromosome are said to be linked. www.indiandentalacademy.com
  11. 11.  Heritability-proportion of the phenotypic variance attributable to genotype.  Genome- contains the entire genetic content of chromosomes present within a cell or an organism. www.indiandentalacademy.com
  12. 12.  Multifactorial inheritance- if the genetic variation of a particular phenotypic trait is dependent on the simultaneous segregation of many genes & affected by environment. www.indiandentalacademy.com
  13. 13. Development of genetics  Mendelism - Gregor Johann Mendel.  He made his discoveries by analysis of results after crossing varieties of Garden pea (Pisum sativum) round or wrinkled seeds tall or dwarf plant yellow or white flowers He crossed varieties differing only in one pair of these characteristics www.indiandentalacademy.com
  14. 14. In his monohybrid experiments he found the genotypic ratio of 1 when he crossed pure varieties with opposing traits. R R r Rr Rr r Rr Rr www.indiandentalacademy.com
  15. 15. R r R RR Rr r Rr rr Crossing the second generation in which he obtained plants with only round seeds , he obtained genotypic Ratio of 1:2:1 www.indiandentalacademy.com
  16. 16. Dihybrid cross: When he crossed the second generation of plant variable in two characteristics he obtained a phenotypic ratio of 9:3:3:1 SY Sy sY sy SY SSYY SSYy SsYY SsYy Sy SSYy SSyy SsYy Ssyy sY SsYY SsYy ssYY ssYy sy SsYy Ssyy ssYy ssyy www.indiandentalacademy.com
  17. 17. Mendel’s laws:  First law-a unit of genetic information is transmissible unchanged from generation to generation.  Second law- alternate forms of the gene must segregateduring gamete formation and recombine independently in the offspring to provide ratio of 1:2:1. www.indiandentalacademy.com
  18. 18.  Third law or Law of Independent assortment – independent assortment occurs only when genes affecting different characters are on different chromosomes. In other words genes that are not alleles are distributed to gametes independently to each other. www.indiandentalacademy.com
  19. 19.  Law of Uniformity –when 2 homozygotes with different alleles are crossed all of the off springs of first generation are identical heterozygotes.  Law of Seggration –each individual possess 2 factors which determine specific characteristic, a parent transmits only 1 of these factors to any particular off spring.It is purely a matter of chance which of the 2 factors get transmitted. www.indiandentalacademy.com
  20. 20. Human chromosome  These are thread like structures located in the cell nucleus.  Each species has a specific number of chromosomes  Humans have 23 pairs or 46 .  22 pairs are autosomes ,1 pair is sex chromosomes XX/XY  Chromosomes vary in shape depending on the position of centromere www.indiandentalacademy.com
  21. 21. www.indiandentalacademy.com
  22. 22.  Individual chromosomes differ not only in position of centromere but also in their overall length(amount of DNA )  Human chromosomes are divided into 7 groups depending on size ,position of centromere, presence or absence of satellites  If the allele are identical it is called homozygous ,if the alleles differ it is called heterozygous www.indiandentalacademy.com
  23. 23. Centromere Middle Off center If close to the end At one terminal end tip Name Metacentric Sub metacentric Acrocentric(in this the short knob like on the short arm is called satellite Telocentric www.indiandentalacademy.com
  24. 24. Group chromosome description A 1-3 Largest ;1&3 mc,2sc B 4-5 Large ;sc C 6-12 &X Medium size;sc D 13-15 Medium size;ac with satellites E 16-18 Small ;16 mc,17&18 sc F 19-20 Small;sc G 21-22 &Y Small;ac www.indiandentalacademy.com
  25. 25. Modes of inheritance  Population genetics deals with the study of mode of inheritance of traits and distribution of genes in populations.  A trait is a particular aspect or characteristic of the phenotype.  A trait can be-  Monogenic  Polygenic/ multifactorial www.indiandentalacademy.com
  26. 26.  All human beings normally have 22 homologous pairs of chromosomes called autosomes that are numbered by size and other characteristics.  Also , one pair of sex chromosomes may be homologous (X, X) in females or only partly homologous (X, Y) in males.  Genes at the same locus on a pair of homologous chromosomes are alleles. www.indiandentalacademy.com
  27. 27.  When both 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. www.indiandentalacademy.com
  28. 28.  Exception to this- gametes contain only single representative of each pair of chromosomes.  When 2 gametes join at fertilization- new individual with paired genes, one from father & other from mother is formed. www.indiandentalacademy.com
  29. 29. Monogenic Traits  Traits that develop because of the influence of a single gene locus are monogenic.  Also called as mendelian traits.  Eg-blood group/hemophilia  Also called as-discrete or qualitative (yes or no)  If they are present, these traits still may be variable and quantifiable in some cases. www.indiandentalacademy.com
  30. 30. Autosomal dominant traits and penetrance  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 the same (homozygosity), then the effect is autosomal recessive. www.indiandentalacademy.com
  31. 31.  The trait (phenotype) is dominant or recessive and not the gene itself.  The nature of the traits is studied by constructing family trees called pedigrees in which males are denoted by squares and females by circles, noting who in the family has the trait and who does not. www.indiandentalacademy.com
  32. 32.  The study of multiple families will yield the following criteria for autosomal dominant inheritance: (1) The trait occurs in successive generations that is, it shows vertical inheritance (2) On the average, 50% of the offspring of each parent who has the trait also will have the trait www.indiandentalacademy.com
  33. 33. (3) if an individual has the gene that results in the trait, each child has a 50% chance of inheriting the gene that leads to the expression of the trait (4) males and females are equally likely to have the trait (5) parents who do not have the trait have offspring who do not have the trait. www.indiandentalacademy.com
  34. 34. www.indiandentalacademy.com
  35. 35.  Exceptions to this will be seen in-  Trait showing nonpenetrance in a particular offspring.  A new mutation occurred in the sperm or egg that formed the offspring.  Germinal mosaicism occurred, in which case one of the parents is mosaic in the germ cell line and the sperm or eggs are of two types-one cell line with and one cell line without the mutation. www.indiandentalacademy.com
  36. 36. Penetrance  When a person with a given genotype fails to demonstrate the trait characteristic for the genotype, the trait is said to show nonpenetrance in that individual .  Incomplete penetrance in any group of individuals who have the genotype. www.indiandentalacademy.com
  37. 37. Variable expressivity  In each individual the trait is present or not when discussing penetrance, if the trait is present, it may vary in its severity or expression.  Thus not all individuals with the trait may have it to the same extent and may express varying degrees of effect or severity. www.indiandentalacademy.com
  38. 38.  For example, osteogenesis imperfecta involving type I collagen  abnormalities. (1) multiple fractures (2) blue sclera (3) dentinogenesis imperfecta (4) hearing loss.  Variation occurs among the different clinical types of osteogenesis imperfecta www.indiandentalacademy.com
  39. 39. Autosomal recessive traits  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 the same (homozygosity), then the effect is autosomal recessive.  The concept of a gene carrier is used with autosomal recessive traits.  The carrier is heterozygous for a recessive gene that has only subtle, if any, expression of that single gene. www.indiandentalacademy.com
  40. 40.  Parents of a child with the autosomal recessive trait are typically heterozygous (carriers) and most often are diagnosed as normal. www.indiandentalacademy.com
  41. 41.  In autosomal recessive traits, the following three gene pairs are found:  AA-homozygous, not showing the trait or being a carrier for the trait.  Aa-heterozygous, not showing the trait but being a carrier of the trait  aa-homozygous, showing the trait. www.indiandentalacademy.com
  42. 42. www.indiandentalacademy.com
  43. 43. X-linked traits and Iyonization  Most of the genes on the X and Y chromosomes are not homologous and are unequally distributed to males and females.  Males are hemizygous for X-linked genes, meaning that they have only half (or one each) of the X-linked genes.  Because females have two X chromosomes, they may be homozygous or heterozygous for X-linked genes, just as with autosomal genes. www.indiandentalacademy.com
  44. 44.  A normally functioning homologous allele is not present on another chromosome, recessive genes on the one male X chromosome express themselves phenotypically as if they were dominant genes.  However, X-linked recessive genes must be present at the same (homologous) locus in females to express themselves fully. www.indiandentalacademy.com
  45. 45. www.indiandentalacademy.com
  46. 46.  Full expression of rare X-linked recessive phenotypes is almost completely restricted to males, and occasionally it is seen in females.  Variable expression in females is because of a process called LYONISATION. www.indiandentalacademy.com
  47. 47.  The lyonization process starts early in development when each cell in the female inactivates almost all of the genes on one of her two X chromosomes.  The homologous X chromosome in each succeeding cell also will inactivate the same X chromosomes of the pair. www.indiandentalacademy.com
  48. 48. Lyon hypothesis  In the female all or most of one X chromosome is genetically inactive and forms Barr body.  Decision whether maternally derived Xm or paternally derived Xp is inactive is made early in embryonic life and is random for each cell.  All cells subsequently have the same inactive X chromosome-Xm or Xp. www.indiandentalacademy.com
  49. 49.  There are phenotypes that "run in families" but do not adhere to patterns of mendelian inheritance.  These are referred to as complex or common diseases.  They have greater incidence compared with monogenic phenotypes.  These are the traits influenced by polygenic factors. Multifactorial inheritance- www.indiandentalacademy.com
  50. 50.  Multifactorial inheritance- trait is determined by the interaction of a number of genes at different loci, each with a small but additive effect, together with environmental factors.  Many congenital malformations are inherited as multifactorial traits & categorized as- continuous or discontinuous. www.indiandentalacademy.com
  51. 51.  multifactorial =polygenic + environmental  A change in phenotype depends on the result of the genetic and environmental factors present at a given time.  Thus compared with monogenic traits, polygenic traits are more amenable to change following environmental (treatment) modification. www.indiandentalacademy.com
  52. 52.  Examples of polygenic traits include height and intelligence quotient, both of which are continuous traits greatly influenced by genetic factors.  However, height and intelligence quotient also can be affected greatly by environmental factors, particularly if they are deleterious. www.indiandentalacademy.com
  53. 53. Discontinuous multifactorial traits  This describes the traits determined by multiple gene loci which are present or absent depending on the number or nature of the genetic and/or environmental factors acting.  When present these traits can vary continuously. www.indiandentalacademy.com
  54. 54.  The accepted explanation of discontinuous multifactorial variation rests on the assumption that there is an underlying scale of continuous variation of liability to develop the condition resulting from a combination of all the genetic and environmental influences involved. www.indiandentalacademy.com
  55. 55.  The condition is present only when the liability exceeds a critical threshold value,and the greater the level of liability beyond the threshold the more severe the disease www.indiandentalacademy.com
  56. 56.  Cleft lip and palate is a congenital malformation inherited as a multifactorial trait.  In the mildest form the lip alone is unilaterally cleft, whereas in the most severe form the lip is bilaterally cleft and the palatal cleft is complete. www.indiandentalacademy.com
  57. 57.  The parents of a cleft lip and palate patient are often unaffected, and there may be no family history of cleft lip and palate, but producing an affected child the parents are deemed to have some underactive genes for cleft lip and palate formation. www.indiandentalacademy.com
  58. 58.  The parents must have sufficient normally active genes to have normally formed lips and palates. Only when the balance exceeds certain threshold will the malformation occur, and the further the threshold is exceeded, the greater the extent of the malformation www.indiandentalacademy.com
  59. 59. www.indiandentalacademy.com
  60. 60.  Liability curve shifts to right for first degree relatives.  More severe the malformation- liability curve shifts to right.  5% of first degree relatives are affected if the clefting is bilateral ,whereas only 2% are affected if unilateral and incomplete. www.indiandentalacademy.com
  61. 61.  Some multifactorial traits show an unequal sex ratio.  Incidence is increased in the relatives of affected females.  This indicates that for this malformation the female threshold is higher than the male threshold. www.indiandentalacademy.com
  62. 62. Continuous multifactorial traits  Many normal human characteristics are determined as continuous multifactorial traits. These traits by definition have a continuously graded distribution.  The majority of individuals are centered around the mean. Such distribution is characteristic of a continuous multifactorial trait. www.indiandentalacademy.com
  63. 63.  For example - height. - malocclusion Not an abnormality or disease but a variation of occlusion in a continuous multifactorial trait. www.indiandentalacademy.com
  64. 64. Etiologic heterogeneity  Both continuous &discontinuous variation have a multifactorial basis so that different patients are not necessarily affected for same reason  Cleft palate patients no single cause can be identified ,it can be due to chromosomal disorder – Wolf Hirschhorn syndrome, trisomy 13 (patau syndrome),in monogenic disorders such as Vander Woude syndrome ,it may also be associated with cigarette smoking ,alcohol , drugs. www.indiandentalacademy.com
  65. 65. Twin studies  Twin studies are useful in study of population genetics.  To determine the role of genetic and environmental factors.(nature vs nurture)  Twins can be dizygotic or monozygotic www.indiandentalacademy.com
  66. 66.  Dizygotic /fraternal twins –they develop from two different embryos  Genetically alike like any other siblings  Can be of different sex  Resemblance only like siblings • Monozygotic /identical twins –they arise from a single fertilized ovum • Identical genetic makeup • Same sex • Resemble each other www.indiandentalacademy.com
  67. 67. Various methods have been used to differentiate  Hair&eye color  Ear form  Teeth morphology  Phenylthiocarbamide taste sensitivity  Blood groups  Serum proteins (gamma globulins)  Dermatoglyphics www.indiandentalacademy.com
  68. 68. Concordance & Discordance  Twins are concordant if they both show a discontinuous trait and discordant if only one shows the trait.  As twins usually share a similar family environment it may be difficult to separate the relative extent of environmental (nurture) and genetic contributions (nature) to a multifactorial trait www.indiandentalacademy.com
  69. 69.  Monozygotic twins have similar genotypes  Dizygotic twins are like siblings.  If a condition has no genetic component concordance would be expected to be similar for both types of twins. www.indiandentalacademy.com
  70. 70.  For a single-gene trait or a chromosomal disorder the monozygotic concordance rate will be 100%, whereas the dizygotic rate will be less than this and equal to the rate in siblings.  For discontinuous multifactorial traits with both genetic and environmental contributions, the rate in monozygotic twins, although less than 100%, will exceed the rate in dizygotic twins. www.indiandentalacademy.com
  71. 71.  In cleft studies, the monozygotic twin concordance rate for cleft lip and palate and cleft palate is 35 and 26 per cent, respectively. And for dizygotic twins 5 and 6 per cent, respectively. (Connor and Ferguson- Smith. 1993).  This reflects the heritability of the condition,higher the monozygotic concordance more the genetic contribution. www.indiandentalacademy.com
  72. 72. Twin studies for occlusal & dentofacial structures • Lundstorm (1948)-concluded that genetic factors have greater influence on craniofacial structures. • Lundstorm (1955)-genetic factors have greater influence on sagittal apical base relationship • Krause Wise&Frei (1959)-concluded that morphology of craniofacial bones are under strong genetic influence www.indiandentalacademy.com
  73. 73. • Krupanidhi &V.Surendra Shetty(1989)-assessed amount of genetic &environmental influence on dental measurements in twins  Statistically insignificant intrapair difference in MZ twins in 11 out of 13 parameters(PMBAW,PMD,basal arch width,tooth material,arch perimeter,intercanine width,overjet,overbite,curve of spee, III rugae position &midline)  Intermolar width & palatal depth showed significant difference.  significant difference in DZ twins for 5 parameters - premolar diameter, upper tooth material, intercanine width; lower intermolar width, overbite and curve of spee  may be due to different genetic material.www.indiandentalacademy.com
  74. 74.  Ferguson –Smith(1993) cleft study ,the monozygotic twin concordance rate for CLP& CP was 35 &26 % respectively dizygotic twins 5& 6 % respectively www.indiandentalacademy.com
  75. 75. Mutations A mutation is defined as an alteration or change in genetic material . Mutations are due to  Mutagenic factors –radiation,chemicals etc.  Spontaneous errors in DNA replication &repair. www.indiandentalacademy.com
  76. 76.  main groups of chemicals which,cause mutation are-  Base analogues which mimic standard bases, but pair improperly (e.g. 5-bromouracil)  Alkylating agents which add alkyl groups to bases and hamper correct pairing (e.g. nitrogen mustard or ethyl methane sulphonate)  Intercalating agents which intercalate with DNA and distort its structure (e.g. deamination by hydroxylamine). www.indiandentalacademy.com
  77. 77.  Mutations can be coded or noncoded .  Coded are the once that are transmitted.  Mutations of the somatic cells cannot be transmitted ,if it occurs in gamete cells it can be transmitted.  Mutations can be further divided into -  length mutations & point mutations. www.indiandentalacademy.com
  78. 78.  In a point mutation a single nucleotide base is replaced by a different nucleotide base.  transition –purine to purine pyrimidine to pyrimidine  transversion – purine to pyrimidine or vice versa www.indiandentalacademy.com
  79. 79.  Synonyms –mutations does not alter the polypeptide product of gene also called silent.  Non synonymous –mutations lead to alterations in the encoded polypeptide www.indiandentalacademy.com
  80. 80.  Missense –a simple base pair substitution can result in coding for a different amimoacid and synthesis of altered protein.  Nonsense –a substitution that leads to the generation of out of stop codon which will result in premature termination of translation of polypeptide chain. www.indiandentalacademy.com
  81. 81. Deletion/insertion  Deletion is the loss of 1 or more nucleotides  Insertion is the addition of 1 or more nucleotides  results in FRAME SHIFT mutation if these are not in a multiple of 3 www.indiandentalacademy.com
  82. 82.  The majority of mutations are likely to cause reduced fitness ,a reduced ability of the resulting zygote to contribute progeny to next generation ,in this way harmful genes tend be eliminated from the population  A balance between the production of disadvantageous alleles through mutation &their elimination by selection results in the presence of harmful alleles in the population at a low frequency www.indiandentalacademy.com
  83. 83. Chromosomal aberrations  Alterations of the genetic material which involves many genes & large amount of DNA 1. Numerical aberrations 2. Structural aberrations www.indiandentalacademy.com
  84. 84. 1. Numerical aberrations  Euploidy –triploidy,tetraploidy  Aneuploidy –monosomies,trisomies tetrasomies www.indiandentalacademy.com
  85. 85. Structural aberrations  Translocations –transfer of genetic material from one chromosome to another  Inversions –rearrangement within the same chromosome segment is rotated 180 degrees  Insertion –one segment is removed from normal position &inserted in different position  Deletion –a missing chromosomal segment  Ring chromosome  Isochromosome www.indiandentalacademy.com
  86. 86. www.indiandentalacademy.com
  87. 87. Chromosome abnormality  13 trisomy---Patau’s Mental retardation Microcephaly Cleft lip/palate Micrognathia,small eyes  18 trisomy--- Edward’s Mental retardation Brachycephaly Micrognathia Hypodontia CLP www.indiandentalacademy.com
  88. 88.  XO ---Turners Retarded growth Micrognathia Spade like chest Ovarian agenesis  21 trisomy --Down’s Brachycephaly Mental retardation Max hypoplasia Flat nasal bridge Delayed eruption Growth retardation macroglossia www.indiandentalacademy.com
  89. 89.  XXY--Klinefelter’s Gynecomastia Small testes Decreased facial hair  4p- Wolf-hirchhorn Mental retardation Abnormal facies CLP  5p- Cri –du-chat Mental retardation Microcephaly Characterstic cry www.indiandentalacademy.com
  90. 90. Role of neural crest cells  To understand genetic mechanisms involved in craniofacial morphogenesis at the molecular level in the embryo assists –  To know the role of genetics 1. The etiology of craniofacial abnormalities 2. Regulation of maxillary, mandibular, and tooth morphology. www.indiandentalacademy.com
  91. 91.  Facial development in the embryo is demarcated by the appearance of the pre-chordal plate (the cranial end of the embryo) on the fourteenth day of development.  Facial mesenchyme arises from neural crest cells.  These cells disrupt the ectodermal mesodermal junction and migrate into the underlying tissue as ectomesenchymal cells. www.indiandentalacademy.com
  92. 92.  During their migration they undergo a number of interactions with the extra-cellular matrix, and with adjacent epithelia to determine the ,nature and patterning of the neural, skeletal and connective tissue structures they will form.  Among the derivatives of the cephalic neural crest cells arc the maxilla, mandible, zygomatic, nasal bones, and bones of the cranial vault. www.indiandentalacademy.com
  93. 93.  Neural crest cell migration and the factors that cause these cells to localise in particular regions is not yet completely understood.  Their migration into the branchial arches occurs in a highly regulated manner.  This process is presumed to be under the control of genes known as homeobox genes which endow neural crest cells with a positional identity, which mediates aspects of craniofacial morphogenesis and patterning. www.indiandentalacademy.com
  94. 94. The role of cell adhesion molecules  cell adhesion molecules such as cadherins, integrins, immunoglobulins, and proteoglycans are glycoproteins on the external surface of the cell membranes, and are thought to be important in embryogenesis, particularly organ formation.  In craniofacial development the precise positioning of the neural crest cells in the branchial arches may involve changes in expression of cell adhesion molecules.  They are expressed and down regulated in neural crest cells during their migratory stages.www.indiandentalacademy.com
  95. 95. Homeobox genes  Homeobox genes are genes which are highly conserved through out evolution of diverse organisms and are now known to play a role in patterning the embryonic development .  These can be regarded as master genes of head & face controlling patterning, induction ,programmed cell death &epithelial mesenchymal interaction during development of the craniofacial complex . www.indiandentalacademy.com
  96. 96. Genes of particular interest in craniofacial developmemt are:  Hox group  Msx 1&Msx 2(muscle segment)  Dlx (distalless)  Otx (orthodontical)  Gsc (goosecoid)  Shh (sonic hedgehog) www.indiandentalacademy.com
  97. 97. Proteins encoded by these homeobox genes are transcription factors which control transcription of RNA from the DNA template within cell nucleus.  Transcription factors can switch genes on and off by activating or repressing gene expression, and therefore control other genes, producing a coordinated cascade of molecular events which ,in turn control patterning and morphogenesis. www.indiandentalacademy.com
  98. 98. At a cellular level this control is expressed through two main groups of regulatory proteins - growth factor family -steroid/thyroid/retinoic acid superfamily www.indiandentalacademy.com
  99. 99.  These regulatory molecules in the mesenchyme such as  fibroblast growth factor (FGF)  epidermal growth factor (EGF)  transforming growth factor alpha (TGFa)  transforming growth factor beta (TGFb)  bone morphogenetic proteins (BMPs)  are the vehicles through which homeobox gene information is expressed in the co-ordination of cell migration and subsequent cell interactions that regulate growth. www.indiandentalacademy.com
  100. 100.  By this means different parts of the DNA are activated in different cells regulating the different proteins ,enzymes .etc  These mechanisms hold a key to understand disease, dysmorphology & are subject of intensive research in craniofacial biology www.indiandentalacademy.com
  101. 101. Molecular genetics in oral and craniofacial dysmorphology  Mutations in fibroblast growth factor- affect suture development  Apert, Crouzon and Pfeiffer syndromes  Mutations in two transcription factors MSX2 and TWIST  Boston type craniosynostosis and Saethre- Chotzen syndrome www.indiandentalacademy.com
  102. 102.  mutation of core binding factor I gene: Cleidocranial dysplasia  mutation of long arm of chromosome 5 Treacher Collins syndrome www.indiandentalacademy.com
  103. 103. Molecular genetics in dental development  Role in epithelial and mesenchymal interaction  Bone morphogenetic proteins-2,4 & 7  FGF 1 & 8 via downstream factors MSX 1 and PAX 9 www.indiandentalacademy.com
  104. 104. Control of tooth development  Muscle specific homeobox genes Msx-l and Msx-2 are involved in epithelial and mesenchymal interactions.  Implicated in craniofacial development ie initiation,developmental position and further development of tooth buds  Msx 1 & Pax 9 have been implicated in non syndromic tooth agenesis  EDAI and NEMO syndromes that include tooth agenesis. www.indiandentalacademy.com
  105. 105. Disorders of tooth development  Amelogenesis imperfecta  It is a group of genetically heterogeneous disorders affecting enamel formation  Hypoplastic, Hypocalcified, &Hypomaturation forms have been described (Witkop 1988)  It exhibits autosomal dominant,autosomal recessive & X-linked inheritance  In humans two amelogens ,AMGX & AMGY have been cloned &mapped to X & Y chromosomes www.indiandentalacademy.com
  106. 106.  In 1997 MacDoughall et al mapped the ameloblastin gene within critical region for autosomal dominant AI at chromosome 4q21 .  Mutations of several genes may be involved in the etiology of various types of amelogenesis imperfecta. www.indiandentalacademy.com
  107. 107. Dentinogenesis imperfecta  It is autosomal dominant  Occurs in about 1:8000 live birth  Presents with brownish discoloration of teeth crowns ,susceptible to rapid attrition ,fragile roots & obliterated pulp chamber  One type of DI is coupled with osteogenesis imperfecta  Most patients with this type of DI have mutations & deletions for amino acid substitutions in genes for type 1 collagen www.indiandentalacademy.com
  108. 108. Hypodontia  Msx 1 is strongly expressed in dental mesenchyme throughout the bud ,cap &bell stages of odontogenesis  Vastardis et al (1996) demonstrated that a mutation in Msx 1 caused familial tooth agenesis & genetic linkage analysis of a family with autosomal dominant agenesis of 2nd premolar & 3rd molar identified a locus on chromosome 4p as the site of the Msx 1 gene www.indiandentalacademy.com
  109. 109.  Genetic factors are believed to play a major role in most of the cases of hypodontia with autosomal dominant, autosomal recessive, X-linked, and multifactorial inheritance reported.  A couple of genes (MSXl and PAX9) involved in dentition patterning have been found to be involved in some families with nonsyndromic autosomal dominant hypodontia although there are many other candidate genes, including KROX-26. www.indiandentalacademy.com
  110. 110. Peg shaped laterals  This can be an autosomal dominant trait with incomplete penetrance and variable expressivity as evidenced by the phenotype sometimes "skipping" generations and sometimes being a peg-shaped lateral instead of agenesis and sometimes involving one or the other or both sides.  A polygenic mode of inheritance also has been proposed. www.indiandentalacademy.com
  111. 111. Ectodermal dysplasia  Hypohidrotic ectodermal dysplasia is a heterogeneous disorder with clinically many distinct types  It is characterized by triad of – hypotrichosis hypohydrosis hypodontia  Hypodontia varies from few missing teeth to complete anodontia  Kere et al identified the gene for X-linked EDA & it was found to be expressed in keratinocytes, hair follicles and sweat glands. www.indiandentalacademy.com
  112. 112. solitary median maxillary central incisor syndrome  The presence of a single primary and permanent maxillary incisor which is in the midline and symmetric with normal crown and root shape and size, can be an isolated finding or can be part of the solitary median maxillary central incisor syndrome.  This heterogeneous condition may include other midline developmental abnormalities of the brain and other structures that can be due to mutation in the sonic hedgehog (SHH) gene, SIX3 gene. www.indiandentalacademy.com
  113. 113. Genetic influence on tooth number ,size,morphology,position,& eruption  Msx 1 &Msx 2 are responsible for stability in dental patterning .  Clinical evidence suggests that congenital absence of teeth &reduction in tooth size are associated  A study of children with missing teeth found up to half of their siblings or parents also had missing teeth . www.indiandentalacademy.com
  114. 114. Supernumerary teeth  Brook (1974) reported that prevalence of supernumerary teeth in British school children was 2.1%in permanent dentition with male:female ratio of 2:1 , in Hong Kong the prevalence was around 3 % & male :female ratio 6.5:1 , most common supernumerary tooth is the mesiodens ,these are commonly present in siblings & parents of the patients , it does not follow simple mendalian pattern www.indiandentalacademy.com
  115. 115. Abnormal tooth shape  Alvesalo &Portin (1969) provided substantial evidence supporting the view that missing ,malformed lateral incisors may be the result of common gene defect ,all of these defects show familial trends ,female preponderance,&association with other dental anomalies ,such as other missing teeth ,ectopic canines ,suggesting a polygenic etiology www.indiandentalacademy.com
  116. 116. Ectopic maxillary canines  Peck et al (1994) concluded that palatally ectopic canines were an inherited trait ,being one of the anomalies in a complex of genetically related dental disturbances –supernumerary teeth ,missing teeth , transposition ,tooth size reduction,other ectopically positioned teeth,it seems to be a polygenic trait.  Candidate genes that are proposed possibly to influence the occurrence of palatally displaced canines and hypodontia in developmental fields include MSXl and PAX9. www.indiandentalacademy.com
  117. 117. Submerged primary molars  It occurs most commonly in mandibular arch ,there is a high rate of concordance between the monozygotic twins ,number of studies provide evidence for genetically determined primary failure of eruption www.indiandentalacademy.com
  118. 118. Maxillary midline diastema  Numerous etiologies have been proposed –toothsize arch length discrepancy ,aberrant labial frenum attachment ,parafunctional habits, tooth loss , periodontal disease, deep bite ,maxillary midline pathology ,broadbent phenomenon ,Gardinger stated that parents &offsprings appear to share dental phenotype ,a few authors found heredity to play a greater role in MMD www.indiandentalacademy.com
  119. 119.  Class II div 1 malocclusion –study done by Harris (1975) show a higher correlation coefficient between patient & his immediate family than data from random pairings of unrelated siblings,thus supporting the concept of polygenic inheritance www.indiandentalacademy.com
  120. 120.  Class II div 2 malocclusion –it is a distinct clinical entity & is a more consistent collection of definable morphometric features occurring simultaneously i.e. a syndrome ,this often occurs in a combination with some dental features like poorly developed cingulum on upper incisors & characteristic crown root angulation ,teeth thinner in labio lingual dimension,a further feature is fowardly rotating mandibular development ,which contributes to deep bite ,chin prominence &reduced lower face height www.indiandentalacademy.com
  121. 121.  In study done on twins ,there was 100% concordance for class II div 2 among monozygotic twins &90 % dizygotic twins were discordant  Studies point to probably autosomal dominant with incomplete penetrance &variable expressivity www.indiandentalacademy.com
  122. 122.  Class III malocclusion-the most famous example of a genetic trait in humans passing through several generations is the pedigree of the so called – Hapsburg jaw ,this was famous mandibular prognathism demonstrated by several generations of Hungarian/Austrian monarchy www.indiandentalacademy.com
  123. 123.  Strohmayer (1937) did a detail pedigree analysis & found out that it was a autosomal dominant trait,other studies found out it to be polygenic trait  a variety of environmental factors are considered in its etiology,enlarged tonsils,nasal blockage,congenital anatomic defects,endocrine,posture,trauma/disease www.indiandentalacademy.com
  124. 124. ENVIRONMENTAL AND GENETIC INFLUENCES ON BILATERAL SYMMETRY  Three types of asymmetry:  Directional  Antisymmetry  Fluctuating asymmetry. www.indiandentalacademy.com
  125. 125.  Directional asymmetry occurs when development of one side is different from that of the other during normal development.  The human lung having three lobes on the right side and two lobes on the left side  This may be predicted before development occurs, it is under significant genetic influence. www.indiandentalacademy.com
  126. 126.  Antisymmetry occurs when one side is larger than the other, but which side is larger is variable in normal development and cannot be predicted before development  Antisymmetry is much less common than directional asymmetry.  These two types of asymmetry are considered developmentally normal.  Like directional asymmetry, antisymmetry has a significant genetic component that is not fully understood. www.indiandentalacademy.com
  127. 127.  The third type of asymmetry, fluctuating, occurs when a difference exists between right and left sides, with which side is larger being random.  This reflects the inability of the individual to develop identical, bilaterally homologous structures. www.indiandentalacademy.com
  128. 128.  Fluctuating asymmetry has been observed in the primary and permanent dentitions.  The greater amount of fluctuating asymmetry for the distance between cusps on each tooth than for the overall crown size of primary second molars and permanent first molars indicates that the occlusal morphology of these teeth is influenced more by environmental factors than the overall crown size. www.indiandentalacademy.com
  129. 129. GENETIC FACTORS AND EXTERNAL APICAL ROOT RESORPTION  The degree and severity of external apical root resorption associated with orthodontic treatment is multifactorial, involving host and environmental factors.  Genetic variation accounts for 50% to 64% of the variation in EARR of the maxillary incisors. www.indiandentalacademy.com
  130. 130.  Variation in the interleukin-lb gene (IL-l B) in orthodontically treated individuals accounts for 15% of the variation in EARR.  Persons in the orthodontically treated sample who were homozygous for IL-1B allele "1" were estimated to be 5.6 times more likely to experience EARR of 2 mm or more than those who were heterozygous or homozygous for allele "2“(Hartsfield and Everett AJO 2003) www.indiandentalacademy.com
  131. 131. Role of epigenetic factors  Etiology of malocclusion genetic environmental  More important is to understand the interaction.  The form & size of teeth is principally determined by genetic factors , but growth and final morphology of the dentofacial structures is also influenced by environmental factors. www.indiandentalacademy.com
  132. 132.  The influence of genetics on dentofacial morphology does not imply that genetic information is solely located in bones ,but also in neurological ,muscular & neuromuscular fields which have influence on skeleton. www.indiandentalacademy.com
  133. 133.  Mastication ,speech ,facial expression & swallowing are examples of neuromuscular patterns .  Although they are under conscious control ,there is no basis to suggest that these patterns can be changed permanently. www.indiandentalacademy.com
  134. 134.  Although the bones are also influenced by functional matrix, the functional matrix comprises of neuromuscular activity which is influenced by genetics as well as environmental factors .  This will have a direct bearing upon the extent to which a particular malocclusion can be influenced by therapeutic environmental intervention.  Salzman (1972) highlighted the familial nature of tongue thrusting,jaw posturing, & orofacial soft tissue mannerism . www.indiandentalacademy.com
  135. 135. Human genome project  Begun formally in 1990, the U.S. Human Genome Project is a 13-year effort coordinated by the U.S. Department of Energy and the National Institutes of Health. www.indiandentalacademy.com
  136. 136.  Determine the sequences of the 3 billion chemical base pairs that make up human DNA.  identify all the approximate 30,000 genes in human DNA.  Locate genes to specific chromosomes.  Identify near neighbours of genes.  store this information in databases.  Determination of gene defects.  Various linkage analysis. Project goals www.indiandentalacademy.com
  137. 137. The Oral &Craniofacial genome project seeks to set up collaborative laboratory research projects on human &mouse embryonic tissue The objective is to build up DNA libraries with a view to discover the genes for normal & abnormal oral & craniofacial development . www.indiandentalacademy.com
  138. 138. Conclusion  Contrary to the presumption that malocclusions of "genetic cause" are less amenable to treatment than those of an "environmental cause," a change in environmental factors can affect a polygenic trait with a high estimate of heritability.  The effect depends on the response of the patient to the change in environment (e.g., treatment). www.indiandentalacademy.com
  139. 139.  In the future, orthodontists ability to treat patients better will depend on investigations into how environmental factors affect gene expression that influences malocclusion. www.indiandentalacademy.com
  140. 140. We used to think that our fate is in stars Now we know that in large measure it is in our GENES. For more details please visit www.indiandentalacademy.com www.indiandentalacademy.com

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