Role of genetics in oral health / dental implant courses by Indian dental academy

☻INDIAN DENTAL ACADEMY
Leader in continuing Dental Education
www.indiandentalacademy.com
ROLE OF GENETICS
IN ORAL
HEALTH

Ancient philosophers have said that
MANMAN
is made upis made up
ofof
44 elements namelyelements namely
FIRE,WATER,EARTH AND AIRFIRE,WATER,EARTH AND AIR
And scientists say the same,And scientists say the same, MANMAN is made upis made up
ofof
44 elements namelyelements namely
Adenine, Guanine, Cytosine, ThymineAdenine, Guanine, Cytosine, Thymine

Dr.Vikrant Mohanty
CONTENTS
Introduction
Historical background
Basic consideration
Genetics in tooth development
Genetics in oro-facial disorders
Preventive measures for genetic disorders
Advances in genetics
Conclusion
Bibliography
☻Dr.Vikrant Mohanty
Dr.Vikrant Mohanty www.indiandentalacademy.com

KEY WORDS
Alleles: Genes responsible for contrasting characteristic
feature
Genome: All genes carried by a cell
Genotype: Genetic constitution of a person
Phenotype: Appearance of an individual that results
from interaction between genotype and environment
Autosomal and Sex–linked Inheritance: Disorder that
is determined by a gene on the autosome or a sex
chromosome
Autosomal Dominant: A gene on the non-sex
chromosomes which manifests in heterozygous
condition
Autosomal Recessive: A gene on the non-sex
chromosomes which manifests in homozygous conditionwww.indiandentalacademy.com

X or Y linked inheritance
Central Dogma: Concept that genetic information is
usually only transmitted from DNA to RNA
Codon: A sequence of three adjacent nucleotides which
codes for one amino acid
Multifactorial inheritance: Inheritance controlled by
many genes with small additive effects plus the effects of
the environment
Monozygotic twins: Type of twins derived from a single
fertilized ovum
Dizygotic twins: Type of twins produced by fertilization
of two ova by two sperms
Pedigree Analysis: Family tree in short handwww.indiandentalacademy.com

HISTORICAL BACKGROUND
 Leeuwenhoek [1632-1723] –
“SPONTANEOUS EVOLUTION”
 Linnaeus [1707-1778] –
“FIXITY OF SPECIES”
 Pasteur [1822-1895] – “Omne vivum e vivo”
 “PREFORMATIONISM” in the 17th
and 18th
century
Dr.Vikrant Mohanty

 Wolfe [1738-1794] – “EPIGENESIS”
 Charles Darwin – “Founder of the
modern evolutionary theory”
“PANGENESIS”
“USE AND DISUSE THEORY”
 Weisman “GERMPLASM Theory”
Dr.Vikrant Mohantywww.indiandentalacademy.com

 “GREGOR
MENDEL”
“FATHER
OF
GENENTICS”
“Pisum sativum”
– Self fertilizing
-- Easy to cultivate
-- Definite inherited
differences
Seeds Smooth Wrinkled
Yellow Green
Gray
coat
White
coat
Pods Full Constrict
e-d
Green Yellow
Stem Axial
pods &
flowers
Terminal
pods &
flowers
Long
length
Short
length

 Law of Segregation:
SS x ss
smooth wrinkled
SS Ss
Ss sss
S
sS
3 smooth and 1 wrinkled
Monozygotic

SSYY x ssyy
Smooth yellow Wrinkled green
SsYy Ssyy ssYy ssyy
Law of Independent assortment- Dizygotic

Law of Co-dominance:
– e.g. ABO blood group
SS X SS
SS
SS X SS
SS

Dr.Vikrant Mohanty
BASIC CONSIDERATIONS
 CELL Cytoplasm, Cellular organelles,
Nucleus
 Cellular organelles:
 ER + Ribosome – “SYNTHESIS HOUSE”
 Mitochondria – “POWER HOUSE”
 Peroxisomes + Lysozymes – “WASTE MANAGEMENT”
 Golgi complex – “PACKAGING HOUSE”
 Nucleus – “BRAINS”
Dr.Vikrant Mohanty

Dr.Vikrant Mohanty
NUCLEIC ACID
DNA
RNA
NUCLEOTIDES
Nitrogenous
base
Sugar Phosphate
Purines Pyrimidines
Cytosine Uracil Thymine
Adenine Guanine

Dr.Vikrant Mohanty
☻REPLICATION
☻TRANSCRIPTION
☻TRANSLATION
Dr.Vikrant Mohanty

Dr.Vikrant Mohanty
CHROMOSOMES
 “Colored Bodies” made up of supercoils of
DNA
 Parts of Chromosomes:
 Chromatids
 Centromeres
 Telomeres
 Chromatin
 Karyotype:
 Number, size and shape of the chromosome
of an individual

Dr.Vikrant Mohanty
 Karyogram:
 Photomicrograph of chromosomes arranged in
descending order of size
 Chromosomal Nomenclature:
 p-short arm
 q-long arm
 del-deletion
 t-translocation
 inv-inversion
 + or – gain or loss of a part of chromosome
 E.g.- 47,XY,+21 – Down’s syndrome
46,XY,t(2;4),(p2.3;q2.5)
Dr.Vikrant Mohanty

GENETICS IN
TOOTH DEVELOPMENT
 PATTERNING OF DENTITION:
FIELD THEORY-Butler
CLONAL THEORY-Osborne
 Various Genes:
Msx
Dlx
Barx-1
Bone morphogenic proteins
Fibroblast growth factor
Sonic hedgehog
Pax genes

 Msx Genes
Related to Drosophila muscle segment
homeobox genes
Msx 1 and 2 have been identified in relation to
Odontogenesis
Exhibit very high specific horse shoe shaped
fields of corresponding mesenchymal
expression of the 1st
arch
Msx 1 is localized in dental follicle and papilla
Msx 2 is localized in enamel organ

 Dlx Genes: Dlx 1 and 2
Bear homology with Distal-less gene of
Drosophila
Are expressed in the region of future
molars
 Barx-1:
Homeobox gene containing transcription
factor that express in ectomesenchyme of
the 1st
branchial arch
Along with Dlx 1 is expressed in posterior
region

 Bone morphogenic proteins:
Is a large family of dimeric proteins within the
Transforming growth factor beta superfamily
BMP 2,4 and 7 are expressed in
presumptive dental epithelium during early
tooth development
BMP 4 is the main signal molecule for
inducing the odontogenic potential in the
mesenchyme
 Paired Box Genes [PAX]:
PAX 9 is responsible in tooth morphogenesis

 Fibroblast Growth Factor [Fgf]:
Large family of heparin binding proteins
responsible to mediate growth and development
of wide region
Fgf 4,8,9 are most commonly expressed
Fgf 8 and 9 expressed in presumptive dental
epithelium during early tooth development

Fgf 4 and 8 are expressed in epithelial cell
of the developing tooth germ when the
epithelial and mesenchymal interactions
have began
Fgf 4 and 8 are up regulated in cap stage
in the primary and secondary enamel knot
regions

 Sonic Hedge hog [Shh]:
Encodes a signal peptide that mediates
both short and long range patterning in
signaling centers
Shh is expressed in epithelial thickening in
the horse shoe shaped lamina
Is strongly expressed in Enamel knots

CLASSIFICATION OF
GENETIC DISORDERS
♫ SINGLE GENE DISORDERS
♫ CHROMOSOMAL ABNORMALITIES
♫ MULTIFACTORIAL DISORDERS
♫ ACCQUIRED SOMATIC GENETIC DISORDERS

GENETICS IN ORO-FACIAL DISORDERS
 Amelogenesis Imperfecta:
Heterogeneous group of genetic disorders causing
hypoplastic and hypomineraliased enamel formation
Autosomal Dominant
Autosomal Recessive
X-linked inheritance
 Autosomal dominant defect is located on
Chromosome no.4q21
 X-linked inheritance defect is located on Xp21.1-
22.3

 Dentinogenesis Imperfecta:
 inherited defect of the dentine affecting both
the primary and secondary dentition and can
be associated to Osteogenesis Imperfecta
Types:
 DI Type I
 DI Type II or Hereditary opalescent dentine
 DI Type III Or “Brandy-wine type”
 All forms are Autosomal Dominantwww.indiandentalacademy.com

 DI Type I is located on Chromosome no.17
named COLIA 1 and Chromosome no.7
named as COLIA 2
 DI Type II is located on Chromosome
no.4q11-q21.1

CLEFT PALATE AND LIP
Both exhibit sex-linked or autosomal
inheritance with a multifactorial and polygenic
influence
 Cleft Lip [5-7th
week] and Cleft palate [7-
12week]
 Normal genetic evaluation is difficult and
most practical method is Pedigree
analysis.

 X-linked inheritance showed that Cleft
Palate was located on Xq21.3-q22
 Cell adhesion molecules like
Adhesin,Integrins,Syndecan,Cadherins
which are present on the outer surface of
cell membranes
 “SYNDECAN” [Elevation of the shelves]
and N-CADHERIN [fusion]

MALOCCLUSION:
Polygenic inheritance where the trait is determined
by interaction of no. of genes at different loci along
with additive effects of the environment
Role of Epigenetic factors:
Functional matrix by Moss
Soft tissue influence
Other factors like nutrition,climate,chronic illness,
starvation

 CRANIOFACIAL DYSOSTOSIS:
 Fibroblast growth factor is responsible for suture
development as they act through signal transduction
 CLEIDOCRANIAL DYSPLASIA:
Is a syndrome affecting bone and tooth development
by the mutations in RUNX2 gene
RUNX2 is a “MASTER GENE” for
 Development of bone
 Osteoblastic differentiation
Transition from bud to cap stagewww.indiandentalacademy.com

 ECTODERMAL DYSPLASIA:
 caused by actual mutation of “ECTODYSPLASIN”
 Regulates the function of enamel knot and hair placodes
 important signal regulating in tooth number and shape
 TREACHER-COLLIN SYNDROME:
 Is a autosomal dominant disorder and genetic analysis is difficult
due to reduced penetrance and high denovo mutation
 Defective gene located on chromosome no.TCOF1-3q32-33.1
 Candidate genes

 DOWN’S SYNDROME [TRISOMY 21]:
Non-disjunction of 21st
chromosome in maternal meiosis
I
Critical region identified is the distal end of the long arm
(21q2.2)
Robertsonian translocation
 Klinefelter’s syndrome {47,XXY}

 SICKLE CELL ANEMIA:
Substitution of valine at the 6th
position of the
beta globin chain instead of the 1st
position
Alteration of 2nd
base pair in the triplet coding
for glutamic acid i.e. GAG is changed into GTG
 THALESSAEMIAS:
Most common single group inherited disorder
in humans
Alpha- thalessaemias is located on ATRX-Xq13
Beta- thalessaemias can result due various
mutations like missense,mRNA splicing,chain
termination mutations.

PREVENTIVE AND SOCIAL
INTERVENTIONS
☻ Health promotional
measures:
☻ Eugenics
☻ Positive
☻ Negative
☻ Euthenics
☻ Other measures
☻ Consanguineous
marriages
☻ Late marriages
☻ Genetic counseling
☻ Specific protection
 Early diagnosis and
treatment:
– Detection of genetic
carriers
– Prenatal diagnosis
– Screening of newborn
infants
– Recognizing preclinical
cases
 Rehabilitation

☻Health promotional measures:
☻Eugenics:
☺Improving the genetic endowment of the
human population
☺Positive
☻Negative
☺Euthenics:
☺Environmental manipulation resulting in an
improved genotypewww.indiandentalacademy.com

☻Other genetic preventive measures
☻Consanguineous marriages
☻E.g. Albinism, Phenylketonuria,
Alkaptonuria
☻Late marriages
☻E.g. Down’s syndrome

Genetic counseling
☺ Genetic counseling
a two-way communication process which deals
with the human problems associated with the
occurrence or risk of occurrence of genetic
disorders in a family with the help of trained
professionals.
- American society of Human Genetics
☺ Genetic testing
☺ Genetic screeningwww.indiandentalacademy.com

TYPES OF GENETIC COUNSELING:
☺Prospective counseling
☺Retrospective counseling

Personal or family history suggestive
of genetic disorders
High risk ethnic groups i.e. known
carriers of genetic mutations
Ultrasound or prenatal testing suggest
a genetic disorder

☺Functions of Counselor:
☺Gather & document detailed family history
☺Educate pt.general genetic principles related
to disease risk
☺Assess & enhance the pt’s ability to cope
with the genetic information provided.
☺Relate non-genetic factors to expression of
the disease

☺Assist in determining the role of genetic
testing for the individual & family
☺Ensure that the pt. is aware of risks,
benefits & limitations of various genetic
testing options
☺Refer for additional medical support
services if necessary
☺Address medical management issues.www.indiandentalacademy.com

Assess risk based on personal & family
history &
discuss the availability &goals of genetic
counseling
If “at-risk” individual expresses interest
in counseling refer to multidisciplinary clinic
-Explain goals & services of evaluation
-Assess emotional ability to cope with stress
-Assess relevant medical history
-Pedigree collection & interpretation
Algorithm for Genetic counseling

☻Risk assessment confirmed with pedigree &
☻ Medical history
☻ Discussion of risk with patient
☻ Counseling regarding potential risk management
strategies
Discussions of availiabilty,risks,benefits
& limitations of DNA testing

Option of DNA testing declined
or not available
DNA testing requested
Consider option of
DNA banking
Return to primary care clinician
for follow up care based on
risk assessment
Pretest counseling &
Informed concern
Sample obtained & sent
Result disclosure &
reassessment of risks
& management
Return to primary care
clinician for follow-up
based on risk assessment

☺ Specific protection:
☺Protection from mutagens like X-rays and
ioniasing radiations
☻Early diagnosis and treatment:
☻Detection of genetic carriers
☻Prenatal diagnosis:
☻Amniocentesis-
☻Maternal age >35yrs
☻Pt’s with past history of down’s syndrome
☻Parents with known chromosomal
translocationwww.indiandentalacademy.com

☻Parents with child with metabolic disorders
☻Determination of sex when warranted in sex
linked diseases
☻Screening of newborn infants
☻Recognizing preclinical cases

POPULATION SCREENING AND
COMMUNITY GENETICS
◘ Community genetics:
¤ Branch of medical genetics which is concerned
with screening and prevention of genetic
diseases on a population basis.
◘ Population screening:
¤ Involves genetic testing on a equitable basis to all
relevant individuals in a defined population.www.indiandentalacademy.com

◘ Objectives:
¤ Enhance autonomy by enabling the
individual better informed about genetic
risks and reproductive options.
¤ Prevention of morbidity due to genetic
disease and eliminate the suffering caused
by it.

◘ Criteria for the screening programme:
◘ Disease
◘ Test
◘ Programme
◘ Various levels of applications:
◘ Primary prevention
◘ Antenatal
◘ Neonatal

Type of service Conditions Preventive or
screening actions
Primary prevention Rhesus hemolytic
disease
Congenital
malformation & rubella
−Post-partum use of
Anti-D globulin
−Immuniasation of girls
−Addition of folic acid in
maternal diet
−Avoidance of
mutagens & teratogens
eg.alcohol
Antenatal screening Congenital
malformations
Chromosomal
abnormalities
Ultrasound, maternal
alpha fetoprotein
Maternal age, serum
factors, family history

Type of service Conditions Preventive or
screening actions
Neonatal
screening
Congenital
malformations
Phenylketonuria
Sickle cell
anemia
Examination of
the new born for
early treatment
Biochemical
tests for early
treatment

 Advantages:
Informed choice
Improved understanding
Early treatment when available
Reduction in birth of affected
homozygotes

 Disadvantages:
Pressure to participate causing mistrust
and suspicion
Stigmatization and inappropriate
anxiety of carriers
Inappropriate reassurance if test isn't
100% sensitive.

Genetic registers
 Permits investigations and ensures
that families are not abandoned
from support
 Primary purpose is to maintain a two way conversation
between a genetic unit and relevant family members

 To maintain an informal two way
communication process between the family
and genetic unit.
 To offer carrier detection to relevant family
members as they reach adult life.
 To coordinate presymptomatic and prenatal
diagnosis when requested.
Functions of genetic registers

 To coordinate multidisciplinary management
of patient’s with complex hereditary
conditions such as the familial cancer
syndromes.
 To ensure effective implementation of new
technology and treatment.
 To provide a long term source information
and support www.indiandentalacademy.com

Disorders suitable for Genetic
registers:
– Autosomal dominant:
• Retinoblastoma
• Neurofibromatosis
– Autosomal recessive:
• Cystic fibrosis
• Sickle cell anemia
• Thalessemia
– X-linked disease:
• Hemophilia
– Chromosomal disorders:
• Deletions
• inversions

Dr.Vikrant Mohanty
RECENT ADVANCES IN
GENETICS
 Gene therapy
 Human Genome Project and Gene mapping
 DNA Technology

Dr.Vikrant Mohanty
Human Genome Project
and Gene mapping
 1969-Victor
Mckurick-human
genome concept
 Workshop at
Alta, Utah under
US Dept.of
Energy [DOE] in
1984 www.indiandentalacademy.com

Dr.Vikrant Mohanty
US congress in 1990
approved a 15yr Human
genome project, estimated
budget of 2,00,000,000
dollars per annum
Human Genome
Organiasation [HUGO]
coordinates various National
Genome Projects and has
centers in
Bethesda,USA,London,
Tokyo

Dr.Vikrant Mohanty
Project goals were to
 Identify all the
approximately 30,000
genes in human DNA
 Development of
physical maps
 Determine the
sequences of the 3 billion
chemical base pairs that
make up human DNA
 Store this information in
databases

Dr.Vikrant Mohanty
 Improve tools for
data analysis
 Transfer related
technologies to the
private sector
 Address the ethical,
legal, and social
issues (ELSI) that
may arise from the
project.

Dr.Vikrant Mohanty
 Genetic Map:
 Describes the order of
genes and defines the
position of gene
relative to other loci on
the same
chromosome.
 Distance of genetic
map are expressed in
recombination units of
Centimorgans [cM]
 Physical Map:
 Indicates the position
of a locus or a gene in
absolute values.

Dr.Vikrant Mohanty
 Expenditure - >3
billion dollars
 Manipulation
 Improving the
understanding &
development of
new strategies for
prevention &
treatment of
inherited diseases
PROS & CONS

GENE THERAPY
 Replacement of deficient gene product or
correction of abnormal gene to prevent a
pathological process
 Forms of gene therapy:
Germ-line
Somatic cell
 Uses:
Providing chemo-protection to normal cells
Providing DNA based Immuniasation
Killer cancer cells
Preventing coronary artery re-stenosis
Impairing viral replication

 Requirements of gene therapy:
Gene characterization
Target cell/Tissue/Organ
Vector system
 Based on vector system modes of gene
therapy:
Viral vectors- e.g. Retrovirus, Adenovirus
Non-viral vectors

Viral vectors:
Retrovirus: e.g. Murin leukemia
virus,Lentivirus
 Disadvantages:
Compliment mediated vector particle
inactivation
Introduction of small segments of DNA
Vectors require cell division for
transduction to enter the nucleus
Unstable & cannot be purifiedwww.indiandentalacademy.com

 Adenovirus
 Advantages:
Stable
Easily purified
Carries large base pairs of DNA up to 36Kb
Avoids insertional mutagenesis
 Disadvantages:
Transient action
Malignancy induction

 Non-viral vectors:
Complexes of DNA with lipids,
carbohydrates or other synthetic
chemicals
 Advantages:
Eliminate risk of viral contamination
Produced under controlled conditions

Disadvantage:
Low gene transfer rate
Other methods of gene therapy:
Naked DNA injection
Liposome – large amounts transfer
but transient
Oligonucleotides
Stem cell transplantation
Animal models

 Various diseases where used:
Hemophilia
Cystic fibrosis
Thalessemia
Lung,Renal,Ovarian cancer
Phenylketonuria

DNA technology
Divided into :
Methods of DNA Analysis
DNA cloning
 DNA Analysis Methods:
Nucleic acid probes
Nucleic acid hybridization
Southern Blotting
Northern Blotting

 DNA cloning:
Is the selective amplification of a specific
DNA fragment to produce large amounts of
a homogenous DNA material
Methods:
In-vivo DNA replication
In-vitro polymerase chain reaction
DNA technology

Steps in DNA CLONING [in-vivo]
Generation of DNA fragment
Recombination of DNA fragments
Vectors
Transformation of the host organism
Screening of recombinant vectors

 APPLICATIONS:
Gene structure/functions/Mapping
Clinical Genetics
Prenatal diagnosis
Presymptomatic diagnosis
Carrier detection
Population Genetics
Diagnosis and pathogenesis of diseases
Genetic
Acquired
 Gene Therapy
Biosynthesis e.g. Insulin,Interferons
Agriculture

Dr.Vikrant Mohanty

Dr.Vikrant Mohanty
GENES FORETELL YOUR FUTURE
“Nanogeneseq” – gene sequencing and
reading system that can foretell your
future by decoding your gene
Uses Nanotechnology and fractal
geometry
Advantages:
Efficient than DNA polymerase chain
reaction method
Consumes less power
Overcomes DNA overlapping problemswww.indiandentalacademy.com

Dr.Vikrant Mohanty
Applications:
Various diseases
Pharmaceutical applications
DNA separations
Developed by Dr.V.S Ajit Kumar and
Dr.V.S Arun Kumar in Trivandrum
* The Week

Dr.Vikrant Mohanty
CONCLUSION
“The quest for knowledge is
endless but to equip
ourselves with what is
present will not only help us
better understand but also
enable us to carry on the
quest for that endless
knowledge”

Dr.Vikrant Mohanty
BIBILOGRAPH
Y
 Emery‘s Elements of Medical Genetics – Robert
F.Muellar 11th
edition
 Genetics – Manroe W.Strickberger,3rd
edition
 Genetics -The Dental Clinics of North America,Jan,1975
 Clinical Oral science –Malcolm Harris
 Principles of Internal Medicine – Harrison,15th
edition,Vol.1

Dr.Vikrant Mohanty
 Preventive and social Medicine – K.Park,17th
edition
 Developmental biology and building of a tooth – Irma
Thesleff,Quintessence Int.Vol.3,No.5,2003.
 The genetic control of early Odontogenesis –
Martyn.T.Cobourne,Brit.Journ.of
Orthodontics,Vol.26,1999,21-28.
 The heritability of Malocclusion: Influence of Genetics in
Malocclusion, Part 1&2 – Mossey, Brit.Journ.of
Orthodontics,Vol.26,1999,195-208
BIBILOGRAPHY

Dr.Vikrant Mohanty
Thank you

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