This document discusses genetics and periodontics. It provides an introduction to genetics concepts like genes, genomes, alleles and genetic testing. It discusses the human genome project and evidence that genetics plays a role in periodontal diseases. Certain genes like IL-1, TNF-α and PGE2 are candidates for influencing periodontal diseases based on their roles in immune-inflammatory processes and bone metabolism. Genetic variations involved in periodontal diseases can be determined through studies of candidate genes, genomic scans and proteomics.

1. GENETICS IN
PERIODONTICS
GUIDED BY PRESENTED BY
DR.P.SURESH, MDS CH.SUMA PRIYANKA
PROF & HOD 1 st YEAR PG
DEPT.OF PERIODONTICS DEPT.OF PERIODONTICS
GDC&H, KADAPA

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CONTENTS
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 INTRODUCTION
 TERMINOLOGIES
 HUMAN GENOME PROJECT
 GENETICS & PERIODONTICS
 LEADING PERIODONTAL CONCEPTS
 EVIDENCE FOR THE ROLE OF GENETICS IN PERIODONTICS
 GENETIC TESTING
 GENES IN PERIODONTAL DISEASES

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 GENETIC STUDY DESIGNS
 HERITABILITY
PERIODONTITIS IN GENETIC SYNDROMES & OTHER DISEASES
GENE LIBRARY
 GENE THERAPY
 CONCLUSION
 BIBLIOGRAPHY

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INTRODUCTION
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Genetics is a branch of Biology concerned with the study of genes, genetic
variations and heredity in living organisms.
 “Gregor Johann Mendel” – “Father of Genetics”
 Trait inheritance
 Gene

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• In humans, the genes are located on 23 pairs of “Chromosomes”.
• “GENOME”.

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• 3 billion DNA base pairs (NHGRI).
• Codon.

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TERMINOLOGIES
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GENE: The segment of the genome that carries the instructions for a specific protein is the
“Gene” for that protein.
GENOME: term used to refer all the genes carried by an individual or a cell.
GENOTYPE: genetic makeup of an organism or cell.
GENETIC CODE: the consecutive nucleotide triplets that specify the sequence of aminoacids
for protein synthesis.
ALLELE: Alternative forms of a given gene differing in DNA sequence.
LOCUS: the physical location of a gene occupies within a chromosome or portion of genomic
DNA.
LINKAGE: the tendency for certain genes to be inherited together due to their presence on
the same chromosome.

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• POLYMORPHISM: When a mutation increases to a level involving >1% of the population, it is
referred to as polymorphism.
• SINGLE NUCLEOTIDE POLYMORPHISM: Polymorphism in individual bases.
-most common but minute.
-occur in a frequency of 1 in 1000.

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HUMAN GENOME PROJECT
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GOALS:
• Identify all the approximate 30,000 genes in human DNA.
• Determine the sequences of the 3 billion chemical base pairs that make
up human DNA.
• Store this information in databases.
• Improve tools for data analysis.
• Transfer related technologies to the private sector, and
• Address the ethical, legal, and social issues (ELSI) that may arise from the project.

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Milestones:
• 1990: Project initiated as joint effort of U.S. Department of Energy and the National
Institutes of Health.
• June 2000: Completion of a working draft of the entire human genome (covers >90% of the
genome)
• February 2001: Analyses of the working draft are published.
• April 2003: HGP sequencing is completed and Project is declared finished two years ahead
of schedule.

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CONCLUSIONS:
• The human genome is nearly the same (99.9%) in all people.
• Only about 2% of the human genome contains genes, which are the instructions for
making proteins.
• Humans have an estimated 30,000 genes; the functions of more than half of them
are unknown.
• Almost half of all human proteins share similarities with other organisms.
• About 75% of the human genome is “junk”.

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FUTURE CHALLENGES:
• Gene number, exact locations, and functions
• Gene regulation
• DNA sequence organization
• Chromosomal structure and organization
• Noncoding DNA types, amount, distribution, information content, and functions
• Coordination of gene expression, protein synthesis, and post-translational events
• Correlation of SNPs with health and disease
• Genes involved in complex traits and multi-gene diseases
• Developmental genetics, genomics

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DOES EVERYONE HAVE THE SAME GENES???
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• Differences among individuals are both genetically and environmentally determined.
• Differences due to genetics arise primarily because the same gene may differ in DNA
sequence between two individuals.
• These differences are termed as “Alleles”.

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GENETICS & PERIODONTITIS
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• Some data suggests that Smoking, DM, and Genetic influences put certain individuals at a
high risk for severe periodontitis.
• Management of the disease.
• “Everyone who does not maintain proper oral hygiene gets periodontal disease, but not
everyone gets the same severity of the disease”.

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LEADING PERIODONTAL CONCEPTS
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1965-1995:
i. Populations with poor plaque control and limited professional dental care have
widespread severe periodontitis.
ii. Individuals with poor plaque control for many years have severe generalized periodontitis.
iii. The severity of the disease depends on the combination of the bacterial challenge and the
length of time of exposure to the bacteria.

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Today:
i. Periodontitis require specific bacteria for the initiation and progression of attachment loss
and bone loss.
ii. There is “normal” host response to this bacterial challenge.
iii. Although the normal host response is primarily protective, it also causes tissue
destruction.
iv. Healing and repair are constantly going on in the periodontal tissues.

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V. In the majority of individuals with a moderate bacterial challenge, protection and repair
dominate destruction, and very little disease is clinically evident.
Vi. Some patients have “altered” host responses and develop more severe destruction.
Vii. Altered host responses may result from-
a) heavy bacterial challenges overwhelming the protective and repair
mechanisms.
b) the presence of disease modifiers that reduce the protective component of
the host response or amplify the destructive component.

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MODIFYING FACTORS:
• The factors that determine the severity and response to treatment are often called “Disease
modifiers”.
• Will change the trajectory of the clinical disease expression over time.
• So, an individual with a disease modifier is at increased risk for more severe signs and
symptoms at any given time in the disease, as compared with an individual without that
modifier.
• Eg; Smoking & Periodontitis.

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EVIDENCE FOR THE ROLE OF GENETICS IN
PERIODONTITIS
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In a study of 222 healthy children aged 0-18 years from Ohio, USA, pathogenic
strains of A.actonimycetemcomitans and P.gingivalis were detected in 48% and 36% of
children respectively, and both the species were detected in infants as young as 20 days old
(Lamell et al.2000).
Interestingly in a large group of subjects with gingivitis or minor periodontitis, A.a
and P.gingivalis were similarly prevalent 38% and 32% respectively. (Wolff et al.1993).
This shows that not only bacteria, but the host factors are also required for
periodontitis and this may lead to the development of the hypothesis that periodontitis may
have a genetic background.

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Lindhe & co-workers, in an experimental periodontitis study in dogs, noted that
with long-term plaque accumulation and gingivitis development, some of the dogs developed
only minimal loss of attachment or none at all.
In a population in Srilanka without access to dental care and absence of oral
hygiene, “Loe et al. (1986) were able to identify 3 sub-populations:
a) a group with no progression (11%)
b) a group with moderate progression (81%)
c) a group with rapid progression of (8%) periodontal breakdown.

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In a more recent study, the initiation and progression of periodontal breakdown
was studied in a remote village in West Java that was deprived of regular dental care (Vander
velden et al .2006). They found that 20% of the subjects developed severe periodontal
breakdown, whereas the remaining developed mild-moderate breakdown, suggesting that not
everyone is equally susceptible to periodontitis.

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SINGLE-GENE DISORDER MULTI-FACTORIAL DISEASES
1. Genetic factor Complex interaction among multiple genes and
environmental factors.
2. Evident in childhood. Adulthood, and an initiating factor must be present.
3. Tay-sachs disease, familial hypercholesteremia,
Down’s syndrome etc;
Heart diseases, hypertension, periodontitis etc;

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GENETIC TESTING
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• Any cellular material including a blood sample or a scraping of cells from the inside of the
cheek, may be examined.
• 3 types-
i. Testing for chromosomal abnormalities such as “Trisomy 21”.
ii. Testing for unusual mutations, such as BRCA1 as a risk factor for Breast cancer.
iii. Testing for common polymorphisms, such as those being studied for risk of severe
periodontal disease.

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WHICH GENES ARE IMPORTANT FOR PERIODONTAL
DISEASES??
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i. IL-1
ii. PGE2
iii. Matrix Metallo-proteinases (MMP’s).

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• There are many reports associating IL-1 levels in tissues and GCF with bone loss in more
advanced or severe periodontitis.
• Recent studies comparing the severity of bone loss with IL-1 levels in GCF showed essentially
a Straight-line relationship i.e; “the higher the levels of IL-1 in crevicular fluid, the more
severe is the bone loss”.
• Other studies showed that specific blocking of IL-1 & TNF-α in the gingival tissues, without
any plaque control measures, blocked a substantial part of the bone loss in a monkey model
of periodontal disease.

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• The extensive research of the past 20 years considers the following as candidates for genetic
influences on periodontal disease differences among individuals:
i) IL-1
ii) TNF-α
iii) PGE2
iv) Cytokines that regulate immuno-inflammatory processes- IL-10, IL-4, IL-13, IL-12.
v) Growth factors involved in wound healing and CT and bone metabolism.

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DETERMINING GENETIC VARIATIONS INVOLVED IN
PERIODONTAL DISEASES
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i. Use of Candidate genes
ii. Genomic scan
iii. Proteomics

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CANDIDATE GENES: Genes which are known to influence some key aspect of the biology
involved in the disease.
• Candidate genes in SNP’s are studied for association with disease.
GENOMIC SCAN: Starts with specific variations in the nucleotide sequence that are located
along the entire genome.
• The markers that are found to be associated with the disease define the physical locations in
the genome that are more likely than others to influence that disease.
• Each physical location that is identified on the genomic scan must then be explored for
potential genes of importance.
PROTEOMICS: involves the analysis of those genes that are more activated during the disease.

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GENETIC STUDY DESIGNS
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Once the genetic basis for a disease has been established, it is equally important
to determine-
i. Which alleles have measurable effect on phenotype
ii. Whether the prevention, diagnosis, or treatment of the disease can be improved, once
disease alleles are identified.

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i) Segregation analysis
ii) Twin studies
iii) Linkage and Association studies

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SEGREGATION ANALYSIS:
Inherited diseases “run” in families. The pattern of inheritance through
generations depends on-
i) Autosomes / Allosomes
ii) Dominant / Recessive
iii) Fully or Partially Penetrant
• A method of formal genetic analysis employed to determine whether or not a phenotype is
inherited.
• This method also allows the mode of inheritance to be determined i.e; AD/AR.

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• “Penetrance” refers to the probability that a particular phenotype will result from a
genotype.
• “Partially penetrant” means that only a fraction of individuals who inherit the disease alleles
will be affected.
• Generally segregation analysis cannot distinguish between genetic effects and measured
environmental causes of disease.

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TWIN STUDIES:
• The relative influence of genetic and environmental factors on complex diseases can be
estimated using twin studies.
• These studies are based on the fact that dizygotic twins share on average 50% of the genes
by descent, while the genes in monozygotic twins are identical.
• Thus, if heredity plays a significant role in periodontitis, the probability of having the same
disease in monozygotic twins will be much higher than in dizygotic twins.

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LINKAGE AND ASSOCIAION STUDIES:
• Used to map disease alleles to specific regions on chromosomes.
• Uses sets of families or pedigrees containing multiple affected individuals.
• Parameters- a) Mode of inheritance
b) Frequency of the marker allele in the population
c) Disease penetrance.
• Linkage can be detected if the marker and disease alleles are within 20-30 centimorgans
(CM) of one another.

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HERITABILITY
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• It measures the proportion of phenotypic variation that can be attributed to genetic
variation.
• Heritability is also always specific to a particular population in particular surroundings.

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HERITABILITY OF AGGRESSIVE PERIODONTITIS:
• Numerous studies have reported familial aggregation for aggressive periodontitis.
Spektor MD in 1985 has shown that both forms of AP (LAP & GAP) has genetic
mode of inheritance within the families.
• Marazita et al. in 1994 had evaluated more than 100 US families, which included 527 cases
and healthy subjects with aggressive periodontitis and found the data to be more consistent
with an “Autosomal Dominant” transmission.
• Saxen et al. in 1980 showed an AR mode of inheritance of AP among Finnish populations.

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• Schenkein et al. in 1994 proposed model of inheritance of LAP & GAP in families. He studied
that AP and IgG2 responsiveness to bacterial LPS are inherited independently as Dominant
traits within families.
• Segregation analysis with human families are hampered by various methodological factors,
which often are the lack of adequate statistical power due to small number of families, too
small or incomplete families, and a high heterogeneity between families.

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TWIN STUDIES:
Ciancio et al. in 1969 addressed the concordance of the periodontal condition in
twins, but the study design and low sample (7 MZ & 19 DZ twin pairs of age 12-17 yrs) didn’t
allow a clear conclusion on the concordance rate of early-onset periodontitis.

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LINKAGE & ASSOCIATION ANALYSIS:
• This method determines the chromosomal location of a gene that affects the specific
observable traits in the disease.
• For a gene that influences the disease to be identified by this technique, it must have a
“Substantial effect” on the disease, and its effects must be independent of other genetic and
environmental factors.
“Boughman et al; in 1986 reported genetic linkage for LAP in an extended family
from the Brandywine population in Eastern Maryland. They localized a major gene for LAP to
the vicinity of Vit.D binding protein on chromosome 4q.
• Recently, AP has been linked in 4 families with LAP marker located on chromospme1. ( Li Y in
2004).

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• More recently, a powerful linkage analysis technique called “Transmission disequilibrium
testing” was used with AP cases and found a significant role for polymorphisms in IL-1 genes
on chromosome 2q.
• Polymorphisms in the genes for IL-1 & IL-1β were significantly associated with AP, with the
strongest effect for IL-1β.

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ANTIBODY GENETICS (IgG2 & Fcγ receptors):
• IgG1, IgG2, IgG3.
• Serum IgG2 levels in LAP are higher than in GAP cases, and age-matched controls with no
disease, a finding that supports the concept that robust serum antibody response is
associated with protection in AP.
• Polymorphonuclear leucocytes.
• Antibody is critical to the efficiency of removing bacteria by specific binding to the bacterial
cell and binding to the surface receptors on PMN’s.
• The antibody, therefore amplifies the effectiveness of PMN’s by targeting specific bacteria.

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• Segregation analysis studies of IgG2 levels for members of 123 families with AP supports the
association between antibody levels and disease and strongly support a role for both genetic
control of IgG2 and antibody genetics in AP.
• The surface receptor that allows the PMN to bind the IgG antibody and then phagocytize the
bacterial cell is called “Fcγ receptor”.
• Polymorphisms in Fc receptors expressed on the surface of phagocytic cells recently have
been shown to be important determinants of susceptibility to infection.
• Ig FcγRII genes are found on chromosome 1, and FcγRII a polymorphism has 2 variations,
R131 & H131.

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Wilson & co-workers have shown that in patients with LAP, serum containing IgG2
antibodies is effective in phagocytizing A.a when employed in conjunction with neutrophils
that express Fcγ receptors capable of recognizing this antibody.

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HERITABILITY OF CHRONIC PERIODONTITIS:
• Genetics has only recently emerged as a major consideration in chronic periodontitis.
i. Although bacterial plaque is essential for the initiation and progression of periodontitis,
the amount of plaque is not a good predictor of the severity of destruction.
ii. Studies of identical twins who were separated at birth and raised in different families
showed that they develop similar levels of periodontitis as adults.

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• One of the studies included 110 pairs of adult twins (~40.3 yrs) , (63 MZ & 33 DZ pairs)
reared together and 14 MZ twins reared apart.
• Periodontal parameters- i) PPD
ii) CAL
iii) Plaque
iv) Gingivitis, and it was estimated that 38%-82% of the variance in
these measures could be attributed to genetic factors. (Michalowicz et al;1991).

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Michalowicz et al; in 2000 in a population-based twin study on 117 twin pairs,
assessed the heritability of the genetic and environmental variation in chronic periodontitis
and gingivitis. It showed that the investigated MZ twins (64 pairs) were more similar than DZ
twins ( 53 pairs) for CAL, the severity and the extent of the disease.
• The heritability was estimated to be ~50%, which was unaltered for smoking, oral hygiene,
age and gender.
• This study also showed no evidence of heritability of gingivitis.

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CANDIDATE GENES IN CHRONIC PERIODONTITIS:
i. IL-1 genotype
ii. Fcγ receptors in PMN’s
iii. HLA-DR antigens
iv. TNF
v. Vit.D receptor

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Patients who are IL-1 genotype positive
-have an increased inflammatory response in the presence of bacteria.
-have increased bacterial counts and more pathogens associated with active
periodontal disease.
-are at increased risk for severe periodontal disease.
- are less likely to respond favorably to periodontal therapy.

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• Findings from a systematic review of “Genetic factors and Periodontitis
development” by Silva MK et al, in 2017 concluded that among 25 polymorphisms in
7 interleukins (IL-1A, IL-1B, IL-4, IL-6, IL-8, IL-10, and IL-18)
3 cellular receptors (Fcγ receptors: FCGR2A, FCGR3A, and FCGR3B), and
5inflammatory mediators (COX-2, MMP-2, MMP-3, MMP-8, and MMP-9),
Polymorphisms in the IL-1A, IL-1B, IL-6, IL-10, MMP-3 (chronic form), and MMP-
9 (chronic form) polymorphisms were significantly associated with the risk of developing
periodontitis, whereas other polymorphisms in the IL-4, IL-8, IL-18, Fcγ, COX-2, MMP-2,
MMP-3 (aggressive), MMP-8, and MMP-9 (aggressive) polymorphisms had no
significant association with risk of developing periodontitis.

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PERIODONTITIS IN GENETIC SYNDROMES AND OTHER
DISEASES
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PAPILLON-LEFEVRE SYNDROME
EHLERS – DANLOS SYNDROME
CHEDIAK HIGASHI SYNDROME
CYCLIC NEUTROPENIA
DOWNS SYNDROME

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PAPILLON – LEFEVRE SYNDROME:

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• PLS has been associated with-
i. Decreased neutrophil chemotaxis
ii. Reduced random neutrophil migration
iii. Impaired neutrophil phagocytosis
iv. Decreased myeloperoxidase activity
v. Increased superoxide radical neutrophil production, associated with a decreased
lymphocyte response to pathogens.

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EHLERS-DANLOS SYNDROME:
• “Dystrophia mesodermalis”, “Fibrodysplasia elastica generalisatica”.

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• “Defective Dentinogenesis”.
• “Ligneous periodontitis”.

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CHEDIAK – HIGASHI SYNDROME:

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CYCLIC NEUTROPENIA:

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DOWNS SYNDROME:

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GENE LIBRARY
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• In humans, approximately 25,000 genes exists among the 3 billion base pairs of DNA in the
genome.
• To study anyone of these genes, a researcher first isolates it from all of the other genes in an
organisms DNA.
• One isolation method has a relatively long history and involves the construction of a DNA
library.
• When a gene is identified and copied, it is said to have been “cloned”.

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• Gene Library is a large collection of DNA fragments cloned from a given organism, tissue,
organ, or cell type.
• It may contain entire genomic sequences or complementary DNA sequences formed from
messenger RNA .
GENE
LIBRARIES
Genomic
library
cDNA
library

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GENOMIC LIBRARY:
• A genomic library is a collection of bacteria which have been genetically engineered
to hold the entire DNA of an organism.
• For the construction of DNA library-
i. Size of the gene
ii. Capacity of the vector
iii. Molecular tools
iv. Vectors

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STEPS OF GENOMIC LIBRARY CONSTRUCTION:

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a. Isolation of DNA from cells
b. Digestion into small fragments
c. Introduction into suitable vectors
d. Insertion into bacteria
e. DNA isolation
f. Collection of Genomic DNA library

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USES OF GENOMIC LIBRARY:
• first step in any DNA sequencing projects.
• helps in identification of the novel pharmaceutically important genes.
• can explore the genome of an organism to learn more about genomic structure and function.
• Gene mapping.
• Useful in Recombinant DNA Technology, helps to genetically modify organisms and produce
clones of desired types.

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GENE THERAPY
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• Gene therapy is a technique for correcting defective genes responsible for disease
development.
• It involves the transfer of a therapeutic or working gene copy into specific cells of an
individual in order to repair a faulty gene copy, which is to cure or to favorably modify the
clinical course of a condition.

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MECHANISM:
A vector delivers the therapeutic gene into a protein target
Target cells become infected with viral vector
Vector’s genetic material is inserted into the target cell
Functional proteins are created from the therapeutic gene
Cells return to a normal state

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GOALS OF GENE THERAPY:
i. Replacing a mutated gene that causes disease with a healthy copy of the gene.
ii. Inactivating or “knocking out” a mutated gene that is functioning improperly.
iii. Introducing a new gene into the body to help fight a disease.

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FUNDAMENTALS OF GENE THERAPY:
• A normal gene may be inserted into a non-specific location within the genome to replace a
non-functional gene.
• An abnormal gene could be swapped for a normal gene through homologous recombination.
• An abnormal gene could be repaired through selective reverse mutation, which returns the
gene to its normal function.
• The regulation ( the degree to which a gene is turned on/off) of a particular gene could be
altered.
• The spindle transfer is used to replace entire mitochondria that carry defective mitochondrial
DNA.

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TYPES OF GENE THERAPY:
i. Germ line gene therapy
ii. Somatic gene therapy

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GENE DELIVERY:
• The preferred strategy for gene transfer depends on the required duration of protein release
and the morphology of the target site production.
• There are various methods for gene delivery:
a) Viral
b) Non-viral.

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VIRAL:
i. Retrovirus
ii. Adenovirus
iii. Adeno - associated virus
iv. Herpes simplex virus
NON-VIRAL:
i. Direct introduction of therapeutic DNA into target cells.
ii. Use of a liposome (artificial lipid sphere with an aqueous core).

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IMPLICATIONS OF GENE THERAPY IN PERIODONTICS:
• In periodontics, currently genetic principles are being applied along with tissue engineering
for periodontal rehabilitation.
• Approaches-
i. Protein-based approach
ii. Cell-based approach
iii. Gene-delivery approach

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PROTEIN-BASED APPROACH:
Growth & differentiation factors are used for regeneration of periodontal tissues like
TGF-β, BMP-2,6,7,12, bFGF, VEGF & PDGF.
CELL- BASED APPROACH:
Several studies using mesenchymal stem cells have demonstrated efficient
reconstruction of bone defect that are too large to heal spontaneously.
GENE DELIVERY APPROACH:
To overcome the short half-lives of growth factor peptides invivo, gene therapy that
uses a vector that encodes the growth factor is utilized to stimulate tissue regeneration.

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1. Gene Therapeutics-Periodontal Vaccination
2. Genetic Approach to Biofilm Antibiotic Resistance
3. An In vivo Gene Transfer by Electroporation for Alveolar Remodeling
4. Antimicrobial Gene Therapy to Control Disease Progression
5. Designer Drug Therapy in Treating Periodontal Disease

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Gene therapeutics-periodontal vaccination:
A salivary gland of a mouse when immunized using plasmid DNA
encoding the Porphyromonas gingivalis (P. gingivalis) fimbrial gene produces fimbrial protein
locally in the salivary gland tissue resulting in the subsequent production of specific salivary
immunoglobulin’s IgA and IgG, antibodies and serum IgG antibodies.
• This secreted IgA could neutralize P. gingivalis and limit its ability to participate in plaque
formation.

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Genetic Approach to Biofilm Antibiotic Resistance:
Mah et al., identified gene ndvB encoding for glycosyltransferase required for the
synthesis of periplasmic glucans in wild form of Pseudomonas aeuroginosa RA14 strain. This
remarkably protected them from the effects of antibiotics and disinfectants.

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An In vivo Gene Transfer by Electroporation for Alveolar Remodeling:
• Using an in vivo transfer of LacZ gene (gene encoding for various remodeling molecules) into
the periodontium and using plasmid DNA as a vector along with electroporation for driving
the gene into cell, has shown predictable alveolar bone remodeling.
• Step A- Cells obtained from outpatient skin biopsy
• Step B- Gene of therapeutic interest is introduced into cells by electroporation
• Step C- Genetically engineered cells are propagated and characterized
• Step D- Genetically engineered cells are returned back to clinician

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Antimicrobial gene therapy to control disease progression:
• Researchers have shown when host cells were infected in vivo with β defensin-2 (HBD-2)
gene via retroviral vector; there was a potent antimicrobial activity which enhanced host
antimicrobial defenses.

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Designer drug therapy in treating periodontal disease:
• If genes necessary for normal development are known, then “designer drug therapies”
aimed at one area of the gene or the other can be developed.
• These designer drugs will be safer than today’s medicines because they would only affect the
defect in a gene clearly identified through genetic research.

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LIMITATIONS OF GENE THERAPY:
i. Difficulty in delivering of gene
ii. Short-lived nature of the gene therapy
iii. Activation of immune response
iv. Chance of inducing a tumor (Insertion mutagenesis)
v. Safety of vector
vi. Difficulty to treat multi gene disorders
vii. Expensive.

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BIBLIOGRAPHY
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 Carranza’s clinical periodontology-11th ed.
 Jan Lindhe, Niklaus P. Lang -6 th; Clinical periodontology and Implant Dentistry.
 Thomas G. Wilson, Kenneth S. Kornman, Fundamentals of Periodontics- 2nd ed.
 Thomas C. Hart & Kenneth S. Kornman, Genetic factors in the pathogenesis of
periodontitis; Perio2000, vol 14, 1997, 202-215.
Kinane FD et al, The genetic basis of periodontitis; Perio2000 ,Vol 39, 2005, 91-117.
Vijayalakshmi R et al, Genetic polymorphisms in periodontal diseases: An overview Indian J
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