The document outlines a comprehensive study on genetics, focusing on heredity, gene structure, and gene expression, with specific emphasis on its relationship to periodontal diseases such as chronic and aggressive periodontitis. It details terminology relevant to genetics, various genetic mutations, polymorphisms, and the types of genetic disorders, while discussing their implications in understanding disease susceptibility and progression. Study designs for examining genetic factors include familial aggregation, segregation analysis, twin studies, and others, highlighting the complexity of genetics in relation to human health.

1. GENETICS,STUDY
DESIGNS
PRESENTED BY
Dr Harshavardhan Patwal

2. CONTENTS
 INTRODUCTION
 TERMINOLOGY
 CENTRAL DOGMA
 STRUCTURE OF GENE
 STUCTURE OF DNA
 STUDY DESIGNS
 STUDIES PERTAINING TO:
◦ CHRONIC PERIODONTITIS
◦ AGGRESSIVE PERIODONTITIS
◦ IMPLANTS
 EPIGENETICS
 FUTURE PROSPECTS

3. INTRODUCTION
 Genetics is defined as the science of heredity .
 The word GENETICS was coined by William Bateson
in 1907
 In 1903 , Walter Sutton and Theodor Boveri
independently proposed that chromosomes carry the
hereditary factors.
 Chromosomal theory of inheritance-Chromosomes
contain the DNA which is the genetic material
 Gregor John Mendel is the father of genetics

4. INTRODUCTION
Mendels laws of heredity;
 Law of segregation -the character of an organism are
determined by pairs of factors of which only one can be
present in each gamete.
 Law of independent segregation-when two or more
pairs of characters are brought together in a crossover
,they segregate independently of each other.
 Periodontitis is a multifactorial disease. While microbial
and other environmental factors are believed to initiate
and modulate periodontal disease progression, there
now exists strong supporting evidence that genes play
a role in the predisposition to and progression of
periodontal diseases.

5. TERMINOLOGY
 Allele – one of several possible alternative forms of a given gene
differing in DNA sequence assumed to arise by mutation and often
affecting the function of a single product. Humans carry two sets of
chromosomes, one from each parent. Single nucleotide
polymorphisms may render two sets of equivalent genes different.
 Alternative splicing – the generation of multiple protein isoforms from
a single gene via the splicing together of nonconsecutive exons during
RNA processing of some but not all of RNA transcripts. Believed to the
mechanism involved with the high number of proteins produced from a
smaller number of genes in humans.
 Autosome – chromosomes other than sex chromosomes.
 Autosomal dominant – the dominant effect of one gene located on an
autosome regardless of the presence of the other, normal copy.
 Autosomal recessive – A gene on an autosome that is required in two
copies to be active in an individual. An individual who carries two such
copies of the same abnormal gene will be subjected to effects from that
gene.

6.  Complementary DNA (cDNA) – the DNA sequence
produced by the enzyme called reverse transcriptase from
messenger RNA. Very frequently used in cloning
experiments.
 Chromosome – a nuclear structure carrying genetic
information arranged in a linear sequence. Humans have 23
pairs (including a pair of sex chromosomes XX or XY).
 Chromatin : Condensation of the DNA with histones and
other chromosomal proteins.Chromatin is further organized
into chromosomes.
 Cloning – the generation of sufficient copies of a target DNA
sequence that allows it to be sequenced or studied further.
 Dizygotic twin – fraternal twins as a result of fertilization of
two separate eggs. They are no more similar genetically than
are siblings.
 Exon – the expressed portion of DNA or RNA that will
ultimately be translated into protein. Multiple exons are

7.  Frameshift mutation – A type of mutation as a result of an insertion
or deletion of one or more nucleotides into a gene causing the
coding regions to be read in the wrong frame.
 Gene – a hereditary unit that occupies a specific position (locus)
within a genome or chromosome that has one or more specific
effects upon the phenotype of the organism.
 Gene expression – the process involving use of the information in a
gene via transcription and translation leading to production of a
protein affecting the phenotype of the organism determined by that
gene.
 Genetic code – in RNA and DNA, the consecutive nucleotide triplets
(codon) that specify the sequence of amino acids for protein
synthesis (translation).
 Genome – a term used to refer to all the genes carried by an
individual or cell.
 Genotype – the genetic makeup of an organism or cell distinct from
its expressed features or phenotype.

8.  Homozygous – the presence of identical alleles of one or more
specific genes (e.g. A/A).
 Heterozygous – the presence of differing alleles of one or more
specific genes (e.g. A/B).
 Intron – the intervening (non-coding) portion of DNA or RNA that is
removed during RNA processing.
 Isoforms – a protein with equivalent function and similar or
identical sequence but derived from a different and usually tissue-
specific gene.
 Linkage – the tendency for certain genes to be inherited together
due to their presence on the same chromosome.
 Linkage disequilibrium – the occurrence of some genes together
more often than would be expected by random distribution.
 Locus (plural loci) – the physical location a gene occupies within a
chromosome or portion of genomic DNA.

9.  Monozygotic twin – identical twins having identical sets of nuclear genes
as a result of separation of blastomeres.
 Mutation – alteration of the genomic sequence compared to a reference
state. Not all mutations have harmful events (silent mutation).
 Phenotype – the observable characteristics displayed by an organism as
influenced by environmental factors and independent of the genotype of the
organism.
 Polymorphism – a region on the genome that varies between individual
members of a population present in a significant number of individuals.
 Single nucleotide polymorph (SNP) – a polymorphism caused by the
change in a single nucleotide believed to be the most common genetic
variation between individual humans.
 Splicing – the removal of introns from transcribed RNAs. The removal of
exons results in the formation of ‘splice variants’ or ‘alternatively spliced’
protein isoforms allowing different proteins to be produced from the same
initial RNA or gene.
 X-linked disease – a disease of genetic origin as a result of a mutation on
the X-chromosome.
 Wild type – the non-mutated, naturally-occurring form of a gene.

10.  Diseases with etiologies that include both genetic and
environmental factors are refferred to as multifactorial.
 Genetic marker refers to any gene or nucleotide sequence
that can be mapped to a specific location or region on a
chromosome.
 Trait and disease might be caused by a single gene
(monogenic), several genes (oligogenic), or many genes
(polygenic).
 In monogenic disorders, genes are referred to as causative
because almost everyone with the mutation develops the
condition.
 Environmental factors generally play a minor role in
determining the phenotype. In contrast, genes involved in
complex multifactorial disease are called susceptibility genes.

11. HUMAN GENOMIC PROJECT
 Early in 2001, man heralded one of the greatest
scientific achievements-a draft of the human
genome.
 The human genome contains 30,000-40,000
genes.(Baltimore,2001)
 In periodontics genetics of both humans and
pathogens and the interaction between them is
studied.
 Presently the complete sequence of P.gingivalis
has been sequenced.

13. CHROMOSOME
Waldeyer in 1888 coined the term
chromosome
Chromosome consists of:
 70%-protein
 20%-DNA
 10%-RNA

14. GENE
 1st proposed by MENDEL in 1865 he
called it as factor .
 The word gene was coined by
JOHANNSON in 1909

15. Promoter – Sequence of nucleotide left (upstream) of the
coding region starting with nucleotide position -1(not as
triplets)
Coding region –Reading frame starting at nucleotide Position
+1 containing triplets or codon.
 Exons – (true coding region ) - nucleotide bases
contained in noncontiguous segments called the
EXONS(expressed sequences).
 INTRONS(non coding region) - Exons are separated by
other sequences not present in mature mRNA called
INTRONS (intervening sequences).

16. DNA
 Discovered in 1953 by Watson and
Crick by X ray diffraction pictures

17. CENTRAL DOGMA

18. CENTRAL DOGMA

21. Transcription requires
 DNA template
 RNA polymerases I, II, III.
 Transcription factors
GENE
TRANSCRIPTION(Lewin,1994)

22. Factor chart

23. TRANSCRIPTION FACTORS:
CLASSIFIED
 Based on action (Papavassiliou,1995)
1. Basal factors – To initiate transcription on the correct site.E.g.., TATA
box-binding proteins (TBP), Polymerase II Transcription factors
(TFIIA,TF IIB,TFIIE,TFIIF).
2. Upstream factors – recognize specific DNA elements located
upstream of the transcription start site.
3. Inducible factors - important regulators of gene transcription, eg
hormones, growth factors act through this

24. Based on structure(Johnson &
McKnight,1989)
1. Zinc finger proteins e.g.steroid receptors
zinc ion bound to 2 cysteines and 2 histidines
2. Leucine zipper proteins
products of c-fos and c-jun protooncogenes
3. Homeodomain proteins
4. Helix-loop-helix(HLH) family proteins – important
in the regulation of metabolism, cell differentiation

25. TRANSCRIPTION

26. mRNA

27. mRNA Processing
1. Capping (Sacchs,1993)
2. Polyadenation(Wahl & Keller,1996)
3. Splicing(McKeown,1992)

29. RIBISOMES

30. STEPS IN TRANSLATION
1. INITIATION
2. ELONGATION
3. TERMINATION
4. RELEASE OF PEPTIDES

37. The ribosome reads 3 nucleotides at a time (CODON).The ribosome
looks for the start codon where it begins building the aminoacid
chain.
There are 64 possible codons. One amino acid may be specified by
one or more codons.
Three codons do not specify any amino acid, they are stop codons.

38. tRNA’s have an ANTICODON on one end and an AMINOACID on the
other.
The anticodon dictates which aminoacid it carries to the ribosome.
The aminoacids are transferred to the ribosome by t-RNA molecules.

39. The ribosome reads the next codon and another tRNA with anticodon binds.

40. POST-TRANSLATIONAL MODIFICATION
Protein folding and glycosylation
 Folding of nascent polypeptides into 3-
dimensional structures is assisted by accessory
proteins and disulphide linkages, molecular
chaperones(BIP,HSP,FO).
 Modifications such as hydroxylation of
proline and hydroxyl residues in collagen can
occur only on unfolded polypeptides.

41. SORTING OF PROTEINS
The movement of protein from the site of
protein synthesis to a different destination
is known as targeting or
sorting.(Heijne,1990)
TRANSLOCATION
The movement of polypeptide across
membranes of organelles and RER .This is
followed by secretion of protein and then
undergoing removal of extra
sequences(Processing)

42. FACTORS THAT AFFECT PROTEIN
PRODUCTION
1. DNA methylation – mechanism by which gene
expression is regulated.(Eden,1994)
2. Methylated genes are inactive and the promoter activity
is inhibited.
3. Most environmental and physiological mediators affect
gene transcription by modifying the synthesis of
transcription factors.(Maniatis et al,1987)
 Synthesis of new transcription factors when needed
 Covalent modification of aminoacids and phosphorylation of
certain residues modifies the binding of this particular
transcription factor to the DNA response sequences.
 Many hormones, cytokines act by phosphorylation of the
transcription factor API
 Steroid hormones, Vit D, sex hormones bind to their respective
cytoplasmic DNA binding receptors.

43. GENETIC VARIANCES
 Genes can exist in different forms or
states (alleles)
 Allelic variants of a gene differ in their
nucleotide sequences.

44. ALLELE
 A variant of the DNA sequence at a given
locus is called an allele.
 The genotype for each gene comprises
the pair of alleles present at that locus
 Allele that leads to an observable
phenotype –dominant allele
 Allele does not lead to an
observable phenotype- recessive
allele.

45. MUTATION
 Mutation can cause variation in
alleles.
• A mutation is defined as a heritable
alteration or change in the genetic
material.

46. Basis of classification Types
Origin Spontaneous
•Tautomerism
•Depurination
•Deamination
•Slipped Strand Pairing
Induced
•Chemical
•Radiation
•Viral infections
Cell type Germ line – reproductive cell(Hereditary disease)
Somatic- somatic cell(Cancer,Congenital malformations)
Stability Fixed
Substitution-base pair change
Transition - Pyrimidine to pyrimidine (T or C) / purine to
purine (A or G).
Transversion- Pyrimidine to purine / purine to
pyrimidine
Insertion: extra nucleotide
Deletion- missing nucleotide.
Dynamic
Trinucleotide repeat mutation

47. Basis of classification Types
Effect on translation Synonymous mutation
Silent
Non Synonymous mutation
Missense
Nonsense
Frameshift
Substitution/Addition of
nucleotide
Point Mutation
Silent
Missense
Nonsense
Frameshift Mutation
Insertion
Deletion
Effect on function Loss of function- Null
Neomorphic-Gain in function
Antimorphic mutation
Hypomorphic- reduced function.
Hypermorphic- increased function
Ectopic expression
Lethal mutation
Reversion

48. Polymorphism
 Allele is a variant form of a gene
 The coexistence of multiple alleles at a locus is called “Genetic
polymorphism” when they occur at more than one percent in a
population.

49. Types of Polymorphism
 SNP: Single Nucleotide polymorphisms-
The change in a single nucleotide found
at a single location is called SNP.
 VNTR: Variable number of Tandem
Repeats.-Repeated base patterns
consisting of several hundreds of base
pairs
 STR: Simple Tandem repeats.-2,3 or 4
nucleotide repeats on a variable number
of locations.

50. MODIFYING DISEASE GENES FOR WHICH GENE
POLYMORPHISM IS RISK FACTOR FOR
PERIODONTITIS
 ACE genes
 CARD15
 CCR5
 CD14
 ER2
 ET1
 FBR gene
 Fcγ receptor gene
 N-formyl peptide receptor
gene
 IFNGR1
 Interleukin-1 alpha and
beta gene IL-receptor
antagonist
 Il2.4,6,10
 LTA
 MMP-1,3,9
 MPO
 NAT2
 PAI1
 RAGE
 TGFB
 TIMP2
 TLR2,4
 Vitamin D receptor
 HLA genes
 N-acetyltransferase
 TNF-β and TNF-α gene

51. Polymorphism Vs Mutation
MUTATIONS POLYMORPHISMS
Here a single gene locus causing
mutation has a major
physiological impact & considered
to be deterministic to disease.
Here the gentic alteration that
contributes to complex disease
has smaller effect.
Seen less commonly in the
population
Atleast or more than 1% of
population.
Mutation have causually linked
with Mendelian disease.
Here mutation is not causually
linked to disease but alleles are
seen more frequently in disease
individuals.
One-to-one correlation of a
mutation & disease can be
established.
No one-to-one correlation.

52. 3 Major Categories of Genetic
Disorders
1. Major chromosomal disorders
2. Mendelian disorders
3. Non-Mendelian disorders

53. Major chromosomal disorders
 Numerical Abnormality
◦ Aneuploidy
◦ Polyploidy
◦ Monosomy
◦ Trisomy
◦ Mosaicism-2 or more population of cells
 Structural Abnormality
◦ Translocation
◦ Isochromosomes
◦ Inversions
◦ Deletion
◦ Insertion
◦ Ring Chromosome

54. "Simple" Mendelian diseases
 Diseases that follow predictable and generally
simple patterns of transmission have been called
"Mendelian" conditions. Genes involved are called
as causative genes.
 The name reflects the fact that these diseases
occur in simple patterns in families, and in most
cases a single gene locus is the major determinant
of the clinical disease phenotype.
 These diseases follow a classic Mendelian mode of
inheritance:
 Autosomal dominant-Huntington disease
 Autosomal recessive-Cystic Fibrosis
 x-linked dominant- Aicardi Syndrome
 x-linked recessive - Hemophilia A

55. SYNDROMES ASSOCIATED WITH
PERIODONTITIS(Simple Mendelian Diseases)
Condition Biochemical/tissue defect Inheritance Periodontal
Disease
Papillon Lefevre Syndrome Cathepsin C Autosomal
recessive
AP
Halm Munk Syndrome Cathepsin C Autosomal
recessive
AP
Ehlers Dalnos Syndrome Type
IV
Collagen Autosomal
Dominant
AP
Ehlers Dalnos Syndrome 8 Collagen Autosomal
dominant
AP
Cyclic Neutropenia Neutrophil Elastase Autosomal
Dominant
AP, CP
Chronic Familial Neutropenia Defect unknown Autosomal
dominant
AP, CP
Chediak Higashi Syndrome Lysosomal trafficking
regulator gene
Autosomal
recessive
AP
Congenital disorder of
glycosylation Type 11C
Glucose diphosphate fucose
transporter 1
Autosomal
recessive
AP
Leukocyte adhesion deficiency Leukocyte chain adhesion Autosomal AP, CP

56. Multifactoprial Diseases or
Complex" diseases
 Genetically complex diseases are
much more prevalent (>1% of
population) and is caused by
susceptibility genes
 This type is the result of the interaction
of multiple different gene loci.
Additionally, environmental factors are
important in the disease process.
 Example:Periodontitis,

57. STUDY DESIGNS
1. Familial Aggregation
2. Segregation Analysis
3. Twin Studies
4. Linkage Analysis
5. Association Studies

58. Familial Aggregation
 Familial aggregation of a trait or disease can
suggest genetic etiology.
 However, families also share many aspects
of a common environment, including diet and
nutrition, exposures to pollutants, and
behaviors such as smoking (active and
passive).
 Certain infectious agents may cluster in
families. Thus, familial aggregation may result
from shared genes, shared environmental
exposures and similar socioeconomic
influences.
 To determine the evidence for genetic factors
in familial aggregation of a trait, more formal
genetic studies are required.

59. Familial Aggregation
AUTHOR,YEAR SUBJECTS FINDINGS
Chung 1977 In a Hawaii racially mixed
populations. A total of 939
subjected from 241 nuclear
families was included in the
analysis.
Sex, age, years of education and
smoking were significantly
associated. No significant
contribution of genotype to
susceptibility for periodontitis .It was
concluded that common family
environment was a determining
factor of variability in pdl health.
Beaty et
al.1993
Studied familial aggregation of
plaque index, gingival index
and attachment loss. The
sample included 178 volunturs
from 75 families (mostli
African-Americans)and was
mainly block females < 40
years.
Genotype influences plaque index,
but not GI and attachment loss.
Mother offspring correlation was
stronger than father for both GI and
attachment loss.

60. Segregation analysis
 Pattern of transmission of disease through generation is studied in
different families.
 It is compared with those expected under various models of inheritance
to select the best fitting model.
 The pattern in which disease is transmitted across generations
depends on whether disease alleles:
• Lie on autosome/sex chromosomes
• Dominant or recessive
• Fully or partially penetrant.
Adv: Can assess whether the disease gene is autosomal or sex linked,
recessive or dominant.
Limitation:
1. It has low power to resolve heterogeneity (Multiple causes)
2. Cannot distinguish between genetic & environmental influences.
3. Does not provide information about specific genes

62. Author Study Results
Beaty TH et al 1987 Proband with Juvenile
periodontitis- 28 families.
Different models of
inheritance studied
Autosomal recessive mode
of inheritance for JP
Hart TC, Marazita ML et al
1992
Re-interpretation of X-
linked mode of inheritance
among Juvenile
periodontitis
Female ascertainment bias
and lack of father to son
transmission interpreted in
a different way.
Marazita ML et al 1994 EOP- 104 probands- 100
families, blacks and non
blacks families
Autosomal dominant mode
of inheritance among
blacks and non blacks with
70% penetrance
Marazita ML et al 1996 Segregation analysis of
IgG2 levels in EOP among
african americans and
caucasians
Autosomal co-dominant
mode of inheritance
Hodge PJ et al 2000 Caucasian family from
Europe with EOP
Autosomal dominant or X-
linked mode of inheritance
De Carvalho FM et al 2009 Aggressive periodontitis-
Brazilian population
Semi general mode of
transmission: few loci with
small effects contribute to

63. Twin Studies
 Influence of genetic and environmental factors
on complex diseases can be estimated.
 Sir Francis Galton in 1875 was the first scientist
to use this concept.
 Monozygotic twins: 100% similar genetic make
up.
 Dizygotic twins: 50% similar genetic make up
 Heritability estimate can be made.
 Concordance – degree of similarity between
twins in one or more characteristics.
 Discordance- degree of dissimilarity between
twins in one or more characteristics.

64. Two Types:
1. Classic twin study -monozygotic and
dizygotic twins are Reared together
and compared.
2. Monozygotic twins reared
apart:MZA-Effects of shared genes
without the confounding effects of a
common family environment

65. Author Study Results
Corey LA et al 1993 4908 twin pairs:
questionnaire based
study- history of
periodontal disease. 116
MZ twin pairs and 233
DZ pairs
Concordance rate of MZ
twins: 0.23 to 0.38 and
for DZ twins: 0.08 to 0.16
Michalowicz et al 1999 169 twin pairs: presence
of P.ging, A.a,
P.intermedia,
E.corrodens,
F.nucleatum
P.ging-11%, A.a- 22%,
P.intermedia- 19%,
E.corrodens- 0.34%,
F.nucleatum-40%. No
difference in
concordance rates
between MZ and DZ
pairs.
Michalowicz BS et al
2000
64 MZ, 53 DZ twin pairs:
influence of smoking and
utilization of dental
services
Chronic periodontitis-
50% heritability
independent of smoking
and dental services.

66. Linkage Analysis
 Used to map disease allele to specific regions on the chromosomes.
 Linkage studies use sets of families with multiple affected
individuals.
 Complex statistical models are used to determine whether the
marker allele and disease co segregate in the families under a
given inheritance model.
 Linkage can be detected if the marker and disease alleles are
within 20-30 centimorgans of one another.
 LOD(Logaritham of odds) score - Compare the likelyhood of two
genes are indeed linked to the likely hood of observing this data purely
by chance.
Positive LOD score- presence of linkage
Negative LOD score-less likely

67. Linkage studies usually start by identifying markers (SNPs) on a section of a
chromosome and then narrowing the region down until the gene or gene
variant of interest is identified.
DISADVANTAGE-Complex diseases are due to combined effects of
“multiple genes of minor effect”.

68. Example:
Author Study Results
Boughman et al 1986 Localized Aggressive
periodontitis
AgP segrgates with
dentinogenesis
imperfecta. Localized to
long arm of chromosome
4 near the gene for
dentinogenesis
imperfecta.
Li Y et al 2004 Localized Aggressive
periodontitis
Disease gene localized
to chromosome 1.
Tabeta K et al 2009 Linkage disequilibrium
block analysis- SNP’s
and Microsatellites in
chromosome 19
A single microsatellite
marker allele 17 of 1902
G 31 on chromosome
19- associated with
severe chronic
periodontitis

69. Association Studies
 Frequency of marker alleles at a given locus is
compared between subjects with disease(cases) and
healthy controls sampled from same population .
◦ Population based approaches
◦ Family based approaches
 Association suggest that the presence of an
allele confers risk for disease within a defined
environment.
 Limitation –Association does not necessarily imply a
biologic link between the disease and the tested allele.

70. FAMILY STUDIES
AUTHOR,YEAR SUBJECTS FINDINGS
Chung 1977 In a Hawaii racially mixed
populations. A total of 939
subjected from 241 nuclear
families was included in the
analysis.
Sex, age, years of education and
smoking were significantly
associated. No significant
contribution of genotype to
susceptibility for periodontitis .It was
concluded that common family
environment was a determining
factor of variability in pdl health.
Beaty et
al.1993
Studied familial aggregation of
plaque index, gingival index
and attachment loss. The
sample included 178 volunturs
from 75 families (mostli
African-Americans)and was
mainly block females < 40
years.
Genotype influences plaque index,
but not GI and attachment loss.
Mother offspring correlation was
stronger than father for both GI and
attachment loss.

71. TWIN STUDIES
AUTHOR,YEAR SUBJECTS FINDINGS
Ciancio et
al.1969
Investigated levels of gingival
recession and crevice depth and
indices of gingivitis, supra gingival
plaque and calculus in 26 twin pairs
aged 12-17 years .
found no evidence of genetic
influence
Michalowicz
et al 1991
To estimate the genetic variance for
alveolar bone height. Panoramic
radiographs were obtained from 120
pairs of adult twins (mean age = 40.4
years, S.D. = 10.4 years), for
comparison of 62 pairs of MZT ,25
like-sexed DZT and 33 pairs MZA.
The intraclass correlations
MZT = 0.70, DZT = 0.52, and
MZA = 0.55. Significant
genetic variance in the
population for proportional
alveolar bone height.
Corey LA et
al 1993
4908 twin pairs: questionnaire based
study- history of periodontal disease.
(VIRGINIA)116 MZ twin pairs and
233 DZ pairs
Concordance rate of MZ twins:
0.23 to 0.38 and for DZ twins:
0.08 to 0.16

72. TWIN STUDIES
AUTHOR,YEAR SUBJECTS FINDINGS
Michalowicz
et al 1991
Examined the relative contribution of
environmental and host genetic factors to
clinical measures of periodontal disease
through the study 110 pairs of adult twins
(mean age 40.3 years), including 63 MZT
and 33 DZT and 14 MZA
Significant genetic
component for gingivitis,
PD ,CAL, plaque..
38% to 82% of the
population variance for
these periodontal
measures of disease may
be attributed to genetic
factors
Michalowicz
et al 1999
169 twin pairs: presence of P.ging, A.a,
P.intermedia, E.corrodens, F.nucleatum
P.ging-11%, A.a- 22%,
P.intermedia- 19%,
E.corrodens- 0.34%,
F.nucleatum-40%. No
difference in concordance
rates between MZ and DZ
pairs.
Michalowicz
BS et al 2000
64 MZ, 53 DZ twin pairs: influence of
smoking and utilization of dental services
Chronic periodontitis- 50%
heritability independent of

73. ASSOCIATION STUDIES
AUTHOR,YEAR SUBJECTS FINDINGS
Kornman et
al.1997
“Composite” IL-1 genotype consisting of at least
one copy of the more rare Allele at both an IL-1
& and IL – IB loci was associated with severe
periodontitis in northern European adults.
Association-18.9
Gore et
al.1998
Composite genotype in caucasians More rare IL-1β
sites were in linkage
disequilibrium,

74. ASSOCIATION STUDIES
AUTHOR,YE
AR
SUBJECTS FINDINGS
Kobayashi
et al.1997
Neutrophil IgG receptor with CP in
Japanese population
Association was found with
FCᵧRIIIb-NA2
Engebrets
on et al.
1999
IL-1 composite genotype in US
population
Elevated levels of IL-1 Beta
in GCF.
Galbreuth
et al. 1998
TNF genotypes were determined in 32
Caucasian patients with adult
periodontitis and 32 orally-healthy
matched controls, and correlated with
TNF-alpha production by oral
polymorphonuclear leukocytes (PMN)
No association between CP
and TNF-α
1 genotype was correlated
with elevated TNF-α
production by oral PMNs in
patients with advanced
disease. Polymorpheisms.
Armitage
et al 2000
Association of CP with Composite
genotype in Chinese Population
No association

75. AGGRESSIVE
PERIODONTITIS

76. PEDIGREE ANALYSIS
AUTHOR,YEAR SUBJECTS FINDINGS
Benjamin et
al., 1967
Twelve families (52 individuals) XD mode. The
female to male ratio
was
3:1
Butler 1969 A family The proband and his sister had JP. His
mother and maternal aunt and grandfather had
become edentulous at an early age
XD mode
Fourel, 1972 A family (more than 20 individuals) AR mode
Jorgenson et
al., 1975
A family AR mode
Melnick et al.,
1976
Two families
Family 1: five of six siblings, three of them
female, had JP
Family 2: four of eight siblings, all females, had
XD mode with
decreased
penetrance.
The female to male

77. AUTHOR,YEAR SUBJECTS FINDIN
GS
Sussman et
al., 1978
Proband, 17, female .Mother and grandmother were
affected
AD
mode
Vandesteen et
al., 1984
A family (29 individuals in the pedigree trees) The proband
and six siblings all had JP; both parents were edentulous
since early adulthood; both maternal grandparents and at
least two siblings of the mother
had been affected Paternal side: two of the fathers siblings
were affected, but the paternal grandparents were not
affected
XD
mode
Spektor et al.,
1985
One large family (40 individuals in the pedigree trees) The
proband had JP Father (healthy) mother (affected)
Twelve siblings (six affected, six
unaffected) Both maternal grandparents of the proband
had become edentulous at an early
age. Four of 10 siblings of the probands mother had EOP.
The paternal grandparents did not have EOP and
periodontitis was not unusually prevalent in the siblings of
the probands father
XD
mode
Page et al., A family (six individuals) The parents had JP in their teens, XD

78. SEGREGATION ANALYSIS
AUTHOR GENETIC ANALYSIS SUBJECTS FINDINGS
Melnick
et al.,
1976
Segregation
analysis and
pedigree analysis
Two families
Family 1: five of six siblings,three of them
female, had JP
Family 2: four of eight siblings,all females,
had JP
Caucasian & African -American
XD mode
Saxen,
1980
Simple
segregation
analysis
Thirty-one families (158 subjects: 60 parents,
64 siblings and 3 children) Neither parents
nor the children were affected with JP. 11 ⁄ 64
siblings were affected
Finnish group
AR mode
Saxen
et al.
1984
Simple
segregation
analysis
Thirty families (60 parents and 52
siblings).No parents were affected;9 ⁄ 52
siblings were affected(Finnish group)
AR mode
Beaty
et al.,
1987
Complex
segregation
analysis
Twenty-eight families (372 individuals: 62
had JP, 95 were unaffected and 215
unknown)(US Sample)
AR mode
Long Complex 33 families (199 individuals)Compared the AR mode

79. SEGREGATION ANALYSIS
AUTHOR GENETIC
ANALYSIS
SUBJECTS FINDINGS
Boughma
n et al.,
1988
Complex
segregation
analysis
28 families (372 individuals: 62 had JP,95
were unaffected and 215 unknown)(Triracial
isolate)
AR mode
Marazita
et al.,
1994
Complex
segregation
analysis
One-hundred families (631 individuals in
total)
African–Americans
Dominant
mode
with
penetranc
e of about
70%
Hodge et
al., 2000
Segregation
analysis
and linkage
study
A large family (40 individuals
in the pedigree trees)
North European Caucasians
Dominant
mode

80. TWIN STUDY
 No twin study on aggressive
periodontitis has been reported

81. LINKAGE ANALYSIS
AUTHOR GENETIC
ANALYSIS
SUBJECTS FINDINGS
Boughma
n et al.,
1988
Linkage
study
A large, five-generation family
from southern Maryland
(more than 70 individuals)
An AD mode of JP: its
localization to chromosome 4
and linkage to dentinogenesis
imperfecta and Gc
Hart et
al., 1993
Linkage
study
Fifteen African–American and
four Caucasian families (228
individuals)
Exclusion of the 4q candidate
region for EOP
Li et al.,
2004
Linkage
study
Four African–American
families (28 subjects)
L-AgP is linked to human
chromosome 1q25

82. ASSOCIATION ANALYSIS
AUTHOR GENETIC
ANALYSIS
SUBJECTS FINDINGS
Diehl et
al.,1999
Family-
based
associatio
n
study
Twenty-eight African–
American and seven
Caucasian–American families
(285 individuals with DNA
available for 246)
Allele 1 of both interleukin-
1A-889 and interleukin-1B
+3953 was transmitted more
frequently with the EOP
phenotype
Ren et
al.2009
Family-
based
associatio
n
study
Seventy-three nuclear
families
(DNA available for 204
subjects) from China
Allele A of S100A8 gene SNP
rs3795391 (A ⁄ G) showed
significantly preferential
transmission to the AgP-
affected
individuals in the
additive genetic model

83. GENETICS & IMPLANTS
 Very few studies have been reported addressing the influence of
genetics on implant survival.
 Wilson et al.1999 . Studied the effects of the IL-1 genotype,smoking
status, and patient’s age on failed or failing implants was compared to
successfully integrated implants .Statistical testing failed to indicate a
relationship between implant failure, age, or IL-1 genotype status.
 Rogers et al.2003. also failed to demonstrate a relationship between
implant failure and the IL-1A (-899), IL-1B (+3953) composite genotype
in Caucasian patients.
 [
 Systematic review by Huynh et al.2007on the role of the composite
interleukin-1alpha and interleukin-1beta polymorphisms and their
natural specific inhibitor, interleukin-1 receptor antagonists, with
respect to the development of periodontitis and periodontal therapy ,
no conclusive evidence can be attributed to the genetic traits.

84. EPIGENETICS
 Epigenetics is the study of changes produced in gene
expression caused by mechanisms other than changes in the
underlying DNA sequence 2 Major Mechanism are:
◦ DNA Methylation
◦ Histone Modification
 The hypo or hyper methylation of sites upstream of promoter region
of cytokine genes can regulate the gene expression thereby
resulting in increased production of the cytokines.
 Chung et al ,2003 has demonstrated for TNF alpha in Rheumatoid
arthritis.
 Oral infection may also lead to epigenetic alterations, locally within
gingival tissue or more globally with widespread effects. Technology
is available to determine genomic-wide epigenetic changes that can
be applied to study tissues at the biofilm interface to compare
diseased tissue to healthy control tissue.

85. Susceptibility profile
 Combination of gene polymorphisms
constitute a profile.
 Help to classify patients as low,
medium and high risk.
 Already in application in systemic
disease such as Alzheimer’s disease .
FUTURE PROSPECTS

86. Screening for risk assessment
 Aggressive periodontitis: screening
the siblings of “probands” for
aggressive periodontitis.

87. References
 Clinical Periodontology. Carranza, 10th edition.
 Clinical Periodontology and Implant dentistry. Lindhe,
4th edition.
 Biology of the Periodontal Connective
Tissues.Naraynan AS, Bartold PM
 Genes and gene polymorphisms associated with
periodontal disease. Crit Rev Oral Biol Med. 2003:
14(6); 430-449.
 The genetic basis of periodontitis. Kinane DF, Hart TC.
Periodontology 2000, 2005; Vol 39: 91-117.

88.  Genetic study of families affected with
aggressive periodontitis.Huanxin et al.
Periodontology 2000, 2011; Vol 56: 87-101.
 The genetic relationship to periodontal
disease.Nares.S. Periodontology 2000, 2003;
Vol 32: 36-49.
 Epigenetic Regulation of gene expression in
the inflammatory response and relevance to
common diseases.Wilson AG.J Periodontal
2008;79:1514-1519.

89.  Gene polymorphisms in periodontal health and
disease. Perio-2000. 2006: 40; 94-106.
 Clinical utility of a genetic susceptibility test for severe
chronic periodontitis – A critical evaluation. JADA
2002: 133; 452-459.
 Implications of Genetic Technology for the
Management of Periodontal Diseases. JP 2005: 76;
850-857.