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![CTSC gene which was observed in 8 families and was found that these mutations
resulted in complete loss of enzyme.[Hart et al 1999].
CTSC mutations have also been identified in families with prepubertal periodontitis .
It has also been found that polymorphic functional variants of CTSC may be involved
in more common type of aggressive periodontitis.
Papillon lefevre syndrome](https://image.slidesharecdn.com/geneticfactors-191219153412/75/Genetic-factors-25-2048.jpg)
![Decreased expression of ANRIL is correlated with decreased expression levels
of ADIPORI, VAMP3 and C11ORF10. [Bochenek et al 2013]
Protein VAMP3 belongs to VAMP/synaptobrevin family and plays a role in
phagocytosis wherein VAMP3 mediates the transfer of TNF to cell surface
[Murray et al 2005]
VAMP3 gene polymorphisms](https://image.slidesharecdn.com/geneticfactors-191219153412/75/Genetic-factors-51-2048.jpg)
![Risk gene of aggressive periodontitis GLT6D1 mapped to
chromosome 9 at 9q34.3 [ Schafer et al 2010].
It encodes for an unknown protein belonging to family of
proteins that is characterized by a glycosyl transferase domain 1 .
Mainly expressed in gingiva and T cells.
GLT6D1 gene polymorphisms](https://image.slidesharecdn.com/geneticfactors-191219153412/75/Genetic-factors-53-2048.jpg)
![Late failures in implant dentistry
Rogers et al
2002 laine et
al 2006
Studies reported on IL1A -889, IL1B -511, IL1B +3954 and IL1RN VNTR
polymorphisms separately in association with late implant failures.
Feloutzis et al
2003
-In a study of 90 Caucasian patients were investigated for peri-implant
bone loss at time of re-examination [mean 5.6 years]
-28 patients carrying IL1 composite genotype were stratified in to non-
smokers , former smokers and heavy smokers
-Heavy smokers were found to have more annual bone loss.
Gruica et al
2004
IL1 composite genotype and smoking were significantly associated with
peri-implant bone loss after 8 years in function among Caucasians.](https://image.slidesharecdn.com/geneticfactors-191219153412/75/Genetic-factors-60-2048.jpg)
![Evidence for the role of genetics in periodontitis
A study was done on 77 siblings of 39 probands with LJP and GJP and it was found that 50 %
of siblings suffered from JP. 11 families a co-occurrence of LJP and GJP was present.
[Boughman et al 1992].
A family with 527 subjects: 60 with LJP,72 with GJP ,254 unaffected subjects and 141 with
unknown periodontal condition in Caucasians and African American families. The authors
concluded that the most likely mode of inheritance was autosomal dominant in both
American and Caucasian with penetrance of 70% in African americans and 73 % in
Caucasians.[Marizata et al 1994]
Aggressive periodontitis](https://image.slidesharecdn.com/geneticfactors-191219153412/75/Genetic-factors-61-2048.jpg)
![Chronic periodontitis
A study was done in 75 families consisting of 178 subjects to determine familial aggregation
.The results showed both gingival index and attachment loss showed a stronger correlation
between mothers and offspring compared with fathers and offspring.[Beaty et al 1993]
A study analysed periodontal condition in an untreated population in Guatemala consisting of
109 siblings from 40 nuclear families with an age range of 35-60 years. They failed to show
familial clustering for periodontal disease.[Dowsett et al 2002]
A study was done in 78 subjects and was found that significant sibling relationship effect on
plaque, calculus and loss of attachment but not for pocket depth.[van der Velden et al 1993]](https://image.slidesharecdn.com/geneticfactors-191219153412/75/Genetic-factors-62-2048.jpg)
Uploaded byRamya Ganesh
Genetic factors
This document summarizes genetic factors associated with periodontitis. It discusses various genetic studies related to chronic and aggressive periodontitis, including studies on gene polymorphisms like IL1, TNF, FCγR, IL10, and others. It also covers genetic terminology, types of genetic studies like twin studies, family studies, case-control studies and genome-wide association studies. Specific gene mutations linked to syndromes associated with periodontitis are mentioned.
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Genetic factors
- 1. GENETIC FACTORS ASSOCIATEDWITH PERIODONTITIS DR RAMYA GANESH SENIOR LECTURER MALABAR DENTAL COLLEGE AND RESEARCH CENTRE
- 2. CONTENTS• INTRODUCTION • TYPEOF GENETIC STUDIES • STUDIES RELATED TO CHRONIC PERIODONTITIS • STUDIES RELATED TO AGGRESSIVE PERIODONTITIS • IL1 GENE POLYMORPHISMS • TNF GENE POLYMORPHISMS • FCϒR GENE POLYMORPHISMS • IL10 GENE POLY MORPHISMS • ANRIL • CAMTA1 • GLT6D1 • COX2 • NPY • VIT D RECEPTOR • IMPLANT FAILURE GENES • REFERENCES
- 3. INTRODUCTION Association of periodontitiswith a genetic component was first found in 1965 and studies were carried out extensively from 1990’s Diseases are associated with variations in multiple genes each having a small overall contribution for developing disease process. Presence of genetic risk factors directly increases the probability of periodontal disease development.
- 5. Genetics is definedas the science of heredity primarily concerned with understanding biological properties that are transmitted from parent to offspring. GENETICS Transmission genetics Molecular genetics Population genetics Quantitative genetics
- 6.
- 7.
- 8. Gene Is the basicunit of heredity that occupies a specific position (locus) on a chromosome and has specific effect on the phenotype of the organism.
- 9. Chromosome A chromosome isan organized structure containing DNA
- 10. Allele Variations in thenucleotide sequence at a locus.
- 11. Autosome A chromosome thatis not a sex chromosome Dominance : Relationship between alleles of one gene, in which the effect of one allele masks the contribution of a second allele on the same locus
- 12. Exon Protein coding regionsof DNA Intron A DNA region within a gene that is not translated to protein
- 13. Gene expression The processby which information in a gene is utilized via transcription and translation leading to production of protein.
- 14. Traits In genetics, atrait refers to any genetically determined characteristic.
- 15. Mutation Changes in DNAsequence of genome can result from errors that occur during DNA replication or meiosis and can be caused by radiation, viruses, mutagenic chemicals. Microsatellite markers Are di-, tri-, or tetra nucleotide tandem repeats in DNA sequences.
- 16. Dizygotic twins Twins thathave resulted from fertilization of two separate eggs. They are no more similar to each other than are non twin siblings. Monozygotic twins twins with identical genetic make up as a result of fertilization of a single egg that splits in to two embryos.
- 17. Concordance The probability thata pair of individuals (eg twins) both have a certain characteristic ( eg periodontal disease). Penetrance The proportion of individuals who have a particular allele / genotype who express an associated trait (phenotype) Probands A person serving as starting point for genetic study in a family. Open reading frame ORF is the part of a reading frame that has the potential to be translated Cluster of differentiation The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells in the form of receptor or ligand.
- 18. Polymorphisms Polymorphisms exist whentwo or more different phenotypes exist within different individuals of same population.
- 19.
- 20. Patterns of transmission Whetherdisease alleles are contained in sex chromosomes or autosomes Whether they are dominant or recessive Whether they are fully or partially penetrant
- 21. TYPES OF GENETICDEFECTS Mendelian disorders (single- gene defects) Non-mendelian disorders (multifactorial disorders)
- 22. SIMPLE & MULTIFACTORIALGENETIC TRAITS SIMPLE MENDELIAN TRAITS -Mutations of critical genes alter gene function causing diseased phenotype. -Mutations (<1%)- MENDELIAN GENES Inherited in a predictable pattern-simple mendelian fashion. MULTIFACTORIAL GENETIC TRAITS • Interactive effect of multiple gene products modulated by environmental agents. • Functional polymorphism. • Polymorphisms can be enhanced by environmental agents.
- 24. SYNDROMES ASSOCIATED WITHPERIODONTITISCondition Biochemical/tissue defect Inheritance Periodontal Disease Papillon Lefevre Syndrome Cathepsin C Autosomal recessive AP Halm Munk Syndrome Cathepsin C Autosomal recessive AP Ehlers Danlos Syndrome 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 frucose transporter 1 Autosomal recessive AP Leukocyte adhesion deficiency Type 1 Leukocyte chain adhesion molecule CD18 Autosomal recessive AP, CP
- 25. CTSC gene whichwas observed in 8 families and was found that these mutations resulted in complete loss of enzyme.[Hart et al 1999]. CTSC mutations have also been identified in families with prepubertal periodontitis . It has also been found that polymorphic functional variants of CTSC may be involved in more common type of aggressive periodontitis. Papillon lefevre syndrome
- 26. Epigenetics Used to describethe changes in phenotype or gene expression that result from mechanisms other than changes in underlying DNA sequences.
- 27. Linkage A term usedto describe the tendency for certain genes to be transmitted from parent to offspring because they are located so close to each other. Linkage disequilibrium The occurrence of specific alleles at different locations in the DNA that are relatively close to each other more often than would be expected by chance alone.
- 28.
- 29.
- 30.
- 31. Candidate gene approach Agene mapping approach tests whether one allele of a gene occurs more often in pts than in subjects without disease. Author Study Results Boughman et al 1986 Localized Aggressive periodontitis AgP seggregates with dentinogenesis imperfecta. Localized to long arm of chromosome 4 near the gene for dentinogenesis imperfecta. Tabeta K et al 2009 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
- 32. Case control studies Studiesin which genetic makeup is compared in cases and controls . The populations need to be carefully matched.
- 33. Genome wide analysisstudies(GWAS) GWAS investigates genetic variation across entire genome simultaneously with aim of identifying genetic associations related to a trait or disease of interest. -To identify genetic contributions to common diseases. - Large clinical sample sizes are required to reduce likelihood differences between cases and controls .
- 34. Microarray -Micro array technologiesare capable of assaying >0.5M SNPs Type 2 diabetes >30 genes were discovered
- 35. Familial aggregation study Many diseasesrun in families and the degree of clustering within the family can be estimated by comparing the number of disease cases in relatives of patients to the risk of disease in the general population. 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 volunteers from 75 families (mostly African- Americans)and was mainly females Genotype influences plaque index, but not GI and attachment loss. Mother offspring correlation was stronger than father for both GI and attachment loss.
- 36. Twin studies Comparison oftraits, including diseases in monozygotic, dizygotic or usually both types of twins aimed at determining whether variation in the trait among members of a population is caused by genetic variation in inherited DNA sequences, environmental exposures or combination of both. 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 1967-1999 169 twin pairs: presence of P.ging, A.a, P.intermedia, E.corrodens, F.nucleatum Concordance rate in P.ging-11%, A.a- 22%, P.intermedia- 19%, E.corrodens- 0.34%, F.nucleatum-40%. Michalowicz BS et al 2000 64 MZ, 53 DZ twin pairs: influence of smoking and utilization of dental Chronic periodontitis- 50% heritability independent of smoking
- 37. Seggregation analysis Statisticalanalyses of the patterns of transmission of a disease in relative likelihood that the disease is caused by a single gene with dominant or recessive inheritance, by multiple genes. Author Study Results 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 periodontitis.
- 38. Linkage analysis A techniqueused to map a gene responsible for a trait to a specific location on a chromosome. AUTHOR SUBJECTS FINDINGS Boughman et al., 1988 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 Hart et al., 1993 Fifteen African–American and four Caucasian families (228 individuals) 4q candidate region associated with EOP Li et al., 2004 Four African–American families (28 subjects) LAgP is linked to human chromosome 1q25
- 39.
- 40. IL 1 genepolymorphisms IL 1A …….IL-1α IL1B…...…IL-1β IL1RN…….IL-RA Genes Chromosome 2 This study reports on IL1 composite genotype but no data were presented on carriage rates of individual IL1 R alleles. The following IL1 genetic polymorphisms were studied in relation to periodontitis : IL1A(- 889) IL1 B(+3954) IL1RN VNTR (+2018). Kornmann et al
- 41. Parkhill et al 2000 Overrepresentation of N allele among early onset periodontitis is responsible for over expression of N allele among early onset periodontitis among African American and Caucasian population whereas in Japanese populations carriage of N alleles was found to be low. Found an association between R allele and periodontitis. Three studies have reported carriage rates for IL1B (511) R allele and this genetic polymorphism is not associated with periodontitis. This carriage rate was high among Japanese people (67-78%) than Caucasians(59%). Gore et al 1998, Tai et al 2002, Soga et al 2003 Patients with IL 1 composite genotype more often harbor periodontal pathogens and have increased counts of pathogens. Socransky et al 2000
- 42. Caucasian and non Caucasianstudies Association between IL1 composite genotype and severity of periodontal destruction has also been reported by two cross sectional studies in non Caucasians. McDevitt et al 2000, papanaou et al 2001 other studies have failed to corroborate IL1 as risk factor in periodontitis in Caucasians . Meisel et al 2002,2003 2004 ,Laine et al 2000 Walker et al 2000 Armitage et al 2000 In south American populations the carriage rate of IL1 composite genotype was lower than that reported for Europeans and north American subjects.
- 43. Mcguire and Nunn 1999 Itwas reported among periodontitis patients in maintenance of 5-14 years that IL1 composite genotype increased the risk of tooth loss by 2.7 fold. Mcguire and Nunn 1999 IL1 composite genotype in combination with heavy smoking increased the risk of tooth loss by 7.7 fold . Australian study Culinan et al 2001 A study was done in 295 subjects with gingivitis and moderate periodontitis which were followed for 5 years and IL1 composite genotype was determined and results showed that among non smoking subjects >50 years with IL1 positive had greater probing depths and also was influenced by environmental factors such as age , smoking and the presence of p.gingivalis which suggests IL1 as contributory but non essential risk factor for periodontitis.
- 44. IL 10 polymorphisms IL10 is closely located on chromosome 1, in a cluster with closely related IL genes such as IL19, IL20, IL24. IL10 plays a role in regulation of proinflammatory cytokines such as IL-1 and TNF α Autoantibodies which are produced by stimulation of IL10 and genetic polymorphisms is being found to be detrimental to host tissues and is being found to be linked with periodontitis
- 45. Kinane et al 1999 IL10gene microsatellite markers have been investigated in relation to aggressive periodontitis. Berglund et al 2003 N-allele were more abundant in periodontitis particularly among non smokers in Caucasian populations which lead to production of higher levels of autoantibodies leading to increased periodontal destruction.
- 46. TNF α genepolymorphisms TNFα gene is located on chromosome 6 within MHC gene cluster. Case control studies in Caucasians and non Caucasians have proved TNFα as a putative risk factor for periodontitis. SNP’s in gene coding TNF α are studied mainly in promoter regions (-1031, -863 ,-367, -308, -208, 489)
- 47. Soga et al 2003 AmongJapanese subjects, with periodontitis have been observed for SNPs TNFα in 1031 and -863. Galbraith et al 1998 Association of TNFα polymorphism was found at position -308 among caucasians
- 48. FcϒR polymorphisms They playrole in pathogenesis of periodontitis acting as a bridge between the cellular and humoral branches of immune system. Microorganisms and bacterial antigens are opsonized by a variety of APC’s Leukocyte FcϒR genes are found on chromosomes 1 and encode 3 main receptor classes FcϒR1(CD 64) , FcϒR2(CD 32), FcϒR3(CD16).
- 49. Colombo et al 1998Meisel et al 2001 Studies established that the carriage rates of R allele is relatively high 63-77% in Caucasians and African americans. Loos et al 2003 In Caucasians there was more of N allele expression rather than R allele and that periodontitis patients were homozygous for N allele which lead more periodontal breakdown as compared to those to subjects carrying two R alleles Kobayashi et al 2000 In Japanese patients the FcϒR111b Rallele was associated with generalized EOP and was found more in adult patients with disease reccurence.
- 50. McPherson et al 2007 ANRILis also considered as most important genetic risk factor in myocardial infarction as identified in GWAS on CAD. ANRIL encodes a large antisense non-protein coding RNA molecuele, 126.6 kb full length transcript of 19 differently spliced exons yielding different RNA molecueles of various lengths. ANRIL gene polymorphisms
- 51. Decreased expression ofANRIL is correlated with decreased expression levels of ADIPORI, VAMP3 and C11ORF10. [Bochenek et al 2013] Protein VAMP3 belongs to VAMP/synaptobrevin family and plays a role in phagocytosis wherein VAMP3 mediates the transfer of TNF to cell surface [Murray et al 2005] VAMP3 gene polymorphisms
- 52. Divaris et al 2012 Ina GWAS on periodontal pathogen colonization, a large stretch of VAMP3 region is reported to be strongly associated with increased quantities of pathogenic bacteria. Bochenek et al 2013 Study showed that VAMP3 identified several SNP located at this pathogen specific region to be significantly associated with aggressive periodontitis. Dupuis et al 2010 Franke et al 2010 Borderline associations with aggressive periodontitis were found in C11ORF10 and adjacent genes FADS1 and FADS2. These alleles were identical to previously identified associations with type 2 diabetes, inflammatory bowel disease and crohn’s disease.
- 53. Risk gene ofaggressive periodontitis GLT6D1 mapped to chromosome 9 at 9q34.3 [ Schafer et al 2010]. It encodes for an unknown protein belonging to family of proteins that is characterized by a glycosyl transferase domain 1 . Mainly expressed in gingiva and T cells. GLT6D1 gene polymorphisms
- 54. PGE2 plays animportant role in periodontitis by mediating pro-inflammatory reactions in periodontal tissues and is partly responsible for resorption of alveolar bone . COX 2 is specifically induced by cytokines and specific expression for gingival tissues in periodontitis. Polymorphisms within COX 2 are related to various inflammatory diseases. Ho et al 2008 Xie et al 2009 In Taiwanese and Chinese periodontitis case-control populations, the central portion of COX 2 genetic region was independently shown to be associated with severe periodontitis which was also found true in European population with aggressive periodontitis. COX-2 gene polyorphisms
- 55. Bedoui et al 2003. Binding of NPY to Y1 receptors on a variety of immune cells is thought to be responsible for promoting the anti-inflammatory Th2 response. Lundy et al 2009 NPY is potentially important in the coordination of inflammation and bone metabolism Freitagwolf et al 2014 A second GWAS that systematically analysed gene sex interactions in german cases of aagressive periodontitis and controls observed that a sexually dimorphic role of genetic variants upstream of NPY was associated with aggressive periodontitis. NEUROPEPTIDE Y
- 56. Vitamin D receptorpolymorphisms • Consequences of periodontitis are tooth mobility and eventually tooth exfoliation. • Genetic polymorphisms are being identified in genes coding for mediators for bone homeostasis in VDR gene. VDR gene Bone homeostasis bone mineral density Disorders Osteoporosis, osteoarthritis
- 57. Henning et al 1999 -Studieshave identified a VDR polymorphisms in relation to periodontitis at positons Taq-1, Bsm-1, Fok-1. -The carriage rate of R allele ranges between 12 and 66 % among Brazilians than in Japanese populations. Tachi et al 2003 Association with N allele has been found in Japanese populations.
- 58. Disease modifying genesin implant failures
- 59. Early failures inimplant dentistry Shimpuku et al 2003 Shimpuku et al 2003 Homozygosity if IL1B -511 R-allele has been reported to be associated with marginal bone loss around dental implants in Japanese populations. Santos et al 2004 Carriage of MMP1 -1607 R-allele is associated with early implant loss. BMP plays an important role in bone remodelling and the R allele is of Alu1 polymorphism of the BMP 4 gene associated with marginal bone loss around implants in Japanese patients.
- 60. Late failures inimplant dentistry Rogers et al 2002 laine et al 2006 Studies reported on IL1A -889, IL1B -511, IL1B +3954 and IL1RN VNTR polymorphisms separately in association with late implant failures. Feloutzis et al 2003 -In a study of 90 Caucasian patients were investigated for peri-implant bone loss at time of re-examination [mean 5.6 years] -28 patients carrying IL1 composite genotype were stratified in to non- smokers , former smokers and heavy smokers -Heavy smokers were found to have more annual bone loss. Gruica et al 2004 IL1 composite genotype and smoking were significantly associated with peri-implant bone loss after 8 years in function among Caucasians.
- 61. Evidence for therole of genetics in periodontitis A study was done on 77 siblings of 39 probands with LJP and GJP and it was found that 50 % of siblings suffered from JP. 11 families a co-occurrence of LJP and GJP was present. [Boughman et al 1992]. A family with 527 subjects: 60 with LJP,72 with GJP ,254 unaffected subjects and 141 with unknown periodontal condition in Caucasians and African American families. The authors concluded that the most likely mode of inheritance was autosomal dominant in both American and Caucasian with penetrance of 70% in African americans and 73 % in Caucasians.[Marizata et al 1994] Aggressive periodontitis
- 62. Chronic periodontitis A studywas done in 75 families consisting of 178 subjects to determine familial aggregation .The results showed both gingival index and attachment loss showed a stronger correlation between mothers and offspring compared with fathers and offspring.[Beaty et al 1993] A study analysed periodontal condition in an untreated population in Guatemala consisting of 109 siblings from 40 nuclear families with an age range of 35-60 years. They failed to show familial clustering for periodontal disease.[Dowsett et al 2002] A study was done in 78 subjects and was found that significant sibling relationship effect on plaque, calculus and loss of attachment but not for pocket depth.[van der Velden et al 1993]
- 64. Conclusion In an individualthe development of periodontitis depends on collective presence of a number of environmental risk factors in conjunction with a number of genetic risk factors at a given point during life. However, till date major disease gene mutations have not been identified. A multitude of polymorphisms in genes, most of which code aspects of host immune responses have been explored. In general, the genetic studies in relation to periodontitis are hampered by population heterogenicity and differences in patient selection and diagnostic criteria. Future studies applying candidate gene approach could be guided by results from genome wide searches or by results from gene expression signatures or family linkage analysis to prove a strong association.
- 65. REFERENCES• Textbook ofperiodontology 11th edition by newman takei Carranza chapter : genetic factors associated with periodontitis ;pg 361 • Textbook of periodontology 5th edition by jan lindhe Chapter : susceptibility pg • Textbook of periodontology 6th edition by jan lindhe Chapter host susceptibility pg • Hart, T.C. and Kornman, K.S., 1997. Genetic factors in the pathogenesis of periodontitis. Periodontology 2000, 14(1), pp.202-215. • Michalowicz, B.S., 1994. Genetic and Heritable Risk Factors in Periodontal Disease*. Journal of Periodontology, 65(5s), pp.479-488.
Editor's Notes
- #4 Human genome consists of more than 3 billion pairs of bases arranged in a nucleotide sequence as 23 pairs of chromosomes. Structure of DNA was first described in 1953 by wattson and crick since then genetics have become one of the most exciting and ground breaking sciences.
- #5 Development of a disease is contributed by microbial challenge, genetic factors ,environmental and immune responses which in turn produces a local and systemic effect causing changes in molecular levels leading to development of A DISEASE by producing a local and sysytemic effect.
- #6 Genetics is the centre of biology because gene activity underlies all life processes from cell structure and function to reproduction.TG-deals with transmission of genes from generation to generation, MG-deals with structure and function of genes at molecular level, PG- deals with heredity in groups of individuals wherein the traits are determined by one or more genes, QG- deals with heredity of traits in groups of individuals wherein the traits are determined by many genes simultaneously.
- #7 Mendel is considered as father of genetics who in 1865 gave the principle of inheritnce
- #9 a promoter is a region of DNA that initiates transcription of a particular gene. The coding region of a gene, also known as the coding sequence or CDS (from coding DNA sequence), is that portion of a gene's DNA or RNA, composed of exons, that codes for protein. The region is bounded nearer the 5' end by a start codon and nearer the 3' end with a stop codon. a transcription terminator is a section of nucleic acid sequence that marks the end of a gene or operon in genomic DNA during transcription. su
- #10 A chromosome contains 2 arms p and q joined in centre by a centromere,,,,representation of a chromosome is as follows….
- #11 When there are two identical alleles as AA then it is called homozygous pair and when it has non-identical pair as Aa then it is called as heterozygous pair.
- #15 A phenotype is an individual's observable traits, such as height, eye color, and blood type………The genetic contribution to the phenotype is called the genotype………..
- #20 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 pairsSTR: Simple Tandem repeats.-2,3 or 4 nucleotide repeats on a variable number of locations.
- #21 Genes are passed from parents to children in a predictable manner, and usually segregate in families as predicted by Mendel’s laws.Geneticists can study the pattern of disease transmission in families using a method called segregation analysis. In segregation analysis, the observed pattern of disease in families is compared with patterns expected under various models of inheritance. Geneticists generally apply segregation analyses to determine whether a trait transmission appears to fit a Mendelian or another mode of genetic transmission.The transmission across generations depends on whether the disease alleles lie on autosomes or sex chromosomes, dominant or recessive, fully penetrant or partially penetrant.
- #23 MULTIFACTORIAL GENETIC TRAITS Complex diseases result from interactive effect of multiple gene products modulated by environmental agents.Genes responsible are not altered (mutated) instead they exist in multiple different forms(alleles) which differ in terms of function-functional polymorphism.Polymorphisms can be enhanced by environmental agentsDifficult to estimate the degree of interaction between a range of genotypes & environment.
- #26 Gene mutated in papillon lefevre syndrome is on long arm of chromosome 11. However, the exact mechanism by which an altered function of cathepsin C plays a role in pathogenesis of prepubertal form of periodontitis.it was noted that all cases of prepubertal periodontitis donot have mutations in CTSC. Cathepsin c gene [CTSC]
- #27 This picture shows how normal cells are transferred to cancerous cells by alteration caused by factors other than dna sequences which in turn causes genome instability leading to production of cancerous cells.
- #33 This picture shows a case control study in a population where AA variant is associated with healthy group and CC is associated with diseased group ……in periodontitis cases 59 % of CC variant os seen where as in healthy controls it is 50% of AA variant is seen
- #34 Human genome analysis project was completed in 2003 and development of microarray technologies have made GWAS possible.The observed proportions of offsprings who have the trait or disease being evaluated are compared with proportions that are expected in general populations.
- #35 THRU GWAS MICROARRAY technologies
- #38 Difficulties of approach with this approach relate to the fact that in addition to having many genes in common, family members also share many aspects of a common environment eg diet, nutrition, smoking, infectious organisms and shared socio economic factors…..
- #39 Linkage analysis- these studies are based on the fact that genes that are located close to each other on the chromosome tend to be inherited together as a unit.
- #41 Genes are coded for the respective IL and are located in close proximity with gene clusters on chr 2. Kornman et al first reported association of IL1 genes with periodontitis. Caucasians---white body black hair……
- #45 IL10 SNPs are also found to be associated with systemic lupus erythematosus and rheumatoid arthritis.
- #46 Only limited studies have investigated genetic variations at three positions in IL10 promoter region and further studies have to be confirmed in this aspect.
- #47 +489 coding region in first intron at position +489. Differences in carriage rates of R alleles between Caucasians and other ethnic populations were apparent and for Caucasians varied b/w 20 to 3% while it was 2-3 % for Japanese subjects.
- #48 However more studies are needed to prove the relationship of TNF A with periodontitis.
- #49 An Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system. Its name is derived from its binding specificity for a part of an antibody known as the Fc (Fragment, crystallizable) regionAPC including macrophages, neutrophils etc.CD cluster differntiation.
- #50 To confirm on the study till date no ethnic groups seems promising so further studies has to be carried on to prove the effect of Fcgamma r gene with periodontitis
- #51 Anti sense non-coding RNA in the INK4 locus-ANRIL Best replicated evidence for conferring risk of periodontitis to date has been for gene ANRIL. However the molecular function of ANRIL has remained poorly understood and more studies is needed to proove its relation to periodontitis.
- #52 VESSICLE ASSOCIATED MEMBRANE PROTEIN 3 ……GWAS-genome wide association studies. ADIPORI- adiponectin receptor 1 chromosome 1, VAMP3- vesicle associated membrane protein 3 chromosome 1, C11ORF10- chromosome 11 open reading frame 10 chromosome 11
- #56 Neuropeptide y…NPY has immunomodulatory effects that alter T helper type 1 and T helper type 2 anti-inflammatory balance
- #58 However VDR gene is considered as an interesting candidate gene for periodontitis as it is being found to affect both bone metabolism and immune functions.Further studies should be done to confirm the preliminary data.
- #59 Success of implant dentistry is often reported as survival rate ie implant is functional and present in mouth after a given observation period.
- #60 All patients who lost atleast one implant during the first year appeared to be carriers of R-allele od MMP1 while those who did not lose implants were carriers of R allele of MMP 1 .
- #61 The follow up period of late implant failures in available studies varied from 1-15 years and only genetic variation in genes of IL1 cluster have been investigated.
- #64 this picture shows genetic factors and their association to periodontal disease.Shown in red are candidate genetic factors for which there are current data to support role in periodontitis…shown in yellow are candidate genetic factors for which there are data to support a role for biochemical factors in periodontitis but for which there are no specific data associating with a specific genetic marker with the disease..