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GENETICS AND

HEREDITY


CONTENTSCONTENTSIntroductionIntroductionHistoryHistoryPrinciples of genetics Principles of genetics Molecular basis and biology of Molecular basis and biology of geneticsgeneticsTools for molecular biologyTools for molecular biologyHuman genome projectHuman genome projectModes of inheritanceModes of inheritanceGenetic abnormalitiesGenetic abnormalitiesGenetic risk assessmentGenetic risk assessmentGenetic counselingGenetic counselingBioethicsBioethicsConclusionConclusionReferences References


introductionwww.indiandentalacademy.comwww.indiandentalacademy.com

Genetics:Genetics: The branch of science concerned with The branch of science concerned with

the means and consequences of the means and consequences of transmission and generation of the transmission and generation of the components of biological inheritance .components of biological inheritance .Heredity :Heredity :The transmission of characters from The transmission of characters from parent to offspring by information parent to offspring by information encoded in the parental germ cells .encoded in the parental germ cells .


HISTORYHISTORYGregor MendelGregor Mendel is considered is considered the the ‘Father of genetics’.‘Father of genetics’. He He selected seven contrasting selected seven contrasting character in character in garden peasgarden peas. He . He enunciated the principles of enunciated the principles of heredity :heredity :

1.1.The law of uniformity.The law of uniformity. 2.2.The law of segregation of The law of segregation of

alleles.alleles. 3.3.The law of independent The law of independent

assortment.assortment.



GaltonGalton (1875) initiated (1875) initiated the idea of polygenic the idea of polygenic inheritance.inheritance.GarrodGarrod (1902) (1902) LandsteinerLandsteiner[1900] [1900] discovered ABO blood discovered ABO blood groups.groups.Hardy and WeinbergHardy and Weinberg – – population genetics.population genetics.Watson and crickWatson and crickDiscovered the double Discovered the double helix model of DNAhelix model of DNA



Principles of genetics Principles of genetics Chromosomes and DNA replicationChromosomes and DNA replication1. Organization of DNA into chromosomes .1. Organization of DNA into chromosomes .• Human genomeHuman genome

Principle :Method of things operation.

The ultimate source, origin or cause of something.www.indiandentalacademy.comwww.indiandentalacademy.com

2.Replication of DNA and mitosis2.Replication of DNA and mitosis


3. Assortment and segregation of genes 3. Assortment and segregation of genes during meiosis.during meiosis.


Regulation of gene expression Regulation of gene expression

– TranscriptionTranscription– Post transcriptional modificationsPost transcriptional modifications– m-RNA processingm-RNA processing– TranslationTranslation– Post translational modificationsPost translational modifications


Cloning, nucleic acid hybridization and Cloning, nucleic acid hybridization and DNA sequencingDNA sequencing

• CloningCloning : : creation of a recombinant DNA creation of a recombinant DNA molecule that can be propagated indefinitely.molecule that can be propagated indefinitely.


• Nucleic acid hybridizationNucleic acid hybridization : : It is a It is a fundamental principle in molecular biology that fundamental principle in molecular biology that takes advantage of the fact that the two takes advantage of the fact that the two complementary strands of nucleic acid bind or complementary strands of nucleic acid bind or hybridize to one another with very high hybridize to one another with very high specificity.specificity.

• DNA sequencingDNA sequencing : : A chemical process A chemical process known as dideoxy-sequencing allows the known as dideoxy-sequencing allows the identification of the exact nucleotide sequence identification of the exact nucleotide sequence of a piece of DNA.of a piece of DNA.


MutationsMutations : : A mutation can be defined as any change A mutation can be defined as any change in the primary nucleotide sequence of DNA regardless in the primary nucleotide sequence of DNA regardless of its functional consequences.of its functional consequences.

• Point mutationsPoint mutations : : Involve single nucleotides.Involve single nucleotides.• Transitions Transitions :: Substitutions, if a purine is Substitutions, if a purine is

replaced by another purine.replaced by another purine.• TransversionsTransversions : : Changes from purine to Changes from purine to

pyramidine or vice versa.pyramidine or vice versa.• Missense mutationMissense mutation : : DNA sequence change DNA sequence change

occurs in coding region and alters an amino acid. occurs in coding region and alters an amino acid.


Molecular basis and biology of Molecular basis and biology of geneticsgenetics

DNA structure and function :DNA structure and function :• DNA is made up of deoxyribose-DNA is made up of deoxyribose-

phosphate backbone and a series of phosphate backbone and a series of purine: purine: adenine (A) and guanine (G) adenine (A) and guanine (G) pyrimidine:pyrimidine: thymidine (T) and cystine (C) thymidine (T) and cystine (C) bases of nucleic acid.bases of nucleic acid.


• Complementarity allows the transmission of Complementarity allows the transmission of genetic information from DNAgenetic information from DNA RNA RNA protein. protein.

• It is possible to arrange the 4 bases into 64 It is possible to arrange the 4 bases into 64 different triplet codons (4different triplet codons (433). By arranging the ). By arranging the codons in different combinations and in various codons in different combinations and in various lengths, it is possible to generate the tremendous lengths, it is possible to generate the tremendous diversity of primary protein structure.diversity of primary protein structure.


Nucleoside:Nucleoside: a compound of a sugar with a a compound of a sugar with a purine or pyramidine base by way of an purine or pyramidine base by way of an N glycosyl link.N glycosyl link.

Nucleotide:Nucleotide: a combination of a purine or a combination of a purine or pyramidine, one sugar and a phosphate pyramidine, one sugar and a phosphate group.group.


Genes Genes • A gene is a portion of DNA that contains the A gene is a portion of DNA that contains the

codes for polypeptide sequence.codes for polypeptide sequence.• Genes vary greatly in size : most of them Genes vary greatly in size : most of them

extend over 20-40 kbp.extend over 20-40 kbp.


• ExonsExons : portion of genes that are eventually spliced : portion of genes that are eventually spliced together to form mRNA.together to form mRNA.

• Introns Introns : spacing regions between the exons that : spacing regions between the exons that are spliced out of precursor RNAs during RNA are spliced out of precursor RNAs during RNA processing.processing.


• The regulatory regions in genes most commonly The regulatory regions in genes most commonly involve sequences upstream (5’) of the involve sequences upstream (5’) of the transcription start site. The upstream regulatory transcription start site. The upstream regulatory genes are also referred to as promoters.genes are also referred to as promoters.

• Transcriptional termination signals reside down Transcriptional termination signals reside down stream (3’) of a gene.stream (3’) of a gene.

• 5’ 5’ 3’ 3’Direction of transcription of genetic information Direction of transcription of genetic information

• Key regulatory elements. Eg. globin and Key regulatory elements. Eg. globin and immunoglobin genesimmunoglobin genes


Chromosomes :Chromosomes :Higher eukaryotes have their Higher eukaryotes have their genomic packages –genomic packages –chromosomes, separated from chromosomes, separated from the general cytoplasm by the general cytoplasm by nuclear envelope. nuclear envelope. histones.histones.Heterochromatin :Heterochromatin : These regions These regions tend to be super coiled around tend to be super coiled around histones in condensed regions. histones in condensed regions. Euchromatin :Euchromatin : Most the DNA Most the DNA regions, those coding for regions, those coding for proteins are relatively proteins are relatively uncondensed during interphase uncondensed during interphase and constitute the euchromatin.and constitute the euchromatin.



Transcription and translation•Transcription

•Post transcription modification

•m-RNA processing

•Translation

•Post translation modification

•Stop codons : UAA,UAG,UGA

•Transcriptional controlwww.indiandentalacademy.comwww.indiandentalacademy.com

TranslationTranslation


Tools for molecular biologyTools for molecular biology1) Restriction enzymes :1) Restriction enzymes :Genomic DNA can be cut into a number of Genomic DNA can be cut into a number of fragments by enzymes called restriction fragments by enzymes called restriction enzymes which are obtained from bacteria. enzymes which are obtained from bacteria. Eg. : Enzyme EcoRI.Eg. : Enzyme EcoRI.2) Gel electrophoresis :2) Gel electrophoresis : As DNA is negatively charged molecule, the As DNA is negatively charged molecule, the genomic DNA that has been digested with a genomic DNA that has been digested with a restriction enzyme can be separated restriction enzyme can be separated according to size and charge by according to size and charge by electrophoresing DNA through gel electrophoresing DNA through gel

matrix.matrix.• Pulsed field gel electrophoresis.Pulsed field gel electrophoresis.


3) 3) Southern blotting and DNA probes :Southern blotting and DNA probes :• Southern blotting allows the Southern blotting allows the

visualization of individual DNA fragments.visualization of individual DNA fragments.• DNA probes are useful to indicate where DNA probes are useful to indicate where

the fragment of interest lies.the fragment of interest lies.4) 4) Northern blotting and western Northern blotting and western blottingblotting : :

• Northern blotting is used to visualize Northern blotting is used to visualize RNA fragments on to membrane.RNA fragments on to membrane.

• Western blotting is used to visualize Western blotting is used to visualize proteins.proteins.


Southern blotting

and

DNA probes.


5) Polymerase 5) Polymerase chain reaction : chain reaction :

Minute amounts of Minute amounts of DNA can be DNA can be amplified over a amplified over a million times within a million times within a few hours using this few hours using this invitro techniqueinvitro technique


6) DNA cloning

Recombinant DNA technique, showing incorporation of foreign DNA into plasmid.

Ampicillin resistant genes can be used to distinguish transformed E. coli cells


7) DNA libraries7) DNA libraries These are pools of isolated and cloned DNA These are pools of isolated and cloned DNA sequences that form a permanent resource for sequences that form a permanent resource for further experiments.further experiments.

2 types of libraries :2 types of libraries :– Genomic librariesGenomic libraries -contains almost every -contains almost every

sequence in the genome.sequence in the genome.– cDNA librariescDNA libraries - contain sequences derived - contain sequences derived

from all mRNAs expressed in that tissue.from all mRNAs expressed in that tissue.

8) DNA sequencing :8) DNA sequencing :Used to identify the exact nucleotide sequence Used to identify the exact nucleotide sequence of a piece of DNA.of a piece of DNA.


The human genome project :The human genome project :

The HGP was initiated in the mid The HGP was initiated in the mid 1980’s to characterize the human 1980’s to characterize the human genome, culminating in a genome, culminating in a complete DNA sequence.complete DNA sequence.Main goals of HGP include :Main goals of HGP include :– Creation of genetic mapsCreation of genetic maps– Development of physical mapsDevelopment of physical maps– Determination of the complete Determination of the complete

human DNA sequence.human DNA sequence.Genetic mapGenetic mapPhysical mapPhysical mapHGP was completed in June HGP was completed in June 2000.2000. www.indiandentalacademy.comwww.indiandentalacademy.com

Modes of inheritance :Modes of inheritance :• An inherited trait may depend on a single gene pair An inherited trait may depend on a single gene pair

or on the cumulative effect of a large number of or on the cumulative effect of a large number of genes.genes.

• The former is called The former is called Mendelian or unit factor Mendelian or unit factor inheritanceinheritance. The latter is called . The latter is called polygenic inheritance.polygenic inheritance. Mendelian inheritanceMendelian inheritance

Autosomal inheritanceAutosomal inheritance • Autosomal dominant Autosomal dominant • Autosomal recessiveAutosomal recessive

When the two members of an allelic pair are When the two members of an allelic pair are identical, they are said to be identical, they are said to be homozygoushomozygous and when and when they are unlike each other the combination is said they are unlike each other the combination is said to be to be heterozygous.heterozygous.

• A trait is said to constitute the A trait is said to constitute the phenotypephenotype of an of an individual, while the allelic pair of genes determining individual, while the allelic pair of genes determining the trait constitute the the trait constitute the genotypegenotype for that trait. for that trait.


Sex-linked inheritance :Sex-linked inheritance : Inheritance through the genes carried on sex Inheritance through the genes carried on sex chromosomes X and Y. chromosomes X and Y. X-linked inheritance : X-linked inheritance :

• A male has only one representative of any X-linked A male has only one representative of any X-linked gene a hence is said to be gene a hence is said to be hemizygoushemizygous rather than rather than homozygous or heterozygous. homozygous or heterozygous.

• X-linked recessive : eg. Hemophilia. X-linked recessive : eg. Hemophilia. • X-linked dominant. Eg. Vit. D Resistant rickets, Xg X-linked dominant. Eg. Vit. D Resistant rickets, Xg

blood group. blood group.

Y-linked inheritance :Y-linked inheritance : holandric inheritance (because only in males) holandric inheritance (because only in males)

Eg. Hairy ears. Eg. Hairy ears. Polygenic inheritance (multifactorial)Polygenic inheritance (multifactorial)


GENETIC ABNORMALITIESGENETIC ABNORMALITIESCherubism :Cherubism :

• Occurs as an autosomal dominant disorder Occurs as an autosomal dominant disorder and with 100% penetrance in males and 50 and with 100% penetrance in males and 50 to 75% penetrance in females, with 2:1 male to 75% penetrance in females, with 2:1 male predominance.predominance.

• Marked fullness of the jaws.Marked fullness of the jaws.


•Ectopic eruption, severe malocclusion.Ectopic eruption, severe malocclusion.

•Permanent teeth may be missing or Permanent teeth may be missing or malformed as the developing tooth follicles are malformed as the developing tooth follicles are displaced.displaced.


Osteogenesis imperfecta :Osteogenesis imperfecta :• Caused by mutations that cause a quantitative Caused by mutations that cause a quantitative

defect in production of type I collagen. defect in production of type I collagen. • OI is the probably the most common inherited OI is the probably the most common inherited

bone disease.bone disease. OI type I : autosomal dominant, most common.OI type I : autosomal dominant, most common. OI type II : autosomal recessive, most severe.OI type II : autosomal recessive, most severe. OI type III : both AD and AR.OI type III : both AD and AR. OI type IV : AD.OI type IV : AD.• Classically this condition includes fragile Classically this condition includes fragile

bones, blue sclerae, ligamentous laxity, hearing bones, blue sclerae, ligamentous laxity, hearing loss and dentinogenesis imperfecta.loss and dentinogenesis imperfecta.


• Primary teeth are more severely affected than Primary teeth are more severely affected than the permanent teeth.the permanent teeth.

• Crowns are described as shortened and bell Crowns are described as shortened and bell shaped with cervical constriction.shaped with cervical constriction.


Cleidocranial dysplasia :Cleidocranial dysplasia :

• Inherited as AD with high penetrance with wide Inherited as AD with high penetrance with wide variability in expression. variability in expression.

• A gene for this disorder has A gene for this disorder has

been mapped to been mapped to

chromosome 6p21.chromosome 6p21.


• Maxillary hypoplasia gives the mandible a Maxillary hypoplasia gives the mandible a relatively prognathic appearance.relatively prognathic appearance.

• Palate is narrow and high arched.Palate is narrow and high arched.• Increased incidence of submucosal clefts and Increased incidence of submucosal clefts and

complete or partial clefts of the palate involving the complete or partial clefts of the palate involving the hard and soft tissues.hard and soft tissues.

• Non union of symphysis of mandible.Non union of symphysis of mandible.• Unerupted supernumerary teeth.Unerupted supernumerary teeth.


Crouzon’s syndrome Crouzon’s syndrome (Craniofacial dysostosis) :(Craniofacial dysostosis) :

• AD with complete penetrance and variable AD with complete penetrance and variable expressivity.expressivity.

• Mutation in the fibroblast growth factor receptor Mutation in the fibroblast growth factor receptor 2 gene (FGFR2) which maps to chromosome 2 gene (FGFR2) which maps to chromosome 10q25-q26, cause this syndrome.10q25-q26, cause this syndrome.

• Shallow orbits are the most common feature.Shallow orbits are the most common feature.• Frog like facies. Midface hypoplasia and Frog like facies. Midface hypoplasia and

exopthalmos are striking.exopthalmos are striking.www.indiandentalacademy.comwww.indiandentalacademy.com

• Mandibular prognathism with nose resembling Mandibular prognathism with nose resembling parrot’s beak.parrot’s beak.

• Maxillary hypoplasia, high arched palate.Maxillary hypoplasia, high arched palate.• Bilateral posterior lingual cross bites.Bilateral posterior lingual cross bites.• Anterior open bite.Anterior open bite.


Treacher Collins syndrome Treacher Collins syndrome (mandibulofacial dysostosis) :(mandibulofacial dysostosis) :

• AD with high degree of penetrance but variable AD with high degree of penetrance but variable expressivity.expressivity.

• Mutation in a gene of unknown function referred to as Mutation in a gene of unknown function referred to as treacle which maps for 5q 32 – 33.1 are responsible.treacle which maps for 5q 32 – 33.1 are responsible.

• Facial appearance is characteristic and is often Facial appearance is characteristic and is often described as bird like or fish like.described as bird like or fish like.


• Includes various degrees of hypoplasia of the Includes various degrees of hypoplasia of the mandible, maxilla, zygomatic process of mandible, maxilla, zygomatic process of temporal bone, external and middle ear.temporal bone, external and middle ear.

• Oral finding include cleft palate, macrostomia, Oral finding include cleft palate, macrostomia, high arched palate, dental malocclusion high arched palate, dental malocclusion consisting of apertognathia and widely consisting of apertognathia and widely separated and displaced teeth.separated and displaced teeth.

• The peculiar broad and concave nature of the The peculiar broad and concave nature of the inferior border of the mandible is characteristic.inferior border of the mandible is characteristic.


Pierre Robin syndrome :Pierre Robin syndrome : • Fetal malposition and interposition of the tongue between the palatal shelves is probable Fetal malposition and interposition of the tongue between the palatal shelves is probable

etiology.etiology.

• Severe micrognathia and mandibular hypoplasia.Severe micrognathia and mandibular hypoplasia.

• U shaped cleft palate is common.U shaped cleft palate is common.

• Glossoptosis Glossoptosis

• High arched palate sometimes.High arched palate sometimes.


Down syndrome Down syndrome (Trisomy 21)(Trisomy 21) ::

• Incidence – 1 in 600-700.Incidence – 1 in 600-700.• Most cases of trisomy 21 are caused by non Most cases of trisomy 21 are caused by non

disjunction, resulting in an extra chromosome.disjunction, resulting in an extra chromosome.• Skull is brachycephalic with flat occiput and Skull is brachycephalic with flat occiput and

prominent forehead.prominent forehead.• Frontal, sphenoid sinuses absent and maxillary Frontal, sphenoid sinuses absent and maxillary

sinus is hypoplastic.sinus is hypoplastic.www.indiandentalacademy.comwww.indiandentalacademy.com

• Fissured tongue, Macroglossia.Fissured tongue, Macroglossia.• Open mouth postureOpen mouth posture• Palatal width and length are significantly Palatal width and length are significantly

decreased, bifid uvula, cleft lip and palate.decreased, bifid uvula, cleft lip and palate.• Delayed eruptions, hypodontia, microdontia, Delayed eruptions, hypodontia, microdontia,

crown root malformations.crown root malformations.• Occlusal disharmonies, posterior crossbites, Occlusal disharmonies, posterior crossbites,

apertognathia, severe anterior teeth crowding.apertognathia, severe anterior teeth crowding.


Hemifacial atrophy :Hemifacial atrophy :• Progressive unilateral atrophy of the face.Progressive unilateral atrophy of the face.• Tongue, lips and salivary glands may show Tongue, lips and salivary glands may show

hemiatrophy.hemiatrophy.• Developing teeth may show incomplete root Developing teeth may show incomplete root

development and delayed eruption.development and delayed eruption.


http://www.ispub.com/xml/journals/ijds/vol1n1/hemifacial-fig3.jpg

Cleft lip and palate :Cleft lip and palate :• Majority of cases of cleft lip or cleft palate or both can be explained Majority of cases of cleft lip or cleft palate or both can be explained

by the multifactorial threshold hypothesis (polygenic inheritance).by the multifactorial threshold hypothesis (polygenic inheritance).• Abnormalities of tooth number, size, morphology, calcification and Abnormalities of tooth number, size, morphology, calcification and

eruption.eruption.• Prevalence of hypodontia increase with severity.Prevalence of hypodontia increase with severity.• Tooth formation often delayed and enamel hypoplasia, microdontia Tooth formation often delayed and enamel hypoplasia, microdontia

or macrodontia and fused teeth are seen frequently.or macrodontia and fused teeth are seen frequently.


Macroglossia :Macroglossia :

Down syndromeDown syndrome

Hunter syndromeHunter syndrome

Hurler syndromeHurler syndrome

Maroteaux lamy Maroteaux lamy

syndromesyndrome


Microglossia :Microglossia :

Oromandibular – Oromandibular –

limb hypogenesis limb hypogenesis

spectrum.spectrum.

Moebius Moebius

sequence.sequence.

Freeman Sheldon Freeman Sheldon

syndrome syndrome


Amelogenesis imperfecta :Amelogenesis imperfecta :• AI represents a group of hereditary defects of enamel AI represents a group of hereditary defects of enamel

unassociated with any other generalized defects.unassociated with any other generalized defects.• Types :Types :

• Hypoplastic – mainly AD.Hypoplastic – mainly AD.• Hypocalcified – AD & AR.Hypocalcified – AD & AR.• Hypomaturation – AD & AR.Hypomaturation – AD & AR.


Dentinogenesis imperfecta :Dentinogenesis imperfecta :• The association between The association between

DI and OI is well DI and OI is well recognized although each recognized although each condition may occur condition may occur independently independently

• Type IType I – AD generally. – AD generally. Both DI and OI presentBoth DI and OI present

• Type IIType II – Never occurs – Never occurs with OI. Autosomal with OI. Autosomal dominant.dominant.

• Type IIIType III – Brandywine – Brandywine type. Same clinical type. Same clinical appearance of teeth as appearance of teeth as types 1 and 2 but it may types 1 and 2 but it may also show multiple pulp also show multiple pulp exposures in deciduous exposures in deciduous teeth.teeth.


Genetic risk assessment :Genetic risk assessment :• One of the most important aspects of genetic One of the most important aspects of genetic

counseling is the provision of a risk figure.counseling is the provision of a risk figure.

Probability / probability of recurrence (P) :Probability / probability of recurrence (P) : Probability of an outcome can be defined as Probability of an outcome can be defined as

the number or more correctly, the proportion of the number or more correctly, the proportion of times it occurs in a large series of events.times it occurs in a large series of events.

Probability is indicated as a proportion of 1. Probability is indicated as a proportion of 1.

Probability theory :Probability theory :• Laws of addition and multiplication Laws of addition and multiplication


Baye’s theorem : Baye’s theorem :

It provides a very valuable method It provides a very valuable method for determining the overall probability for determining the overall probability of an event or outcome, such as carrier of an event or outcome, such as carrier status by considering all initial status by considering all initial possibilities, eg. carrier or non carrier possibilities, eg. carrier or non carrier and then modifying or conditioning and then modifying or conditioning these by incorporating information. these by incorporating information.


•Anterior informationAnterior information

•Prior probability Prior probability

•Posterior Posterior informationinformation

•Conditional Conditional probabilityprobability

•Joint probability Joint probability

•Relative Relative probabilityprobability


Risks in multifactorial disorders :Risks in multifactorial disorders :

• One of the basic principles in the One of the basic principles in the multifactorial inheritance is that the risk of multifactorial inheritance is that the risk of recurrence in first degree relatives, siblings and recurrence in first degree relatives, siblings and offspring, equals the square root of incidence of offspring, equals the square root of incidence of the disease in the general population i.e. the disease in the general population i.e. P P 1/21/2

where P equals the general population where P equals the general population incidence.incidence.

• The theoretical risks for 2nd and 3rd The theoretical risks for 2nd and 3rd degree relatives can be shown to approximate degree relatives can be shown to approximate to to P P 3/43/4 and and P P 7/87/8 respectively. respectively.


Genetic counseling:Genetic counseling:• Patients with a great variety of diseases Patients with a great variety of diseases

and syndromes are now referred for and syndromes are now referred for evaluation and counseling. evaluation and counseling.

• Genetic evaluation and counseling has Genetic evaluation and counseling has become team affair.become team affair.

• The traditional role of counselor is to The traditional role of counselor is to estimate P, the probability of recurrence.estimate P, the probability of recurrence.

• Family physician is the most appropriate Family physician is the most appropriate person to do the counseling because he person to do the counseling because he know the family, its attitudes and know the family, its attitudes and socioeconomic background better than a socioeconomic background better than a consultant.consultant. www.indiandentalacademy.comwww.indiandentalacademy.com

Evaluation of the patient :Evaluation of the patient :

• The genetic evaluation of the family begins well before the The genetic evaluation of the family begins well before the genetic counseling process.genetic counseling process.

Does the patient have a disease of clearly non genetic Does the patient have a disease of clearly non genetic origin, such as infection or birth trauma ?origin, such as infection or birth trauma ?

Does the baby have a disease of clear genetic etiology, Does the baby have a disease of clear genetic etiology, such as haemophilia ?such as haemophilia ?

If the patient’s disorder doesn't fall into either of the above If the patient’s disorder doesn't fall into either of the above categories, does the patient have features that suggest a categories, does the patient have features that suggest a syndrome ?syndrome ?

When a syndrome cannot be identified, one must consider When a syndrome cannot be identified, one must consider what further investigations are necessary. Is examination what further investigations are necessary. Is examination of the chromosomes indicated ?of the chromosomes indicated ?

• In any case, the family history should be screened for In any case, the family history should be screened for clues to the possible genetic basis for baby’s problem.clues to the possible genetic basis for baby’s problem.


Genetic counseling – Aims :Genetic counseling – Aims :

Obtaining a full and careful history.Obtaining a full and careful history. Establishing an accurate diagnosis.Establishing an accurate diagnosis. Drawing a family free is essential.Drawing a family free is essential. Estimating the risk of a future Estimating the risk of a future

pregnancy being affected of carrying a pregnancy being affected of carrying a disorder.disorder.

Information givingInformation giving Continued support and follow up.Continued support and follow up. Genetic screening – includes prenatal Genetic screening – includes prenatal

diagnosis, carrier detection.diagnosis, carrier detection.www.indiandentalacademy.comwww.indiandentalacademy.com

Bioethics in geneticsBioethics in genetics

• In no other area of biomedical research there In no other area of biomedical research there has been a greater concern for ethical issues has been a greater concern for ethical issues than in the field of human genetics.than in the field of human genetics.

• Serious issues related to the participation of Serious issues related to the participation of human subjects in genetic research are raised human subjects in genetic research are raised particularly when the intervention involves particularly when the intervention involves rights of human embryo and subjects who are rights of human embryo and subjects who are not competent to give informed consent.not competent to give informed consent.

• Recent experiments on cloning sheep and Recent experiments on cloning sheep and mice have brought human cloning into the mice have brought human cloning into the realm of possibility, raising additional set of realm of possibility, raising additional set of ethical legal and social issues.ethical legal and social issues.www.indiandentalacademy.comwww.indiandentalacademy.com

General guidelines :General guidelines :

• Clinical research besides being subject to general ethical Clinical research besides being subject to general ethical considerations of protection from harm and voluntaries of considerations of protection from harm and voluntaries of participation has following addition considerations: participation has following addition considerations:

The harm may not only be physical but also psychosocial.The harm may not only be physical but also psychosocial. Maintaining confidentially of research findings.Maintaining confidentially of research findings. Genetic counseling is akin to therapy. Written explanation Genetic counseling is akin to therapy. Written explanation

about presentation and natural courses of disease, about presentation and natural courses of disease, interventions, etc has special place in clinical research.interventions, etc has special place in clinical research.

Genetic manipulations have consequences for future, some Genetic manipulations have consequences for future, some of which are unknown. Hence, greater care towards potential of which are unknown. Hence, greater care towards potential dangers is necessary.dangers is necessary.

Institutional ethical committee.Institutional ethical committee. Prenatal diagnostic techniques act 1994.Prenatal diagnostic techniques act 1994.


Ethical issues :Ethical issues :• Pedigree studies Pedigree studies • Genetic screening :Genetic screening : Screened subjects are entitled to receive information in a Screened subjects are entitled to receive information in a

way that :way that :They can understand what is proposed to be done.They can understand what is proposed to be done.They must be made aware of any substantial risk.They must be made aware of any substantial risk.They must be given time to decide whether or not They must be given time to decide whether or not

they would like to participate or not. they would like to participate or not. • Therapeutic trials including gene therapy :Therapeutic trials including gene therapy :

Recombinant protein productsRecombinant protein productsGene therapy Gene therapy

Somatic cell gene therapySomatic cell gene therapy Germ line therapyGerm line therapy


Gene therapy for enhancing characters.Gene therapy for enhancing characters. Eugenic genetic engineering.Eugenic genetic engineering.• DNA banking DNA banking • DNA diagnosis DNA diagnosis

Pre morbid diagnosis in children.Pre morbid diagnosis in children. Pre morbid diagnosis in adults.Pre morbid diagnosis in adults. DNA diagnosis in forensics.DNA diagnosis in forensics.

• Prenatal diagnosisPrenatal diagnosis• Assisted reproductive techniques Assisted reproductive techniques

Cloning : Since its safety, success, Cloning : Since its safety, success, utility and ethical acceptability is not utility and ethical acceptability is not yet established, research on cloning yet established, research on cloning with intent to produce an identical with intent to produce an identical human being as of today is prohibited. human being as of today is prohibited.





REFERENCES :Emery’s elements of medical genetics.

– Robert F. Mueller, Ian D. Young.– 11th edition.

Kumar and Clark – Clinical medicine. – Praveen Kumar– Michael Clark– 5th edition.

Harrison’s – Principles of internal medicine.

– Volume 1, 5th edition.Medical genetics

- Jorde, Carey- 5th edition

Essentials of Human genetics-Bhatnagar, Kothari, Mehta


Text book of oral pathologyText book of oral pathology - Shafer- Shafer - 4- 4thth edition edition

Indian council of medical research.Indian council of medical research.API textbook of medicine.API textbook of medicine.– Siddharth N. ShahSiddharth N. Shah– 7th edition.7th edition.Smith’s – Recognizable patterns of Smith’s – Recognizable patterns of human malformation.human malformation.– Kenneth Lyons Jones.Kenneth Lyons Jones.– 5th edition.5th edition.

Oral pathology – Regezi and Sciubba. - Clinical pathologic correlations. - 3rd edition.


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