GENETICS INDIAN DENTAL ACADEMY
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Introduction
William Bateson defines Genetics as “Branch of biology that deals with the study of heredity and the variations in organisms” www.indiandentalacademy.com
Heredity ď Ž
The transmission of characters from parents to offspring is Heredity. The differences observed are variations.
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An Individual may inherit the characteristics from male parent or the female parent or may exhibit characteristics of both
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Example: Color of eyes from mother and skin from his/her father. Certain disease like Hemophilia and epilepsy has observed to pass from one generation to another.
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Cytology
The term cell was first coined by Robert Hook in 1665. All living organisms from bacteria to the tree, Amoeba to man has a common unit of structure – The Cell.
Cell can be defined as “Basic structure and functional unit of an organism” www.indiandentalacademy.com
Cell Structure ď Ž
It is made up of different organelle that is the cellular cytoplasm, Endoplasmic Reticulum's, Ribosome's, Mitochondria, Nucleus etc.
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Cell Membrane or Cytoplasmic Membrane : ď Ž
Cells are bound by distinctive membrane called the Cytoplasmic Membrane.
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• Composed of phospholipids and proteins in the ratio of 3:2 • Synthesized by granular Endoplasmic Reticulum in collaboration with golgi complex
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Functions: ď Ž
Form boundaries which selectively limit diffusion actively control the passage of Electrolytes and small organic molecules.
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Generate Bioelectric potential and they act on surface for attachment of enzymes and other metabolic systems. www.indiandentalacademy.com
Endoplasmic Reticulum: 2 types Smooth or A granular Rough or Granular
The rough appearance is due to the presence of Ribosome's attached to it The smooth appearance lacks the presence of Ribosome's www.indiandentalacademy.com
Functions:
Granular – Protein syntheses by means of attached ribosomes and synthesize some Carbohydrates.
A Granular – Synthesizes Carbohydrates, respiration, detoxification of lipids, cholesterol etc.
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Ribosome: Contains Ribo nuclear protein particles. There are small bodies composed of protein and RNA which are responsible for synthesis of proteins from Amino acids.
Mitochondria: There are membrane bound Organelle with outer membrane and inner membrane, Also called Power house of a cell.
Functions: 1. The enzyme found within help in aerobic respiration. 2. Helps in release of energy (ATP Synthesis) www.indiandentalacademy.com
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Golgi Complex: Also known as Golgi Apparatus. It is flattened tubes or sack placed one above the other in a pile or stack.
Functions: ď Ž Secretion a packaging of certain substance of cell. www.indiandentalacademy.com
Nucleus: - Lies in the centre of the cell Spherical in Shape Composed of Nuclear envelope, Nucleoplasm, Chromatin and Nucleolus.
Functions: Helps in building DNA and other important molecules of cell. Helps in carrying Genes that determine hereditary characteristics. Helps in the production of Ribosome’s. www.indiandentalacademy.com
Structure of Chromosome Chromatids: Two cylindrical rod shaped structure placed opposite to each other. They are held together at Centromere. ď Ž
Primary Constriction: It is a region which attaches the two Chromatids. Also known as Centromere.
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Kinetocore: It is associated with centromere which helps in attachment of spindle fibres during cell division. www.indiandentalacademy.com
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Telomere: - It is the end point of Chromosome.
Prevents the adhesive of one chromosome to another.
Help in replication of chromosome. www.indiandentalacademy.com
Chromatin Fibre: Thread like structure composing Chromosome. Functions: - Are often described as Vehicles of Heredity. They carry Heredity information from one generation to next in the form of DNA. Sex chromosome determines Sex. Helps in growth, cell division, cell differenciation
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Structure of DNA: The structure of DNA was discovered by Watson and Crick in 1953. DNA in a chromosome is in a form of very fine firbres. Each fibre consists of 2 strand which are parallel to each other but running in anti parallel direction.
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Each strand is coiled in the form of right handed Spiral or Helix and the 2 strands are coiled with each other to form a double Helix. Each strands of DNA fibres consists of a backbone and a base. The phosphate of one Nucleotid is linked to the sugar of next nucleotide. Both the opposite strands are linked by purine and pyramidine bondings. This purine and pyramidine is known as Complimentary Base Pairing. Bonding is always specific between the 2 opposite strand adenine with thymine and cytosine always with Guainine .
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The order in which these 4 bases are rearranged along the length of the strand determines the nature of proteins that cant be synthesized under its influence. www.indiandentalacademy.com
Duplication of the Chromosomes:
Chromosome has remarkable property of duplication. Duplication of Chromosome involves Duplication of DNA.
The two strands of DNA molecule to be duplicated unwind and separate from each other so that their base is free.
A new strand is now synthesized opposite each original strand of DNA in such a way that Adnine is formed opposite thymine,guanine is formed opposite cytosine. This new strand is now synthesized opposite each original strand of DNA to form a new molecule. www.indiandentalacademy.com
Ribo Nuclic Acid: ď Ž Found in the Mitochondria and Chloroplast of the cells. RNA contains sugar Ribose instead of deoxyribose. ď Ž
Instead of base, thymine contains Uracil. It is present in different forms. mRNA transfer RNA and ribosomal RNA. www.indiandentalacademy.com
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Mendelian Genetics: Gregor Mendel is known as Father of Genetics. Gregor Mendel explained the basic principles of heredity by carrying his experiments on the common peas.
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Experiment of Mendel: Mendel selected stem height as a trait to be studied. He made crosses between tall and dwarf plants. The plant with which he started his experiment formed the parental generation. www.indiandentalacademy.com
alltall
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Mendel observed that all the offspring resulting from this cross were tall. These tall offspring were called Hybrids. This was taken as F1 or first generation. Next, F1 was allowed to self fertilized. The plant taken out of this selfing was F2. F2 included both tall and dwarf. They were no plant of intermediate height. The appearance of dwarfness in F2 was of great importance because characters had temporarily disappeared in F1. When Mendel counted actual number of plant of the F2 he found, out of 1064 787 were tall and 277 dwarf. 75% tall 25% dwarf in the ratio 3:1. Mandel observed only one of the two contrasting characters appeared in F1 that is tallness, other character dwarfness was suppressed. Characters appeared in F1 is Dominant and suppressed one is Recessive. www.indiandentalacademy.com
Mendel’s Principle of Dominance and Recessive: It states that “One factor in a pair may prevent the expression of the other factor.” In other words the expression of the dominant character and suppression of the recessive character in F1 hybrids is the principle of dominance. www.indiandentalacademy.com
Law of Segregation: It states that “Whenever a pair of factors for a character is brought together in hybrid the factor segregate or separate during the formation of gamets.” Hence each gamet receives a single ‘pure’ factor either dominant or recessive. www.indiandentalacademy.com
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Explanation of Law of Segregation: Mendel used T for dominant and t for recessive. According to Mendel pure breeding tall plant of parental generation
contained
2
identical
factor
tallness TT, 2 identical factor for dwarfness tt.
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for
During the formation of Gamets the factors separate. All Gamets of tall plant carry T. All Gamets small plant carry t. The zygotes produced by these Gamets will have factors Tt. Hence all the offspring will be Tt. All factors Tt will segregate. This means 50% of the total number of Gamet is T and the remaining 50% is t. When Gamet carrying these factors fuse to form zygotes, there will be 3 combination, TT,tt and Tt. TT and Tt produce small plants, tt form dwarf plant. Thus a total of ¾ tall and ¼ dwarf. This is the 3:1 ratio observed by Mendel. www.indiandentalacademy.com
Terminologies: Genotype:
The Genetic constitution of an individual.
Phenotype:
The manifested character of an individual.
Expressivity:
It is measure of the degree of the manifestation of Phenotypic characteristics of symptoms. The expressivity of the Gene may be high, low or variable.
Alleles:
Alternate form of Genes which exist are called Alleles. www.indiandentalacademy.com
Homozygous: When both the alleles are identical in the locus of a pair of chromosome it is called Homozygous.
Heterozygous: When both the alleles are not identical in the locus of pair of chromosome it is called Heterozygous.
Recessive Gene: It is a Gene which fails to express itself in the presence of its contrasting dominant Gene, in a Heterozygote.
Dominant Gene: The Gene which expresses itself in the presence of its contrasting dominant Gene, in a Heterozygote. www.indiandentalacademy.com
CELL DIVISION ď Ž
Cell Division or Cell Reproduction is a process by which new cells arise by division of existing cells. Cell division consists of 2 separate process. Karyokinesis and Cytokinesis.
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Karyokinesis: Division of the Nucleus. Cytokinesis: Division of the Cytoplasm.
There are 2 types of Cell Divisions: Mitosis or indirect cell division. Meiosis or reduction division.
Mitosis: It is the cell division in which replication of chromosome are distributed to daughter cells in such a way that they come to have exactly the same number of chromosomes as the www.indiandentalacademy.com parent cell.
Stage of Mitosis: 1.Prophase 2.Metaphase 3.Anaphase 4.Telaphase. ď Ž Prophase: In this phase the long thin thread like chromosomes are coiled or folded to become thick and short. This process is called Condensation. Each chromosome is a double structure composed of two threads or chromotids. They are held together in a region called Centomere. www.indiandentalacademy.com
The Centriole too are duplicated just before prophase starts. There are two pairs. One pair begins to move away towards to the other pole of the cell. Delicate fibrils appear around each pair and each looks like a star called Aster. Some fibrils enter from one aster to other and are called Spindle.
The nuclear envelope breaks down and disappears and the spindle moves to the central position of the cell.
The nucleus shrinks and disappears. Chromosome is distributed on the spindle. www.indiandentalacademy.com
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Metaphase: Some spindle fibre gets attached to centriole of Chromosome. They bring the chromosome to equator of the spindle (congression). www.indiandentalacademy.com
Anaphase:
In
this
phase
the
two
Chromotids of each chromosome separate and
are
now
called
‘Daughter
Chromosomes’. Soon after this separation, one daughter chromosome moves to one pole and the other moves to the opposite pole.
The
centrometer
of
each
chromosome leads this movement and the arms,trail behind it. www.indiandentalacademy.com
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Telophase: The daughter chromosome arrive at the poles. Soon they start uncoiling or decondensing and become thin and long once again. - The spindle breaks down and the spindle fibres disapprove. - The new nuclear envelope is formed around each group of chromosome. The nucleolus reappears. www.indiandentalacademy.com
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Meiosis: It is defined as “All division occurring in diploid cells, in which the daughter cells receive only one haploid number of chromosomes. Meiosis I (heterotypic Division;
Prophase I
Leptotene
Metaphase I
Zygotene
Anaphase I
Pachytene
Telophase I
Diplotene
Meiosis
Diakinesis Meiosis II (homotypic Division;
Prophase II Metaphase II Anaphase II Telophase II
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Prophase I: Structured under 4 stages.
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Leptotene: The chromosomes are thin and long. The chromosomes appear as strings of beads, the beads are chromomeres. www.indiandentalacademy.com
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Zygotene: The members of each pair of homologous chromosomes (maternal and paternal) come to lie side by side, closely applied at energy point from one end to another. This process of pairing is called synapses
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Each pair unit is called bivalent. Since each period chromosome consists of two chromatids, a bivalent has four chromatids. Hence each unit may also be called Tetrad. www.indiandentalacademy.com
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Pachytene: It is long lasting stage, in
which
two
non
sister
chromatids of each tetrad get coiled around each other and exchange segments. The process is called Genetic crossing over. ď Ž
The points where such exchanges have occurred appear X- shaped and are called Chiasmata. www.indiandentalacademy.com
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Diplotene: This is a stage in which maximum condensation of chromosome occurs and they appear thicker and shorter than any other stage.
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The force of attraction that brought the homologous chromosomes together at zygotene, has disappeared. There is repulsion between the member of a pair because of repulsion. Chiasmata are shifted towards the end of the bivalents and is called terminalization.
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Diakenesis: The chromosomes have condensed to their maximum. Each bivalent clearly shows four chromatids. The ring like or loop like appearance is still there. It is indication that terminalization is complete.
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The nuclear envelope and nucleus disintegrate and the chromosomes are released into the cytoplasm to establish contact with spindle fibres. www.indiandentalacademy.com
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Metaphase I: This is same as that of Mitosis except that the bodies attaching the spindle, microtubles are bivalent and not single
chromosome.
Bivalent
pair directed towards apposite pole.
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Anaphase: During this stage each recombined chromosome with two chromatids move to its irrespective poles as it gets separated from its partner. The chromatids of each chromosome do not separate at this stage as in mitosis. Here the whole chromosome are separated at Anaphase I and not chromatids because of its reduction to half the chromosome occurs. www.indiandentalacademy.com
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Telophase: Chromosome
reaching the
poles
New
become
uncoiled.
nuclear
envelop appears around them and a new Nucleus. Each new nucleus is haploid (n) and contains only half the number of chromosomes
found
in
the
original
nucleus. Hence M1 is called Heterotypic division. www.indiandentalacademy.com
GENETIC DISORDERS Genetic Disorders can be categorized into 5 major groups according to the etiology
Single Gene disorder
Chromosomal disorder
Multifactorial disorder
Disorders caused by teratogens
Disorders of unknown etiology www.indiandentalacademy.com
Single Gene Disorders: A single mutant gene causes them. A mutant gene is an altered gene that can cause abnormal characteristics and is transmitted from one generation to another. If the mutant Gene present in autosome its called Autosomal sex chromosome or X-linked or sex linked. If mutant Gene causes an abnormal trait in a single dose it is Dominant Gene. If mutant Gene causes an abnormal trait in double dose it Recessive Gene. Hence single Genetic Disorders follow one of the 4 following pattern of inheritance. www.indiandentalacademy.com
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Autosomal Dominant Disorder: Here the mutant Gene is located on one chromosome of the autosomal pair and the comparable Gene or partner chromosome is normal. Example: Achondroplasia.
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Autosomal Recessive Disorder: Common in consanguineous marriage between close relative. Both father and mother have Single Mutant Gene, but they are normal phenotypically. But in the children, the mutant Gene will be present in both the chromosomes of the homologus pair and the abnormal trait expresses phenotypically.
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Example: Sickle cell anemia, cystic fibrosis www.indiandentalacademy.com
X-Linked Dominant Disorder: The Dominant Mutant Gene expresses itself in a single dose and hence both females and males are effected.
Example: Hypo Phosptaemia.
X-Linked Recessive: Here the Recessive Mutant Gene is present on the X-Chromosome of males and females, but only males are effected. This is because the genotype of female sex chromosome is XX and so the normal X mask the effect of the Mutant Gene on the X-Chromosome. So the females become the carriers.
Whereas the male Genotype of the sex chromosome is XY and Y chromosome do not carry any Genes except h-7 Anti Gene. Hence the Recessive Mutant Gene on the X chromosome expresses itself and the male become affected.
Example: Hemophilia, Color blindness.
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Chromosomal Disorders: Occur due to Chromosomal aberrations.
Normal chromosomal complement in Male
- 46xy
Female - 46xx
Any deviation either in number or structure of the chromosomes is refereed to as Chromosomal Aberrations. www.indiandentalacademy.com
Alteration in number:
Monoploidy: Cells contain only a hoploid number of Chromosomes.
Polyploidy: Cells contain Chromosomes in the multiples of the haploid number. Example: 3n=69 Chromosomes, 4n=92 Chromosomes.
Anueploidy: Cells contain Chromosomes in any number which is not exactly the multiple of haploid number. Example: 2n+/-1 www.indiandentalacademy.com
The Abnormalities In The Pattern Of Chromosomal Structure: Translocation: In this there is a attachment of one piece of chromosome to other. Invertion: The breaking of a chromosome in two places and subsequently rejoining with the middle part inverted. Deletions: The absence of piece of chromosomes. Insertion: When a chromosomal segments are removed from its normal position and inserted in a different position. www.indiandentalacademy.com
Multifactorial Disorder: Among the Genetic disorders, the multifactoral inherited group occurs most frequently in general population and probably accounts for the most commonly occurring conditions in the maxillofacial deformities.
Example: Cleft palate and Cleft lip
These disorders are also called Polygene as they are the consequences of additive effects of multiple genes of minor importance. None of these genes can be responsible by itself for the abnormality. They are called multifactorial because of the presence of combined effects of genetic and environmental factors. www.indiandentalacademy.com
Disorders Caused By Teratogens: A group of malformations are caused by maternal exposure of Teratogenic agents during pregnancy.
The Teratogenes could be:
Drugs. Example: Thalidomide, Anticonvulsant, Antimalarial.
Infection. Example: Rubella
Ionising Radiation
Maternal Alcoholism. www.indiandentalacademy.com
Disorders Caused Due To Unknown Elilogy
Example: Hemi Hyperlepy, Crouzon’s Syndrome, Romberg Syndrome.
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Genetics In Orthodontics: ď Ž
According to the studies and investigations done, it has been suggested that growth of the orofacial structures is not controlled by Genetic factors alone but also by environmental factors.
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The following factors can be attributed as controlling factors in craniofacial growth.
Intrinsic Genetic factors – Genetic factors inherent to the skull tissues
Local epigenetic factors – Genetically determined influences orginationg from adjacent structures. Example: Brain, eyes etc
General epigenetic factors – Genetically determined influences originating from distant structures. Example: Sex hormones etc
Local environmental factors – Local non-genetic influences originating from external environment (local external pressure, muscle forces etc)
General environmental factors – General non-genetic influences originating from the external environment (food, oxygen supple etc) www.indiandentalacademy.com
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The common dental characteristics which can be acquired from the parent to the offspring are:-
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1. Dentition: The formation, eruption, dimensions, form and number of individual teeth have investigated for their genetic composition.
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Formation: From a large number of human fetuses, Kraus (1961) found that the sequence of calcification of deciduous molars is regular and predictable and that each of the four deciduous molars has specific pattern of occlusal calcification at each level of its development. It was postulated that calcification was under genetic control. www.indiandentalacademy.com
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Garn et al (1969) compared both formation among 170 siblings of 62 families by means of serial longitudinal oblique jaw radiographs. similarity
in
the
They
beginning
of
found a greater calcification,
root
formation and apical closures in siblings. Among these, the female pairs exhibited higher sibling correlation in tooth
development,
the
XY
(male)
genotype
introducing a greater degree of heterozygosity than the XX (female) genotype. www.indiandentalacademy.com
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Anomalies of tooth formation have been investigated for their possible hereditary origin. Among the enamel defects hypoplasias and hypocalcification are due to faulty matrix formation and maturation which are probably inherited as a autosomal dominant trait (Witcop 1960). Dentinogenesis imperfecta has been established
as
an
inherited
simple
heterozygous dominant trait. www.indiandentalacademy.com
autosomal
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Eruption: Filipson (1965) studied 45 patients with Turners syndrome and found that they presented a tendency to early eruption of permanent teeth. This confirmed the hypothesis by Garn about genetic control.
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TOOTH DIMENSION ď Ž
The size of the teeth is inherited, but the genetic control is most strongly expressed in certain teeth. Among the anterior teeth the greatest genetic expression is seen in the maxillary lateral incisors, then the mandibular lateral incisors and least in the canine. Romig (1964) found fewer deviations from the normal in the canine and molar than in premolar and incisors of individuals with trisomy 21. www.indiandentalacademy.com
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Number of teeth: Congenitally missing teeth (anodontia and oligodontia) have been to shown to occur in families. Rushton (1953) postulated this as a sex linked recessive trait. However Erwin and Corkern attributed missing third molars and second premolars to a simple autosomal dominant, with variable penetrances. There is a correlation between congenital absence of certain teeth and reduction of size of the remaining ones. Further more it is frequently observed that when there is a congenital absence of teeth, others still unerupted may be absent. www.indiandentalacademy.com
Tooth Form: The anatomic components of teeth have been demonstrated to be under genetic control to a certain extent. Cusps, grooves in number or position and the dental outline at the occlusial and gingival levels. The evidence seems to suggests that each morphologic trait is inherited independently for each morphologic trait is inherited independently for each tooth.
More variable characteristics have been shown to be predominant in certain racial groups. Example: The shovelshaped incisors and short incisors root and enamel pearl bicuspid in mongoloids.
Therefore, the concept that large or small teeth or teeth of peculiar shape or configuration “run in families” www.indiandentalacademy.com
Dental arches: ď Ž
In shape and size, the dental arches present racial variations. Therefore, they may be considered as inherited. Caution should be exercised in this kind of interpretation, since dental arches may be considered to be the product of interaction of the teeth and jaws. It was proved by Stockard (1931) he cross bred different species of dogs and conformed that there is inheritance of dental arch, shape and size. www.indiandentalacademy.com
MALOCCLUSION AND GENETICS
In 1836 Freiderick, G Kussel. After extensive study reported that malocclusion, both skeletal and dental can be transmitted from one generation to the other.
Lundstrom summarizing a number of research investigation of twin studies concluded that about 40% of the dental and facial variations that lead to malocclusion can be attributed to heredity factors.
Between late 1930 and early 1970 Haris JOHNSON WHO CARRIED OUT the Bolton brush growth study from examination of longituidinal cephalometric radiographs and dental casts of sibling, concluded that heritability of craniofacial charactertics were relatively high, but that of dental characteristics were low. www.indiandentalacademy.com
 Chung. et.al conducted his experiments in the Hawaiian population on the effects of out breading on malocclusion. Before the discovery of Hawaii by the Europeans in 18th century. The people had large built broad and well developed jaws and a n usual and distinctive form of mandible known as Rocker Jaw since the gonial angle was smoothly curved. Large scale immigration to the island by the European, Chinese, and Japanese groups resulted in an exceptionally heterogeneous modern population in contrast to the high prevalence of severe mal occlusion that was expected in this population the effect of interacial crossing appeared to be more additive. www.indiandentalacademy.com
Types of Transmission of Malocclusion Repetitive Discontinuous Variable
Ways of production of malocclusion by inherited characteristics Arch length – tooth size discrepancy Disproportion between size and shape of the jaws www.indiandentalacademy.com
Malocclusion of genetic origin - Class II, Division, 1 malocclusion - Harris (1963 & 1975) carried out extensive cephalometric studies to determine the heritability of certain craniofacial parameters in Class II div 1 malocclusion. They showed mandibular retrognathism with mandibular body. - The environment factors influenced were from soft tissue for oral seal during, sleep where the tongue pushed forward proclining the upper anteriors and the lower lip retroclining the lower anteriors. As influencing th sevearity of the overjet. www.indiandentalacademy.com
Class II, Division 2 malocclusion Graber (1972), Hotz (1972), Meskov (1988) and Markovic (1992), stressed the predominant role of genetic factors in etiology of class II div 2 malocclusion. Class III malocclusion A class III malocclusion due to skeletal imbalance between maxilla and mandinble base may result from maxillary deficiency or mandibular excess, or a combination of both. Ellis and Mc Namra (1984), and singh et.al (1997) have found the influence of a distinctive cranial base morphpology with a more acute cranial base angle and shortened posterior cranial base, resulting in more anterior positioning of the glenoid fossa, contributing to mandibular prognathism. www.indiandentalacademy.com
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