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GENETICS

INDIAN DENTAL ACADEMYLeader in continuing Dental Education


INTRODUCTION Genetics ,studies how living organisms inherit

many of the features of their ancestors – for example, children usually look and act like

other people in their family. Genetics tries to identify which features are

inherited, and work out the details of how these features are passed from generation to generation.

It is a rapidly developing science that has reached an advanced level of genetic selection and cloning.


The branch of biology that deals with the facts & laws of heredity & inherited variations.

The science concerned with the structure & function of all genes in different organisms

DEFINITION


William Bateson was a British geneticist. He was the first person to use the term “genetics” to describe the study of heredity and biological inheritance.

HISTORY OF GENETICS


HISTORY OF GENETICS Bateson was the first to suggest the word

"genetics" (from the Greek genno, i.e. to give birth) to describe the study of inheritance and the science of variation .

Bateson first used the term "genetics" publicly at the Third International Conference

on “Plant Hybridization” in London in 1906.


HISTORY OF GENETICS In 1909,Danish botanist Wilhelm Johannsen

proposes the term "gene" (from the Greek word "genos" which means "birth")

1882, German biologist Walter Fleming, by staining cells with dyes, discovers rod- shaped bodies he calls "chromosomes."


Oswald Avery, Colin MacLeod, and Maclyn McCarty report evidence that, at least in bacteria, the molecule that carries genetic information is deoxyribonucleic acid (DNA)


1953,Francis Crick and James Watson determine that the structure of the DNA molecule is a double helix composed of strings of nucleotides and that two parallel strands formed by sugar and phosphate molecules are joined together by the bonding of specific pairs of nitrogenous bases. They share a Nobel Prize for this in 1962.


1955 Joe Hin Tijo

determines that the number of chromosomes in humans is 46.(For 30 years, the number was believed to be 48.)


1961,Sydney Brenner, Francois Jacob, and Matthew Meselson identify the role of Ribonucleic Acid (RNA). They determine that messenger RNA (mRNA) is the molecule that carries the genetic information from DNA in the nucleus out into the cytoplasm and that the cell ultimately uses mRNA to make specific proteins.


Gregor Johann Mendel, an Austrian monk & scientist, publishes his findings on the laws of inheritance based on experiments, begun in 1857, with pea plants


Published in his paper “Experiment on plant hybridization” in 1865 to the Brunn Natural History society.

He laid the foundation for studies of inheritance in the twentieth century and beyond.

“Father of genetics."


Allele: One alternative of a pair or group of genes that could occupy a specific position on a chromosome.

Chromosome: A linear strand of DNA harboring many genes.

DNA: Deoxyribonucleic acid; the molecule in which genetic information is encoded.

Gene: A unit of genetic information that occupies a specific position on a chromosome and comes in multiple versions called alleles.

DEFINITIONS & TERMS


Dominant: An allele producing the same phenotypic effect whether inherited heterozygously or homozygously; an allele that "masks" a recessive allele.

Recessive: An allele producing no phenotypic effect when inherited heterozygously and only affecting the phenotype when inherited homozygously; an allele "masked" by a dominant allele.

DEFINITIONS & TERMS


Genotype: The genetic constitution of an organism.

Phenotype: The physical or observable characteristics of an organism.

Heterozygous: Having a genotype with two different and distinct alleles for the same trait.

Homozygous: Having a genotype with two of the same alleles for a trait.

DEFINITIONS & TERMS


Mendel carried out his experiments, on the common garden pea, Pisum sativum.

His work was not something that was never done, but he was the first to notice that the inheritance units obeyed certain statistical laws.

GREGOR MENDEL


His studies were based on seven traits of peas. The seven traits were qualitative (they could be measured and a value assigned); therefore, specified qualities could be assigned to each plant.

These characteristics were visible and it was through them that he could study the effects of reproduction.


For each of the seven pair of characters, plants with an alternative trait were used as female & other as male.

The plants of unlike characters with which hybridization is first made constitute parent generation ( P1 Generation)


Two contrasting varieties were crossed & the first set of offsprings was known as the first filial or F1 Generation

The progeny of F1 plants obtained due to self-fertilization represents the second filial generation or F2 Generation


Plants obtained from the crossing of two individuals are known as HYBRIDS & the process known as HYBRIDIZATION

In F1 generation, the offspring always resembled only one parent. The character which was manifested was referred to as Dominant & other as Recessive


Based on observations of his experiments on garden pea.

He drew some important conclusions & given three laws:


Mendel’s first experiment with varieties of garden pea that differed only in one visible character : monohybrid experiment

For example, when testing the shape of the seed, crossing one pure-breed round seed with a pure-breed wrinkled seed, all of the offspring were round.

LAW OF DOMINANCE


The one trait - in this case is a wrinkled seed - not expressed in the offspring he called it recessive trait. In each case of this crosses, the round trait was dominant over the wrinkled trait and is said to be the dominant trait. This conclusion is now referred to as Mendel's Law of Dominance


Law of Segregation: when a pair of allelomorphs are brought

together in the hybrid F1, they remain together in the hybrid without blending but separate completely & purely during gamete formation.


Mendel experimented on parents differed in two pairs of characters. Such a cross is known as DIHYBRID CROSS.

Also known as "Inheritance Law", states that the inheritance pattern of one trait will not affect the inheritance pattern of another.

LAW OF INDEPENDENT ASSORTMENT


While Mendel's experiments with mixing one trait always resulted in a 3:1 ratio between dominant and recessive phenotypes, his experiments with mixing two traits (dihybrid cross) showed 9:3:3:1 ratios But the 9:3:3:1 shows that each of the two genes are independently inherited with a 3:1 ratio.

LAW OF INDEPENDENT ASSORTMENT



CONCLUSION: That different traits are inherited

independently of each other, so that there is no relation.


Dominance is absent i.e. the f1 exhibit neither of two phenotypes presented in parents. The hybrid individual resemble neither parent & are intermediate between those of two parents

Thus both alleles have almost equal effect on the phenotype, resulting in intermediate character of hybrid

INCOMPLETE DOMINANCE


Both allelic genes of a genetic genes of a genetic triad, one equally expressive i.e. the dominant character is not able to suppress the recessive character & thus both the characters appears side by side F1 hybrids

CODOMINANCE


Human chromosome preparations first made by FLEMMING (1882)

In 1903, Sutton and Boveri , independently, proposed that it was the interaction between these chromosomes that lead to the phenomenon of inheritance.

First determination of chromosome no.: WINIWARTER (1912), reported 2n=48.

Human Y chromosome: PAINTER (1923)

CHROMOSOME


Correct human chromosome 2n=46: TIJO & LEVAN (1956)

Autosome term: MONTGOMERY (1904) Sex chromosome / heterosomes: WILSON

(1906) Chromosomes are organized structures of

DNA and proteins that are found in cells Cells contained a nucleus and the nucleus

had threadlike substances called chromosomes


The word chromosome comes from (chroma, color) and (soma, body) due to their property of being stained very strongly by some dyes.

The total complement of genes in an organism or cell is known as its genome, which may be stored on one or more chromosomes; the region of the chromosome at which a particular gene is located is called its locus.


A chromosome is formed from a single DNA molecule that contains many genes. A chromosomal DNA molecule contains three specific nucleotide sequences which are required for replication: a DNA replication origin; a centromere to attach the DNA to the mitotic spindle.; a telomere located at each end of the linear chromosome.


There are 46 chromosomes in the normal human – 23 pairs.

The members of each pair match with respect to the genetic information they carry.

One chromosome of the pair is inherited from the father, and one from the mother, and further, one is transmitted to the child.

22 pairs are alike in males and females – known as autosomes

1 pair differs – the sex chromosomes.

HUMAN CHROMOSOME


the female sex chromosomes – there are two X chromosome.

In the male, there is one X chromosome and one Y chromosome which is smaller than the X chromosome.

There are 2 types of cell division – Mitosis – normal cell division, by virtue of

which the body grows – it results in 2 daughter cells, identical to the parent cell in genetic makeup, and number of chromosomes.


Meiosis – This results in the production of reproductive cells (gametes). Each of which have only 23 chromosomes.


MEIOSIS


MITOSIS


Chromosomal abnormalities can be of the following types:-

Abnormality in – Autosomes - Sex chromosomes Abnormality in – Number - Structure

CHROMOSOMAL ABNORMALITIES


Loss or gain of a single chromosome is known as aneuploidy

Polyploidy – is a gain of the whole chromosome set – ie – 3N or 4N number of chromosomes.

Monosomy – is the loss of a single chromosome.


Trisomy – This is the gain of a single chromosome.

Lejeune (1959) was the first to show that patients with Down’s syndrome had an extra Chromosome 21.

The main cause of trisomy is the failure of homologous chromosomes to separate during meiosis. This is known as non-disjunction.


Deletions: A portion of the chromosome is missing or deleted. Known disorders include Wolf-Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4.

STRUCTURAL ABNORMALITIES


Duplications: A portion of the chromosome is duplicated, resulting in extra genetic material. Known disorders include Charcot-Marie-Tooth disease type 1A which may be caused by duplication of the gene encoding peripheral myelin protein 22 (PMP22) on chromosome 17.



Inversions: A portion of the chromosome has broken off, turned upside down and reattached, therefore the genetic material is inverted.



Translocations: When a portion of one chromosome is transferred to another chromosome. There are two main types of translocations.



In a reciprocal translocation, segments from two different chromosomes have been exchanged.


Robertsonian translocation, an entire chromosome has attached to another at the centromere; these only occur with chromosomes 13, 14, 15, 21 and 22.


If a deletion occurs at 2 ends of a chromosome, such that the resultant ends have complementary base pairs, they tend to join, and form a ring chromosome.


Abnormality of number

Seen in many syndromes – Klinefelter’s syndrome – XXY Turner’s syndrome – females with only 1 X

chromosome Multiple X – females with 3 or 4 X

chromosomes XYY males

SEX CHROMOSOME ABNORMALITIES


Abnormalites of Structure

Isochromosome X – a long X chromosome – which results from deletion of the short arms of the X chromosome and duplication of the long arm.


A gene can be defined as a region of DNA that controls a hereditary characteristic. It usually corresponds to a sequence used in the production of a specific protein or RNA.

OR Genes are instruction manuals for our

bodies. They are the direction for building all proteins that make our bodies function.

GENES


A gene carries biological information in a form that must be copied and transmitted from each cell to all its progeny. This includes the entire functional unit: coding DNA sequences, non-coding regulatory DNA sequences, and introns.

1910,Thomas Hunt Morgan argued that genes are on chromosomes.


genes are specific segments of DNA located along chromosomes. Because different genes are made up of different sequences of bases, different genes contain different information about the body’s traits and functions.

STRUCTURE OF GENES


Genes have both coding and non-coding sequences. Coding sequences are those sequences that are used as a template for protein synthesis during the process of translation. The coding sequences of a gene are called exons.


Non-coding sequences do not provide information about the protein for which the gene codes, but these sequences often play important roles in regulating gene expression and protein synthesis. There are different types of non-coding sequences within each gene, including introns, promoters


the coding sequences, called exons, are separated by intervening, non-coding sequences called introns.

Whereas exons contain genetic information that will be used to make the protein, introns do not.

Both exonic and intronic sequences are transcribed into an RNA molecule, but only exons contribute to the protein.



Before being translated into a protein, the RNA undergoes splicing, a process whereby the intronic RNA sequences are removed and discarded and the exonic RNA sequences are joined together to give a shorter, “mature” messenger RNA (mRNA) molecule.

Splicing occurs specifically at the exon/intron boundaries; these boundaries are called the splice junctions, and they are characterized by particular sequences.


Like introns, the promoter of a gene also does not code for protein. However, the promoter is very important for regulating whether a gene is expressed or not expressed. When a gene is expressed (turned “on”), the gene is transcribed into an mRNA molecule.

When a gene is not expressed (turned “off”), the gene is not transcribed; an mRNA molecule is not made.


The process of producing a biologically functional molecule of either RNA or protein is called gene expression, and the resulting molecule itself is called a gene product.


Defined as a sudden inheritable genetic change, altering the genetic message of a cell.

Heritable change in the structure of a gene/ chromosome/ change in chromosome no.

Mainly responsible for variations in organisms

First seen in 18th century : SETH H WRIGHT (new England farmer) in a male ANCON SHEEP

Term first used: Dutch Botanist HUGO DE VRIES (1901)

MUTATIONS


Depending on kind of cell in which mutation occurs

Somatic: malignant or cancerous growth is a kind of mutation which is localized & not transmitted to offsprings

Germinal: occurs in germ cells during gametogenesis

TYPES


AMATTO (1950)

Gene mutation Chromosomal mutation Genomatic mutation (change in no.)

CLASSIFICATION


Change in gene duplication: gene mutation Mutant & original gene located at same

fixed point on a particular chromosome & since gene is situated at a fixed point; POINT MUTATION

Mostly include alteration in the sequences of nucleotides in the nucleic acid which form the genetic material

GENE MUTATION


Change in chromosome structure/ morphology: chromosomal mutation

Do not involve changes in the no. of chromosomes but result from changes in the no. or sequence of genes on chromosomes

CHROMOSOMAL MUTATIONS


Changes in chromosome no.: genomatic mutation(heteroploidy)

2 types Aneuploidy euploidy

GENOMATIC MUTATION


It is the presence of a chromosome no. which is different then the multiple of basic chromosome no.

Either loss (hypoploidy) or addition (hyperploidy) of one or more chromosome occurs.

ANEUPLOIDY


Mutations which involve addition of complete set of chromosome.

EUPLOIDY


Deoxyribonucleic acid (DNA) is the macromolecule that stores the information necessary to build structural and functional cellular components.

DNA normally exists as a double-stranded molecule, coiled into the shape of a double-helix.

DNA


Double helix model has two strands of DNA with nucleotides pointing inwards, each matching a complementary nucleotide on other strand .


This shows that genetic information exists in the sequence of nucleotides on each strand of DNA.

Information is held in the sequence of repeating units along the DNA chain.


These units are four types of nucleotides

A,G,T,C They pair up to hold

the two strands together

An A nucleotide goes opposite to T & G opposite to C.

This exact pairing: Base pairing


The 2 chains are held together by hydrogen bonds between the nitrogenous bases which point in towards the centre of the helix.

Two chains have opposite orientation, and are said to be in an anti – parallel orientation


When a gene is read by a cell the DNA sequence is copied into a very similar molecule called RNA: transcription

This messenger RNA molecule is then used to produce a corresponding amino acid sequence through a process called translation


When genes are passed from a parents to a child they are copied. Parents keep the same no. of genes as they had before & just passes on the new copies to their offsprings.

Genes are always copied each time a cell divides into two new cells.

Process which copies DNA: replication

REPLICATION


Inheritance is the process by which characteristics of parents are transferred to offspring.

Children inherit traits, disorders, and characteristics from their parents. Children tend to resemble their parents especially in physical appearance. However they may also have the same mannerisms, personality, and a lot of the time the same mental abilities or disabilities.

GENETIC INHERITANCE


Genetic disorders can be of 3 main types :- Single gene disorders – these occur due to

mutations of single genes. They show typical pedigree patterns and are rare - 1 in 2000 or less.

Chromosome disorders – the disorder occurs due to an excess or deficiency of whole chromosomes or chromosome segments. They show characteristic features, and are relatively more common than single gene disorders - 7 in 1000 births.


Multifactorial disorder – These are caused due to a combination of genetic and environmental factors. They are the most common of the genetic disorders and do no show the typical pedigree patterns on single gene disorders.


Single Gene disorders.

These can be – Autosomal dominant Autosomal recessive Sex linked dominant Sex linked recessive


Two copies of the gene must be mutated for a person to be affected by an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Two unaffected people who each carry one copy of the mutated gene have a 25% chance with each pregnancy of having a child affected by the disorder.

Eg. Sickel cell anaemia, Muscular dystrophy

AUTOSOMAL RECESSIVE


Only one mutated copy of the gene is needed for a person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. There is a 50% chance that a child will inherit the mutated gene.

Eg. Achondroplasia Osteogenesis imperfecta

some forms of Amelogenesis imperfecta

AUTOSOMAL DOMINANT


X-linked dominant disorders are caused by mutations in genes on the X chromosome.

Females are more frequently affected than males, and the chance of passing on an X-linked dominant disorder differs between men and women.

The sons of a man with an X-linked dominant disorder will not be affected, and his daughters will all inherit the condition.

X-LINKED DOMINANT


A woman with an X-linked dominant disorder has a 50% chance of having an affected daughter or son with each pregnancy


X-linked recessive disorders are also caused by mutations in genes on the X chromosome. Males are more frequently affected than females, and the chance of passing on the disorder differs between men and women.

The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the mutated gene

X-LINKED RECESSIVE


With each pregnancy, a woman who carries an X-linked recessive disorder has a 50% chance of having sons who are affected and a 50% chance of having daughters who carry one copy of the mutated gene.


Y-linked disorders are caused by mutations on the Y chromosome.

Only males can get them, and all of the sons of an affected father are affected.

Females are not affected as they do not have a Y chromosome.

Y-LINKED


This type of inheritance, also known as maternal inheritance, applies to genes in mitochondrial DNA.

MITOCHONDRIAL INHERITANCE


Intermediate inheritance. Some mutant genes are only partially

expressed in the heterozygote. This is known as incomplete dominance, or intermediate inheritance.

An example is sickle cell anaemia. A person homozygous for the mutant gene, shows typical sickling of the RBCs. The heterozygote on the other hand shown normal RBCs in normal condition.


But if the heterozygote is exposed to low oxygen tension, as in high altitude travel etc, the RBCs change from the normal shape to sickle shape. These people are said to have the sickle cell trait.


Codominance. In some cases, the alleles for a particular

characteristic may be different, but both may be expressed. This is known as co-dominance. E.g. – both the antigens A and B are present in blood group AB.


A person's cells hold the exact genes that originated from the sperm and egg of his parents at the time of conception. The genes of a cell are formed into long strands of DNA. Most of the genes that control characteristic are in pairs, one gene from mom and one gene from dad

MECHANISM OF INHERITANCE


Everybody has 22 pairs of chromosomes (autosomes) and two more genes called sex-linked chromosomes. Females have two X (XX) chromosomes and males have an X and a Y (XY) chromosome.


However, the modern science of genetics, which seeks to understand the process of inheritance, only began with the work of Gregor Mendel in the mid-nineteenth century.

Although he did not know the physical basis for heredity, Mendel observed that organisms inherit traits in a discrete manner—these basic units of inheritance are now called GENES


Discovered in 1983,by WALTER JACOB GEHRING homeobox genes, and the proteins they encode, the homeodomain proteins, have turned out to play important roles in the developmental processes of many multicellular organisms.

A homeobox is a DNA sequence found within genes that are involved in the regulation of development (morphogene) of animals,

fungi and plants. Genes that have a homeobox are called homeobox genes and form the homeobox gene family.

HOMEOBOX GENES


A homeobox is a DNA sequence found within genes that are involved in the regulation of development (morphogenesis) of animals, fungi and plants. Genes that have a homeobox are called homeobox genes and form the homeobox gene family.

Homeobox genes encode transcription factors which typically switch on cascades

of other genes. The homeodomain binds DNA in a specific manner


Hox genes: Hox genes are a subgroup of homeobox genes. In vertebrates these genes are found in gene clusters on the chromosomes. In mammals four such clusters exist, called Hox clusters. The gene name "Hox" has been restricted to name Hox cluster genes in vertebrates. Only genes in the HOX cluster should be named Hox genes. So note: homeobox genes are NOT Hox genes, Hox genes are a subset of homeobox genes.


homeodomain: a DNA-binding domain, usually about 60 amino acids in length, encoded by the homeobox.

homeobox: a fragment of DNA of about 180 basepairs (not counting introns), found in homeobox genes.


These genes, also known as HOX genes, form hox codes, which specify the position a cell should occupy, and the structure that cell should develop into. Interestingly, they have an anterior-posterior arrangement. The anterior genes coding for anterior structures, and posterior genes coding for posterior structures.


Humans generally contain homeobox genes in four clusters:

HOXA (or sometimes HOX1) - chromosome 7 HOXA1, HOXA2, HOXA3, HOXA4

HOXB - chromosome 17 HOXB1, HOXB2, HOXB3, HOXB4

HOXC - chromosome 12 HOXC4, HOXC5, HOXC6

HOXD - chromosome 2 HOXD1, HOXD3, HOXD4, HOXD8

HUMAN GENES


Mutation Mutations to homeobox genes can produce

easily visible phenotypic changes. Duplication of homeobox genes can produce

new body segments



Amelin & enamelin: enamel protein BMP 2&4: tooth formation DSPP: defective mineralization of teeth BSP: mineralization of bone & cementum MSX 1&2: incisors BARX & DLX-2: molars

GENES RESPONSIBLE:


Dr. V.Singh, Dr. D.K.Jain, Book Of Biology, 3rd edi., 2001, Pgs. 781, 782,819-825

Richard Tencate, Oral Histology- Development, Structure & Function,5th edi., Mosby

Inderbir Singh, Human Embryology,7th edit., MacMillan

http://faculty.uca.edu.com www. Wikipedia.co

BIBLIOGRAPHY

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