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Genetic and its role in oral disease Dr. Reem Adeeb Luc-3- 2022/12/14 Introduction Genetics; is the study of genes, genetic variations, and hereditary of living organisms. It is the field of biology intersecting with various life sciences and strongly a...

Genetic and its role in oral disease Dr. Reem Adeeb Luc-3- 2022/12/14 Introduction Genetics; is the study of genes, genetic variations, and hereditary of living organisms. It is the field of biology intersecting with various life sciences and strongly associated with the study of information system The study is done at all levels from molecules to population. The basic study of genetics includes: Study of the gene, DNA, and chromosomes. Inheritance and its various patterns. Genetic mutation. Genetic variation. Genes and environmental interplay. Family medical history and genes Gene is the basic unit of hereditary; it is the segment of DNA that is passed down from parents to offspring. It is responsible For protein formation, cell structure, and function. DNA is a double-stranded structure that contains complementary genetic Informa on. During the replication of DNA (s phase) if there is a matching error in the complementary structure, a protein repairs it and keeps the genome intact but with faulty repair, protein errors accumulate leading to genetic mutation: a permanent alteration. Genetic mutation is of two ty Hereditary: Inherited from a parent and present throughout a person’s life and present in every cell of the body. Acquired: Occur at some point during a person’s life due to environmental factors and is present in certain cells. During the mutation of DNA, in DNA codon frameshift mutation occurs due to substitution, insertion, or deletion resulting in defective protein which is either inactive or disease-causing Tooth is a specialized unit of the maxillofacial skeleton formed by a series of complex steps. Tooth development is under genetic control and is regulated by inductive interactions between epithelial and mesenchymal cells. The contribution of hereditary factors in the pathogenesis of dental caries, periodontal problems, dental Anomalies and other oral and maxillofacial disorders are becoming increasingly evident in dentistry. Identification of the underlying cause of a condition starts with the localization of its defective gene in The human genome. Progression made by human genome projects over the years has greatly increased the feasibility of mapping inherited conditions. The role of genetics has been increasingly recognized in the understanding of various dental diseases and anomalies tooth What is DNA? DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA). The information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases, and more than 99 percent of those bases are the same in all people. The order, or sequence, of these bases, determines the information available for building and maintaining an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences. DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The structure of the double helix is somewhat like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder. An important property of DNA is that it can replicate, or make copies of itself. Each strand of DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell. What is a gene? A gene is the basic physical and functional unit of heredity. Genes, which are made up of DNA, act as instructions to make molecules called proteins. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. The Human Genome Project has estimated that humans have between 20,000 and 25,000 genes. Every person has two copies of each gene, one inherited from each parent. Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different between people. Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features What is a chromosome? In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called chromosomes. Each chromosome is made up of DNA tightly coiled many times around proteins called histones that support its structure. Chromosomes are not visible in the cell’s nucleus—not even under a microscope—when the cell is not dividing. However, the DNA that makes up chromosomes becomes more tightly packed during cell division and is then visible under a microscope. Most of what researchers know about chromosomes was learned by observing chromosomes during cell division. Each chromosome has a constriction point called the centromere, which divides the chromosome into two sections, or “arms.” The short arm of the chromosome is labeled the “p arm.” The long arm of the chromosome is labeled the “q arm.” The location of the centromere on each chromosome gives the chromosome its characteristic shape and can be used to help describe the location of specific genes. What are proteins and what do they do? Proteins are large, complex molecules that play many critical roles in the body. They do most of the work in cells and are required for the structure, function, and regulation of the body’s tissues and organs. Proteins are made up of hundreds or thousands of smaller units called amino acids, which are attached to one another in long chains. There are 20 different types of amino acids that can be combined to make a protein. The sequence of amino acids determines each protein’s unique 3-dimensional structure and its specific function. Proteins can be described according to their large range of functions in the body, listed in alphabetical order How do genes direct the production of proteins? Most genes contain the information needed to make functional molecules called proteins. (A few genes produce other molecules that help the cell assemble proteins.) The journey from gene to protein is complex and tightly controlled within each cell. It consists of two major steps: transcription and translation. Together, transcription and translation are known as gene expression. During the process of transcription, the information stored in a gene’s DNA is transferred to a similar molecule called RNA (ribonucleic acid) in the cell nucleus. Both RNA and DNA are made up of a chain of nucleotide bases, but they have slightly different chemical properties. The type of RNA that contains the information for making a protein is called messenger RNA (mRNA) because it carries the information, or message, from the DNA out of the nucleus into the cytoplasm. Translation, the second step in getting from a gene to a protein, takes place in the cytoplasm. The mRNA interacts with a specialized complex called a ribosome, which “reads” the sequence of mRNA bases. Each sequence of three bases, called a codon, usual codes for one particular amino acid. (Amino acids are the building blocks of proteins.) A type of RNA called transfer RNA (tRNA) assembles the protein, one amino acid at a time. Protein assembly continues until the ribosome encounters a “stop” codon (a sequence of three bases that does not code for an amino acid). The flow of information from DNA to RNA to proteins is one of the fundamental principles of molecular biology. It is so important that it is sometimes called the “central dogma.” What is a gene mutation and how do mutations occur? A gene mutation is a permanent change in the DNA sequence that makes up a gene. Mutations range in size from a single DNA building block (DNA base) to a large segment of a chromosome. Gene mutations occur in two ways: they can be inherited from a parent or acquired during a person’s lifetime. Mutations that are passed from parent to child are called hereditary mutations or germline mutations (because they are present in the egg and sperm cells, which are also called germ cells). This type of mutation is present throughout a person’s life in virtually every cell in the body. Mutations that occur only in an egg or sperm cell, or those that occur just after fertilization, are called new (de novo) mutations. De novo mutations may explain genetic disorders in which an affected child has a mutation in every cell, but has no family history of the disorder. Acquired (or somatic) mutations occur in the DNA of individual cells at some time during a person’s life. These changes can be caused by environmental factors such as ultraviolet radiation from the sun, or can occur if a mistake is made as DNA copies itself during cell division. Acquired mutations in somatic cells (cells other than sperm and egg cells) cannot be passed on to the next generation. Mutations may also occur in a single cell within an early embryo. As all the cells divide during growth and development, the individual will have some cells with the mutation and some cells without the genetic change. This situation is called mosaicism. Some genetic changes are very rare; others are common in the population. Genetic changes that occur in more than 1 percent of the population are called polymorphisms. They are common enough to be considered a normal variation in the DNA. Polymorphisms are responsible for many of the normal differences between people such as eye color, hair color, and blood type. Although many polymorphisms have no negative effects on a person’s health, some of these variations may influence the risk of developing certain disorders. Do all gene mutations affect health and development? No; only a small percentage of mutations cause genetic disorders— most have no impact on health or development. For example, some mutations alter a gene’s DNA base sequence but do not change the function of the protein made by the gene. Often, gene mutations that could cause a genetic disorder are repaired by certain enzymes before the gene is expressed (makes a protein). Each cell has a number of pathways through which enzymes recognize and repair mistakes in DNA. Because DNA can be damaged or mutated in many ways, DNA repair is an important process by which the body protects itself from disease. A very small percentage of all mutations actually have a positive effect. These mutations lead to new versions of proteins that help an organism and its future generations better adapt to changes in their environment. For example, a beneficial mutation could result in a protein that protects the organism from a new strain of bacteria. Mutations Mutation – sudden genetic change (change in base pair sequence of DNA) Can be : Harmful mutations – organism less able to survive: genetic disorders, cancer, death Beneficial mutations – allows organism to better survive: provides genetic variation Neutral mutations – neither harmful nor helpful to organism Mutations can occur in 2 ways: chromosomal mutation or gene/point mutation Chromosomal mutation: less common than a gene mutation more drastic – affects entire chromosome, so affects many genes rather than just one caused by failure of the homologous chromosomes to separate normally during meiosis chromosome pairs no longer look the same – too few or too many genes, different shape  Examples: Down’s syndrome – (Trisomy 21) 47 chromosomes, extra chromosome at pair #21 Turner’s syndrome – only 45 chromosomes, missing a sex chromosome (X) Girls affected – short, slow growth, heart problems Gene or Point Mutation most common and least drastic only one gene is altered  Examples: Recessive gene mutations: Sickle cell anemia – red blood cells are sickle shaped instead of round and cannot carry enough oxygen to the body tissues – heterozygous condition protects people from malaria