Introduction

THE GENE
The term gene was coined by Wilhelm Johansen in 1909 to describe a heritable factor responsible for the transmission and expression of a given biological character, but without reference to any particular theory of heritance. Therefore, in its original context, the gene had no specific material basis and could be treated purely in abstract terms, as it is in the study of transmission genetics.

A gene is a unit of heredity in a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living things depend on genes, as they specify all proteins and functional RNA chains. Genes hold the information to build and maintain an organism's cells and pass genetic traits to offspring, although some organelles (e.g. mitochondria) are self-replicating and are not coded for by the organism's DNA. All organisms have many genes corresponding to various different biological traits, some of which are immediately visible, such as eye color or number of limbs, and some of which are not, such as blood type or increased risk for specific diseases, or the thousands of basic biochemical processes that comprise life.

Genetics

GENETICS

Genetics is the study of genes, and tries to explain what they are and how they work. Genes are how living organisms inherit features from their ancestors; for example, children usually look like their parents because they have inherited their parents' genes. Genetics tries to identify which features are inherited, and explain how these features are passed from generation to generation.

In genetics, a feature of a living thing is called a "trait". Some traits are part of an organism's physical appearance; such as a person's eye-color, height or weight. Other sorts of traits are not easily seen and include blood types or resistance to diseases. The way our genes and environment interact to produce a trait can be complicated. For example, the chances of somebody dying of cancer or heart disease seems to depend on both their genes and their lifestyle. Some traits are inherited through our genes, so tall and thin people tend to have tall and thin children; such traits which result due to inheritance alone are called genotypes. Other traits come from interactions between our genes and the environment, so a child might inherit the tendency to be tall, but if they are poorly nourished, they will still be short; such traits which are manifested due to the combined action of inherited genes and environmental circumstances are called as phenotypes.

Genes are made from a long molecule called DNA, which is copied and inherited across generations. DNA is made of simple units that line up in a particular order within this large molecule. The order of these units carries genetic information, similar to how the order of letters on a page carries information. The language used by DNA is called the genetic code, which lets organisms read the information in the genes. This information is the instructions for constructing and operating a living organism. The information within a particular gene is not always exactly the same between one organism and another, so different copies of a gene do not always give exactly the same instructions. Each unique form of a single gene is called an allele. As an example, one allele for the gene for hair color could instruct the body to produce a lot of pigment, producing black hair, while a different allele of the same gene might give garbled instructions that fail to produce any pigment, giving white hair. Mutations are random changes in genes, and can create new alleles. Mutations can also produce new traits, such as when mutations to an allele for black hair produce a new allele for white hair. This appearance of new traits is important in evolution.

DNA repair and maintenance

DNA repair

DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1 million individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages.

The DNA repair ability of a cell is vital to the integrity of its genome and thus to its normal functioning and that of the organism. Many genes that were initially shown to influence life span have turned out to be involved in DNA damage repair and protection.Failure to correct molecular lesions in cells that form gametes can introduce mutations into the genomes of the offspring and thus influence the rate of evolution.

Multiple chromosomes due to DNA damage

DNA damage
DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 1,000 to 1,000,000 molecular lesions per cell per day.While this constitutes only 0.000165% of the human genome's approximately 6 billion bases (3 billion base pairs), unrepaired lesions in critical genes (such as tumor suppressor genes) can impede a cell's ability to carry out its function and appreciably increase the likelihood of tumor formation. The vast majority of DNA damage affects the primary structure of the double helix; that is, the bases themselves are chemically modified. These modifications can in turn disrupt the molecules' regular helical structure by introducing non-native chemical bonds or bulky adducts that do not fit in the standard double helix. Unlike proteins and RNA, DNA usually lacks tertiary structure and therefore damage or disturbance does not occur at that level. DNA is, however, supercoiled and wound around "packaging" proteins called histones (in eukaryotes), and both superstructures are vulnerable to the effects of DNA damage.

Repair mechanisms:

DNA repair mechanisms are essential for survival and integrity, and in animals the repair of DNA is particularly important because mutations which affect cell growth cause cancer. A number of human diseases resulting from the loss of DNA repair function or of a cellular response to DNA damage are listed:

 1. Direct reversal repair :

Single-strand and Double-
strand DNA damage

There are three classes of lesion subject to direct reversal repair:

         1. Direct repair of nicks:

         2. Certain UV photoproducts can be repaired by photoreactivation:

         3. Direct repair of alkylated bases:

2. Excision repair:

      Base excision repair

      Nucleotide excision repair

3. Mismatch repair

4. Recombination repair

Genetics Engineering

Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest. The introduction of new DNA does not require the use of classical genetic methods, however traditional breeding methods are typically used for the propagation of recombinant organisms.

Elements of Genetic Engineering

An organism that is generated through the introduction of recombinant DNA is considered to be a genetically modified organism. The first organisms genetically engineered were bacteria in 1973 and then mice in 1974. Insulin-producing bacteria were commercialized in 1982 and genetically modified food has been sold since 1994. The most common form of genetic engineering involves the insertion of new genetic material at an unspecified location in the host genome. This is accomplished by isolating and copying the genetic material of interest using molecular cloning methods to generate a DNA sequence containing the required genetic elements for expression, and then inserting this construct into the host organism. Other forms of genetic engineering include gene targeting and knocking out specific genes via engineered nucleases such as zinc finger nucleases or engineered homing endonucleases.


Genetic engineering techniques have been applied in numerous fields including research, biotechnology, and medicine. Medicines such as insulin and human growth hormone are now produced in bacteria, experimental mice such as the oncomouse and the knockout mouse are being used for research purposes and insect resistant and/or herbicide tolerant crops have been commercialized. Genetically engineered plants and animals capable of producing biotechnology drugs more cheaply than current methods (called pharming) are also being developed and in 2009 the FDA approved the sale of the pharmaceutical protein antithrombin produced in the milk of genetically engineered goats.

History of Genetics

The history of genetics started with the work of the Augustinian friar Gregor Johann Mendel. His work on pea plants, published in 1866, described what came to be known as Mendelian Inheritance. In the centuries before—and for several decades after—Mendel's work, a wide variety of theories of heredity proliferated.

1900 marked the "rediscovery of Mendel" by Hugo de Vries, Carl Correns and Erich von Tschermak, and by 1915 the basic principles of Mendelian genetics had been applied to a wide variety of organisms—most notably the fruit fly Drosophila melanogaster. Led by Thomas Hunt Morgan and his fellow "drosophilists", geneticists developed the Mendelian, which was widely accepted by 1925. Alongside experimental work, mathematicians developed the statistical framework of population genetics, bring genetical explanations into the study of evolution.

With the basic patterns of genetic inheritance established, many biologists turned to investigations of the physical nature of the gene. In the 1940s and early 1950s, experiments pointed to DNA as the portion of chromosomes (and perhaps other nucleoproteins) that held genes. A focus on new model organisms such as viruses and bacteria, along with the discovery of the double helical structure of DNA in 1953, marked the transition to the era of molecular genetics.

Nucleotide

Ribose structure

Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides play central roles in metabolism, in which capacity they serve as sources of chemical energy (adenosine triphosphate and guanosine triphosphate), participate in cellular signaling (cyclic guanosine monophosphate and cyclic adenosine monophosphate), and are incorporated into important cofactors of enzymatic reactions (coenzyme A, flavin adenine dinucleotide, flavin mononucleotide, and nicotinamide adenine dinucleotide phosphate).

A nucleotide is composed of a nucleobase (nitrogenous base), a five-carbon sugar (either ribose or 2'-deoxyribose), and one to three phosphate groups. Together, the nucleobase and sugar comprise a nucleotide. The phosphate groups form bonds with either the 2, 3, or 5-carbon of the sugar, with the 5-carbon site most common. Cyclic nucleotides form when the phosphate group is bound to two of the sugar's hydroxyl groups. Ribonucleotides are nucleotides where the sugar is ribose, and deoxyribonucleotides contain the sugar deoxyribose. Nucleotides can contain either a purine or a pyrimidine base.
 

Nucleic acids are polymeric macromolecules made from nucleotide monomers. In DNA, the purine bases are adenine and guanine, while the pyrimidines are thymine and cytosine. RNA uses uracil in place of thymine. Adenine always pairs with thymine by 2 hydrogen bonds, while guanine pairs with cytosine through 3 hydrogen bonds, each due to their unique structures.

Mutation

In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic chemicals, as well as errors that occur during meiosis or DNA replication.They can also be induced by the organism itself, by cellular processes such as hypermutation.

Mutation can result in several different types of change in sequences;(DNA) these can either have no effect, alter the product of a gene, or prevent the gene from functioning properly or completely. Studies in the fly Drosophila melanogaster suggest that if a mutation changes a protein produced by a gene, this will probably be harmful, with about 70 percent of these mutations having damaging effects, and the remainder being either neutral or weakly beneficial.Due to the damaging effects that mutations can have on genes, organisms have mechanisms such as DNA repair to remove mutations. Viruses that use RNA as their genetic material have rapid mutation rates, which can be an advantage since these viruses will evolve constantly and rapidly, and thus evade the defensive responses of e.g. the human immune system.

Heridity

Heredity is the passing of traits to offspring (from its parent or ancestors). This is the process by which an offspring cell or organism acquires or becomes predisposed to the characteristics of its parent cell or organism. Through heredity, variations exhibited by individuals can accumulate and cause some species to evolve. The study of heredity in biology is called genetics, which includes the field of epigenetics.

Types of Heridity

  

An allele is said to be dominant if it is always expressed in the appearance of an organism (phenotype). For example, in peas the allele for green pods, G, is dominant to that for yellow pods, g. Since the allele for green pods is dominant, pea plants with the pair of alleles GG (homozygote) or Gg (heterozygote) will have green pods. The allele for yellow pods is recessive. The effects of this allele are only seen when it is present in both chromosomes, gg (homozygote).

The description of a mode of biological inheritance consists of three main categories:

1. Number of involved loci

• Monogenetic (also called "simple") – one locus
• Oligogenetic – few loci
• Polygenetic – many loci

2. Involved chromosomes

• Autosomal – loci are not situated on a sex chromosome
• Gonosomal – loci are situated on a sex chromosome
  • X-chromosomal – loci are situated on the X-chromosome (the more common case)
  • Y-chromosomal – loci are situated on the Y-chromosome
• Mitochondrial – loci are situated on the mitochondrial DNA

3. Correlation genotype–phenotype

• Dominant
• Intermediate (also called "codominant")
• Recessive

These three categories are part of every exact description of a mode of inheritance in the above order. Additionally, more specifications may be added as follows:

4. Coincidental and environmental interactions

• Penetrance
  • Complete
  • Incomplete (percentual number)
• Expressivity
  • Invariable
  • Variable
• Heritability (in polygenetic and sometimes also in oligogenetic modes of inheritance)
• Maternal or paternal imprinting phenomena (also see epigenetics)

5. Sex-linked interactions

• Sex-linked inheritance (gonosomal loci)
• Sex-limited phenotype expression (e.g., cryptorchism)
• Inheritance through the maternal line (in case of mitochondrial DNA loci)
• Inheritance through the paternal line (in case of Y-chromosomal loci)

6. Locus–locus interactions

• Epistasis with other loci (e.g., overdominance)
• Gene coupling with other loci (also see crossing over)
• Homozygotous lethal factors
• Semi-lethal factors

 

DNA and RNA

DNA (Deoxyribonucleic acid)

Structure of  DNA

DNA is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms (with the exception of RNA viruses). The main role of DNA molecules is the long-term storage of information. DNA is often compared to a set of blueprints, like a recipe or a code, since it contains the instructions needed to construct other components of cells, such as proteins and RNA molecules. The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information. Along with RNA and proteins, DNA is one of the three major macromolecules that are essential for all known forms of life.

DNA consists of two long polymers of simple units called nucleotides, with backbones made of sugars and phosphate groups joined by ester bonds. These two strands run in opposite directions to each other and are therefore anti-parallel. Attached to each sugar is one of four types of molecules called nucleobases (informally, bases). It is the sequence of these four nucleo bases along the backbone that encodes information. This information is read using the genetic code, which specifies the sequence of the amino acids within proteins. The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription.

In living organisms DNA does not usually exist as a single molecule, but instead as a pair of molecules that are held tightly together.These two long strands entwine like vines, in the shape of a double helix. The nucleotide repeats contain both the segment of the backbone of the molecule, which holds the chain together, and a nucleobase, which interacts with the other DNA strand in the helix. A nucleobase linked to a sugar is called a nucleoside and a base linked to a sugar and one or more phosphate groups is called a nucleotide. Polymers comprising multiple linked nucleotides (as in DNA) is called a polynucleotide. 

RNA (Ribonucleic acid)

Structure of RNA

RNA is one of the three major macromolecules (along with DNA and proteins) that are essential for all known forms of life.

Like DNA, RNA is made up of a long chain of components called nucleotides. Each nucleotide consists of a nucleobase (sometimes called a nitrogenous base), a ribose sugar, and a phosphate group. The sequence of nucleotides allows RNA to encode genetic information. All cellular organisms use messenger RNA (mRNA) to carry the genetic information that directs the synthesis of proteins. In addition, some viruses use RNA instead of DNA as their genetic material; perhaps a reflection of the suggested key role of RNA in the evolutionary history of life on Earth. The chemical structure of RNA is very similar to that of DNA, with two differences: (a) RNA contains the sugar ribose, while DNA contains the slightly different sugar deoxyribose (a type of ribose that lacks one oxygen atom), and (b) RNA has the nucleobase uracil while DNA contains thymine. Uracil and thymine have similar base-pairing properties.

Unlike DNA, most RNA molecules are single-stranded. Single-stranded RNA molecules adopt very complex three-dimensional structures, since they are not restricted to the repetitive double-helical form of double-stranded DNA. RNA is made within living cells by RNA polymerases, enzymes that act to copy a DNA or RNA template into a new RNA strand through processes known as transcription or RNA replication, respectively. 

Chromosome

A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.

Chromosomes vary widely between different organisms. The DNA molecule may be circular or linear, and can be composed of 100,000 to 10,000,000,000 nucleotides in a long chain. Typically, eukaryotic cells (cells with nuclei) have large linear chromosomes and prokaryotic cells (cells without defined nuclei) have smaller circular chromosomes, although there are many exceptions to this rule. Also, cells may contain more than one type of chromosome; for example, mitochondria in most eukaryotes and chloroplasts in plants have their own small chromosomes.

In eukaryotes, nuclear chromosomes are packaged by proteins into a condensed structure called chromatin. This allows the very long DNA molecules to fit into the cell nucleus. The structure of chromosomes and chromatin varies through the cell cycle. Chromosomes are the essential unit for cellular division and must be replicated, divided, and passed successfully to their daughter cells so as to ensure the genetic diversity and survival of their progeny. Chromosomes may exist as either duplicated or unduplicated. Unduplicated chromosomes are single linear strands, whereas duplicated chromosomes (copied during synthesis phase) contain two copies joined by a centromere.