Genetics is the branch of biology that studies heredity and variation in organisms. It is important because it provides an understanding of what makes us the very person we are! By looking at genes and how they are inherited, we have made an immense progress in areas as diverse as evolution, developmental biology, taxonomy, ecology, and medicine!

Life is characterized by tremendous diversity, diversity in everything – morphology, physiology, and behavior in the life forms that inhabit this planet. In spite of this astonishingly huge diversity, the basic coding instructions are always written in the same language – the language of nucleic acids, irrespective of the shape, size or structure of the organism – irrespective of the fact whether it’s a plant or an insect or a virus! The basic genetic information is always encoded in the form of nucleic acids which may be deoxyribonucleic acids (DNA) or ribonucleic acid (RNA).

The study of DNA structure stretches back from 100 years but the currently accepted model of double helical structure was given by Watson & Crick in 1953. DNA, which is predominantly the major genetic component in most of the life forms, with its double stranded spiral is amongst the most elegant & incredibly stable of all biological molecules.

In the early 1920’s, P.A. Levene studied the underlying chemistry of DNA and discovered that DNA is a chain of large number of linked, repeating units, called deoxyribonucleotides. In turn each deoxyribonucleotide consists of a sugar, a phosphate molecule and a nitrogenous base all linked by covalent bonds. The nitrogenous base can be categorized into 2 types depending on the chemical structure: a Purine or a Pyrimidine. The standard Purines which are present in DNA are adenine (A) and guanine (G) and the standard Pyrimidines present in DNA are Thymine (T) and Cytosine (C).

So, depending on the type of nitrogenous base, there are four types of deoxynucleotides in the DNA:
adenine-deoxyribosephosphate (dAMP),
guanine-deoxyribosephosphate (dGMP),
cytosine-deoxyribosephosphate (dCMP)
thymine-deoxyribosephosphate (dTMP).

These four nucleotides are repeated in a string to make up what is known as a deoxyribonucleic acid (DNA) stand. The only difference between a DNA stand and an RNA stand is the presence of an additional oxygen molecule in the ribophosphates that that make up ribonucleic acid or an RNA.

Although only four types of base pairs are involved in formation of DNA, these base pairs may occur in any sequence. Finally, it is the pattern of arrangement of these nucleotides in a sequence that is of major significance.

An important characteristic of a nucleic acid strand is its direction. At one end, phosphate group is attached to the 5’-carbon atom of sugar in the nucleotide. This end is therefore called as 5’ end. The other end of strand is called as 3’ end which has OH group attached to 3’ carbon of sugar. This is important because this sequence information is always read from a 5’ towards the 3’ direction for functional purposes.
Chromosomes! What’s that!
The DNA, in its linear form is so long that it would map seven seas and may still not end! Obviously, there has to be some sort of packaging so that such a long molecule can be accommodated inside a microscopic entity by the name of cell! So, DNA is arranged with the help of several histone & non-histone structural proteins in a dynamically rearranging entity called Chromatin.

This organization is so that it allows structural compactness which is dynamically accessible to various proteins that read the inherent genetic information for making various effecter molecules – RNA and proteins.

What we call chromosome is a special arrangement of each DNA molecule at a specific stage during cell cycle. The benefit of studying chromosomes is that it represents a structure where every individual DNA molecule can be identified and studied for any large-scale anomalies.

It is important to realize that DNA, for most of the time, exists as an entangled thread like Chromatin organization and not in the form of Chromosomes. The chromosomal stage occurs only during cell division. However, each DNA molecule is named after its chromosome number as its unique identifier and is called “a chromosome” irrespective of its organization state.

There are 46 chromosomes in every cell of human body, except RBCs, megakaryotic liver cells, germ cells – sperm & ovum, & some other cells where this number varies. In other cells, this number 46 is comprised of 22 pairs of autosomes (44) and two copies of sex chromosomes – X and Y (XX in females & XY in males).
What the heck are Genes then!
Chemically speaking, a stretch of DNA with a particular sequence of nucleotides that code for a functional entity – an RNA or a polypeptide, along with various regulatory regions – again in the form of a particular sequence of nucleotides, is called a Gene.

Biologically speaking, a gene may be defined as the fundamental unit of heredity that encodes a genetic characteristic or trait. “Fundamental unit of heredity” refers to the smallest functional unit that is inherited by an offspring from its parent(s).

Genes specify a characteristic. But that character or trait may exist in multiple forms, for instance, a gene may code for eye color but the eye color (trait) may be black or brown or blue or green – i.e. multiple variants of a trait. Now these multiple variants are due to slight changes in nucleotide sequence of that gene forming genetic variants called Alleles. Alleles are nothing but slightly modified version of a gene, each coding for a unique variant of a given trait i.e. one allele may code for black color while other may code for blue.

These genes have been mapped by identifying their position on the chromosome and various regions on the chromosomes have been assigned numbers.

Each chromosome has a different set of genes. As there are 22 pairs of autosomes i.e. 2 copies of each of the 22 non-sex chromosomes in most of the cells, each set of genes in every autosome is represented twice – one copy from each parent. So, for each gene at a give locus in a pair of homologous chromosomes, there are 2 alleles which may or may not be same. These two particular alleles present at specified loci are referred to as Genotype.

The overall character or function represented by a gene depends on interaction between these 2 allelic copies. However, the final expressed or observable structural and functional traits depend on interaction of these alleles with alleles at other loci (other genes) and also with the environment. For instance, if there were a hypothetical gene for Coolness quotient, in simplest case, genotypes CC, Cc and cc would have represented phenotypes “Damn Cool”, “Average dude!”, and a “Silly boy – go get your hair combed” phenotypes! Of course, these relationships wouldn’t be so linear in more complicated situations if the gene for coolness is also affected by other genes and environmental interactions.

What we call Haplotype is a combination of alleles, for different genes, that are located closely together on the same chromosome and that tend to be inherited together.

Introduction to Mutations
Nature has very carefully selected our genetic material. The whole idea behind a genetic material is something which can store and transmit information while being remarkably stable. However, a primitive life form would have never evolved to more complex life forms had its genetic material never changed! So, the idea behind stability is not rigidity but a dynamic yet integrative flexibility.

Having said that, the genetic material is constantly exposed to various forces (more on that soon!) that may lead to various degrees of changes in the genetic code. Any sudden, relatively stable, discontinuous and inheritable change in the genotype of an organism is called a Mutation. Mutations occur frequently in nature – Why? Simply because nature is full of agents that may alter our genetic code – like solar UV radiations & radon gases!

If the changes are not lethal to the cell, they are copied and passed into new all the cells by cell division and if the changes are lethal, the affected cells die. In case the changes are passed on to future generations, if they are beneficial in some way, they tend to persist but if they confer no advantage, they lost over a period of time!

Types of Mutations:
Mutations can be categorized in several ways, on the basis of different criteria. Broadly, all of the mutations can be classified as somatic or germinal mutations according to the nature of cells affected by them.
i.Somatic Mutations: These are the genetic alternations in the somatic cells. These mutations are only transmitted to the cells formed from the mutated cell by division. In case the affected cell is a terminally differentiated cell, the mutations are not propagated. However, if they occur in precursor cells, they often show themselves as a patch of abnormal tissue. These mutations are not passed on to the offspring and disappear with the death of the affected cells. Somatic mutations have little genetic and evolutionary significance.

ii.Germinal Mutations: These are the genetic changes in the gametes – sperms and ova, which are transmitted to the offspring. If the germinal mutations are recessive, they are masked by normal dominant alleles and the traits of the offspring are not altered. If a mutation is dominant, a particular trait may express in an altered form in the offspring. Being inheritable, germinal mutations are of great genetic and evolutionary significance.

All mutations, whether somatic or germinal, can be classified as either Chromosomal mutations or small scale mutations in the genes. Chromosomal mutations are the large scale alternations in the chromosomal structure that are observable under microscope. These may involve structural modification in the chromosomes or a change in their number.

Each species has a characteristic number of chromosomes. The gametes having a single set of chromosomes are called haploid (n). All other cells having 2 sets of chromosomes are called diploid (2n). Any variation in the chromosome number is referred to as a change in ploidy which may lead to certain serious phenotypic variations.

This variation may occur in the number of whole sets of chromosomes (euploidy) or may involve addition or deletion of one or more chromosomes i.e. a part of the complete set (aneuploidy). Euploidy occurs naturally in certain liver cells but as an induced mutation, it is very rare. On the other hand, Aneuploidy is more common and is of great clinical significance. Cases of Down syndrome, Klinefelter Syndrome etc. are examples of aneuploidy.

There may also be structural or morphological modifications in the chromosomes. Structural modifications may be:

i.Intra-chromosomal modifications: These structural changes affect single chromosome and may occur in following ways:
a)Deletion: A segment of chromosome gets separated and lost.
Inversion: A segment of chromosome breaks and rejoins the same chromosome in an inverted position.
Duplication: A segment of chromosome duplicates and joins the same chromosome.

ii.Inter-chromosomal modifications: These are the changes that affect two chromosomes simultaneously and may occur in following ways:
a)Translocation: It refers to an exchange of a chromosomal segment from one chromosome to another.
Duplication: It refers to duplication of a chromosomal segment which may attach to a different chromosome.

As compared to chromosomal mutations, the mutations in genes are on a far smaller scale. There are four types of gene mutations according to the type of changes in the base sequence:

i.Substitution: In this type of mutations, one or more bases are substituted with some other bases. These are of two types:
a)Transitions: These are the mutations in which a purine is replaced by another purine (i.e. A is substituted by G & vice-versa) or a pyrimidine is replaced by another pyrimidine (i.e. C is replaced by T & vice-versa).
Transversion: These are the mutations in which a purine is replaced by a pyrimidine (i.e. A or G is substituted by T or C) & vice-versa.

i.
ii.Deletion: In this case, one or more bases are lost from a DNA segment.
Insertion: In this case, one or more bases are inserted into a DNA segment.
Duplication: In these cases, there is duplication of an entire gene that may exist in the form of tandem repeats in the DNA.

Mutations may also be categorized according to the direction in which they occur. A mutation from the wild phenotype to a new phenotype is called forward mutation whereas a mutation that reverts to its original condition in another generation is called a reverse mutation!
Sources of Mutations:
Mutations may arise spontaneously due to certain intracellular factors or be induced by various environmental factors. The factors that cause mutations are known as mutagenic agents.

Mutations may occur spontaneously in nature. These mutations arise generally because of errors during DNA replication or because of certain intra-cellular mutagens like peroxides, nitrous oxide etc. The frequency of these mutations is relatively low.

Mutations may also arise because of any of the following major mutagenic agents:

i.Radiations: Ionizing radiations including x-rays, gamma rays, alpha rays, UV rays etc. may cause disruptive changes in the DNA.

ii.Chemicals: Certain chemicals react with the bases of DNA and change them into abnormal bases. For instance, radon gas – a radioactive gas formed by the disintegration of radium which occurs naturally (especially in areas over granite), is a mutagen. Some chemicals resemble the chemical structure of standard bases of DNA and therefore incorporated by mistake in the DNA during replication. Such mutagens are called base analogues, example, 5-bromo-uracil which is similar to normal pyrimidine.