They involve either inversions (simple reversals of an internal segment of a chromosome) or translocations (transfer of a segment of a chromosome  to a new location). Translocations can occur within or between chromosomes, the latter often reciprocally. Even when not directly deleterious, rearrangements lead to anomalies of genetic recombination; a common secondary consequence in humans is sterility.

Addition mutations are of two types, duplications and insertions. Duplications usually consist of tandem repeats of a segment of a chromosome, and may range from innocuous to lethal depending upon their location and extent. Insertions occur through the movement of special DNA sequences (transposons) that range from hundreds to thousands of DNA base pairs in length.

Gene mutations affect only a single gene and consist of intragenic chromosomal mutations, additions or deletions of one or a few base pairs, base-pair substitutions (point mutations), and complex mutations comprising simultaneously arising clusters of any of the above. The severity of a gene mutation depends on its individual nature and on the importance of the affected gene, and can range from innocuous to lethal.
Base-pair substitutions are divided into two groups called transitions and transitions. In transitions, such as A.T. G. C, the purine pyrimidine orientation is maintained; in transversions, such as A.T.C.G, this orientation is reversed. (Here the DNA bases are denoted by A = adenine, T = thymine, G = guanine, and C = cytosine, where A and G are purines and T and C are pyrimidines; the dots indicate hydrogen bonding between bases.)

Because the genetic code employs consecutive sets of three DNA base pairs to specify consecutive amino acids in proteins, the addition or deletion of multiples of three base pairs leads to the addition or deletion of one or more amino acids. However, the addition or deletion of one or two base pairs (or any nonmultiple of three) shifts the reading frame, so that everything from that point onward is read out of its normal  frame, with drastic consequences for that particular gene. These occurrences are called frameshift mutations.

Forward and Reverse Mutation
Mutations from a normally functioning reference gene, chromosome, or organism to a mutant condition are called forward mutations. Their reversal by a new mutation that restores the original DNA sequence is called back mutation, or reversion. In addition, new mutations at a site distinct from a forward mutation can sometimes restore the nonmutant phenotype; these are called suppressor mutations. For instance, a base-pair addition in a protein-encoding sequence can sometimes be suppressed by the nearby deletion of a different base pair: the reading frame is restored, and the organism may no longer appear mutant if the associated amino acid changes are innocuous and the protein therefore functions normally.

Soma and germ line
In sexually reproducing multicellular animals, a mutation that arises in a somatic (body) cell cannot be passed to future generations, whereas a germ-line mutation can. Even though somatic mutations cannot harm future generations, they can be important to the individual that carries the mutant cell. They can be deadly (as by leading to cancer) or beneficial (as by generating new antibody molecules).

Scoring Mutations
The rarity and sporadic nature of mutations render their study in wild organisms (that is, those in nature) very difficult. Instead, mutagenesis is studied in specialized laboratory organisms, among which microorganisms are favored because the ease of growing large populations (such as 109) overrides the low frequencies of mutants (such as 1 in 107 organisms). In the bacterial virus T4, the circular plaques formed by viral killing of a lawn of the bacterial host have a characteristic size and fuzzy edge. Visual screening readily detects, r mutants that make larger, sharp-edged plaques. Among these, the rIImutants have been widely studied because their rare revertants (and also recombinants) can be selected by growing on special bacterial hosts resistant to the parental rIIviruses

Among bacteria and yeasts, many biochemical traits have been used to score mutations. A frequent approach is first to obtain a mutant that requires for its growth a special nutrient, such as a vitamin or an amino acid. By growing the mutant population in a medium lacking the required growth factor, rare revertants to nutritional independence can be selected. For instance, the widely used Ames test for environmental mutagens uses mutants of the bacterium Salmonella typhimurium that require the amino acid histidine for growth, and the method tests for mutagens that can induce reversion.
In the fruit fly Drosophilamelanogaster, special chromosomes are used to score induced lethal mutations on the X chromosome. Because these mutations are recessive (their effect being masked in the presence of a nonmutated chromosome) and because the X chromosome is a sex chromosome, this system screens for sex-linked recessive lethals. It is the most efficient mutation-scoring system in a higher eukaryote.
Because of the difficulties of raising and examining mice by the tens of thousands under well-controlled conditions, mutation experiments are infrequently conducted with these or any other mammals. However, their chromosomal mutations can sometimes be scored by cytological (microscopal) analyses, and their gene mutations can be scored in a few systems, such as the specific-locus system in which mutations can be detected in any of seven specific genes determining, for the most part, coat-color traits. (A locus is the position of a gene on a chromosome.) The systematic study of mutation in humans is difficult for obvious reasons, and has amounted to little more than recording incidences and examining patterns of inheritance.
Although important mechanisms of mutagenesis undoubtedly remain to be discovered, many, and perhaps most, of the predominant mechanisms are now known, at least in outline. Mutations that alter the number of chromosomes in a cell usually result from the faulty distribution of chromosomes during mitotic or meiotic cell divisions. The fault probably often lies in the systems of spindle fibers that segregate daughter chromosomes into daughter cells; chemicals (such as colchicine) that interfere with such fibers induce aneuploidy at high frequencies.
The larger of these, and probably many of the smaller as well, can be formed by chromosome breakage followed by incorrect patterns of rejoining. Many agents, including ionizing radiations and numerous chemicals, can induce chromosome breaks. As might be expected from their topology, the frequency of chromosome mutations often corresponds to the square of the dose of mutagen, that is, as "two-hit" events (two breaks plus incorrect rejoining). The mechanism of efficient rejoining of broken chromosomes is not understood, but may involve base pairing between repeated DNA sequences in the chromosome. The frequency of repeated sequences is high in the chromosomes of higher organisms, and chromosomal mutations, particularly deletions, are also frequent relative to point mutations in these organisms. In addition to events triggered by breaks, however, deletions and duplications are triggered by anomalies of genetic recombination between similar but nonhomologous DNA sequences
These usually arise, not following random chromosome breaks, but through the intrinsic mobility of highly specialized DNA sequences. Called transposons, they have been found to be a major factor in spontaneous mutagenesis, because their transposition into a gene is very likely to inactivate that gene. They seem to play at most a minor role in induced mutagenesis. Transposons come in several types and sizes. Many carry repeated DNA sequences at their ends. Their mobility of often engendered by one or more of their own genes. For example, a DNA copy may be produced and then inserted elsewhere by a specialized recombination mechanism. Alternatively, the transposon may be transcribed into ribonucleic acid copied back into DNA by a reverse transcriptase, and then inserted.
This is a set of mutagenic mechanisms that proceeds through correct DNA base pairing in an incorrect (misaligned) context, generating deletions, duplications, and point mutations.
Consider two DNA sequences, identical or nearly so but separated by several to many base pairs. If the repeated sequences are sufficiently long (perhaps dozens to hundreds of base pairs) to mediate genetic recombination, then “unequal” recombination can occur, generating a duplication or a deletion or both (Fig. 1). Even if the repeated sequences are too short for ordinary recombination, they may still mediate anomalies of DNA metabolism that lead to duplications and deletions

Fig. l Formation of duplication and deletion mutations by aberrant recombination.

Fig 2 Schemes for mutagenesis by misalignments within a single chromosome:(a) between distant repeated sequences; and (b) within a redundant sequence. Continuous lines represent DNA sugar-phosphate backbones, and dots indicates base pairing via hydrogen bonds.

A. Double- Stranded DNA bearing short repeated sequences and a nearby strand break B. Enzymatic enlargement of break plus local meeting C. Out-of-register reannealing D. Gap-filling DNA synthesis E. Ordinary DNA replication F. Double-stranded DNA bearing a deletion (normal progeny chromosome not shown)	A. Double-stranded DNA bearing a redundant sequence and a strand break. B. 6A-T pairs C.Local melting followed by out-of-register reannealing D. Unpaired thymine E. Gap-filling DNA synthesis followed by ordinary DNA replication F. 7 A-T pairs G. Double-stranded DNA bearing an addition of one A-T base pair (normal progeny Chromosome not shown)

(Fig. 2): a Break occurs in one of the two DNA chains separate (melt) locally, and then the reform a double helix out of register (misanneal). Subsequent DNA synthesis then closes the gap, fixing the mutation in the chromosome. In the extreme example, the DNA sequence repeat lacks intervening bases, and the additions or duplication are of only one or a few bases (generating, if occurring within a  protein-coding sequence, frameshift mutations). If one of the component of a repeated DNA sequence is inverted with respect to the other (both end to end and top  strand to bottom strand in order to preserve the chemical polarity of DNA), the result is a DNA palindrome (a sequence that is the same when read in either direction). Just as direct repeats can mediate misalignments, so can palindromes, but with sometimes quite different consequences. For instance, during the transitory stages when DNA becomes single-stranded, as during replication, excision repair, and recombination, palindromic DNA sequences can fold back upon each other to form "hairpin" structures (Fig. 3). Such an anomaly can lead to a deletion, either because synthesis of the complementary strand passes by the hairpin or because the hairpin is recognized as an abnormal DNA structure, and excised. In practice, while the ends of deletions often fall in either repeated or palindromic sequences, they also often fall in regions which contain both elements a once, thus providing enhanced misalignment stability.
Palindromes  possess an additional property, not shared with direct repeats, that causes them to mediate the formation of point mutations. Consider a palindrome which is imperfect, the inverted repeats not being perfect complements. (Here the intervening bases between the palindromic elements are irrelevant.) If it assumes a hairpin structure, then its stem will encompass mispaired or nonpaired bases (Fig. 4). The repair systems that maintain the structural integrity of DNA by excising damaged, abnormal, or mispaired bases can then act upon this perfect stem, "correcting” one of its strands. The result can be base-pair substitutions, base additions or deletions, and complex mutations. (It should be noted that the mechanisms discussed here have been set in the hairpin context, but  may actually occur by topologically related misalignments at DNA replication forks.)
Fig 3 palindrome-mediated deletion mutagenesis. Color indicates palindromic sequences.

DNA Palindrome in linear Configuration

↓↑

DNA Palindrome in Hairpin Configuration

↓excision of one hairpin

and closure of the gap

↓ DNA

replication
One normal plus one deletion - mutant progeny

Fig 4 . Palindrome-mediated frameshift mutagenesis. Color indicates imperfectlu sequences.

quasipalindrome in linear configuration

↓DNA becomes locally

single - stranded and shifts to hairpin configuration

Hairpin configuration with extra base

swung out from stem

↓ removal of extra base

by6 aberrant DNA repair

↓ DNA synthesis

reforming linear configuration

mutant sequence deleted for one T. A base pair

The normal pairing between the DNA bases (A. T amd G.C) is shown in -Fig. 5aand b.DNA bases can also pair incorrectly, usually because of transient changes in base structure. An early mispairing proposal invoking base tautomers created by proton migration is shown in Fig. 5c. Structural studies now suggest mispairing via "wobble" configurations or ionized bases. Note, however, that the next round of pairing by these bases is likely to be normal, generating one mutant and on nonmutant progeny DNA double helix.

Fig. 5 Normal pairings and mispairings between the DNA bases (a) The normal adenine thymine base pair; hydrogen bonds are indicated by dotted lines and glycosidic bonds to the DNA backbone by heavy lines. (b) The normal guanine cytosine base pair. (c) An adenine cytosine mispair caused by proton migration in an adenine (arrow), leading to a transition mutation. (d) A guanine thymine mispair involving wobble pairing. (e) An adenine cytosine mispair involving both a protonated base and wobble pairing.

A. Adenine B. Thyrnine	A. Guanine B. Cytosine	A. Adenine B.Cytosine
A. Guanine B. Thymine	A. Adenine (protonated) B. Cytosine

In order to generate a transversion, either two purines or two pyrimidines must mispair. In their usual configurations, however, neither such pair approximates the normal dimensions of a DNA base pair. In practice, most transversions arise via purine purine mispairs; one example is shown in Fig. 6. In a normal base pair, the purines are in the anti configuration, which means that their hexagonal ring points toward the complementary pyrimidine. Occasionally, however, a purine (adenine in this example) rotates -180° around its glycosidic bond (the bond leading from the base to the sugar-­phosphate backbone) into the syn configuration, thus presenting a different part of itself for potential pairing via hydrogen bonds.
Fig. 6 A guanine adenine mispair involving rotation of the adenine around its glycosidic bond. The mispair leads to a transversion mutation.

A. Guanine (anti)
B. Adenine (syn)