INTRODUCTION

A mutation is a change in a genetic sequence. Mutations include changes as small as the substitution of a single DNA building block, or nucleotide base, with another nucleotide base. Meanwhile, larger mutations can affect many genes on a chromosome. Along with substitutions, mutations can also be caused by insertions, deletions, or duplication of DNA sequences.

TYPES OF MUTATIONS

Some mutations are hereditary because they are passed down to an offspring from a parent carrying a mutation through the germ line, meaning through an egg or sperm cell carrying the mutation. There are also nonhereditary mutations that occur in cells outside of the germ line, which are called somatic mutations. Mutations can be introduced due to mistakes made during DNA replication or due to exposure to mutagens, which are chemical and environmental agents that can introduce mutations in the DNA sequence, such as ultraviolet light. Some mutations do not result in changes in the amino acid sequence of the encoded protein and can be described as silent mutations. Other mutations result in abnormal protein products. Mutations can introduce new alleles into a population of organisms and increase the population's genetic variation. A change in the DNA sequence of a gene’s regulatory region can adversely affect the timing and availability of the gene’s protein and also lead to serious cellular malfunction. On the other hand, many mutations are silent, showing no obvious effect at the functional level. Some silent mutations are in the DNA between genes, or they are of a type that results in no significant amino acid changes.

Mutations are of several types. Changes within genes are called point mutations. The simplest kinds are changes to single base pairs, called base-pair substitutions. Many of these substitute an incorrect amino acid in the corresponding position in the encoded protein, and of these a large proportion result in altered protein function. Some base-pair substitutions produce a stop codon. Normally, when a stop codon occurs at the end of a gene, it stops protein synthesis, but, when it occurs in an abnormal position, it can result in a truncated and nonfunctional protein. Another type of simple change, the deletion or insertion of single base pairs, generally has a profound effect on the protein because the protein’s synthesis, which is carried out by the reading of triplet codons in a linear fashion from one end of the gene to the other, is thrown off. This change leads to a frame shift in reading the gene such that all amino acids are incorrect from the mutation onward. More-complex combinations of base substitutions, insertions, and deletions can also be observed in some mutant genes.

Mutations that span more than one gene are called chromosomal mutations because they affect the structure, function, and inheritance of whole DNA molecules microscopically visible in a coiled state as chromosomes. Often these chromosome mutations result from one or more coincident breaks in the DNA molecules of the genome (possibly from exposure to energetic radiation), followed in some cases by faulty rejoining. Some outcomes are large-scale deletions, duplications, inversions, and translocations. In a diploid species (a species, such as human beings, that has a double set of chromosomes in the nucleus of each cell), deletions and duplications alter gene balance and often result in abnormality. Inversions and translocations involve no loss or gain and are functionally normal unless a break occurs within a gene. However, at meiosis the specialized nuclear divisions that take place during the production of gametes—i.e., eggs and sperm), faulty pairing of an inverted or translocated chromosome set can result in gametes and hence progeny with duplications and deletions.

Loss or gain of whole chromosomes results in a condition called aneuploidy. One familiar result of aneuploidy is Down syndrome , a chromosomal disorder in which humans are born with an extra chromosome 21 (and hence bear three copies of that chromosome instead of the usual two). Another type of chromosome mutation is the gain or loss of whole chromosome sets. Gain of sets results in polyploidy —that is, the presence of three, four, or more chromosome sets instead of the usual two.Polyploidyhas been a significant force in the evolution of new species of plants and animals.

TYPES OF MUTATIONS AND THEIR IMPACTS

CLASS OF MUTATION	TYPE OF MUTATION	DESCRIPTION	HUMAN DISEASE LINKED TO THE MUTATION
POINT MUTATIONS	Substitution	One base is incorrectly added and replaces the other in the corresponding position	Sickle cell anemia
POINT MUTATIONS	Insertions	One or more extra nucleotides are inserted into replicating DNA, often resulting in a frameshift	One form of beta-thalassemia
POINT MUTATIONS	Deletions	One or more nucleotides is "skipped" during replication or otherwise excised, often resulting in a frameshift	Cystic fibrosis
CHROMOSOMAL MUTATIONS	Duplication	A region of a chromosome is repeated, resulting in an increase in dosage from the genes in that region	some types of cancers
CHROMOSOMAL MUTATIONS	Inversion	One region of a chromosome is flipped and reinserted	Opitz-Kaveggia syndrome
CHROMOSOMAL MUTATIONS	Deletions	A region of a chromosome is lost, resulting in the absence of all the genes in that area	Cri du chat syndrome
CHROMOSOMAL MUTATIONS	Translocations	A region from one chromosome is aberrantly attached to another chromosome	One form of leukemia
COPY NUMBER VARIATIONS	Gene amplification	The number of tandem copies of a locus is increased	Some forms of breast cancer
COPY NUMBER VARIATIONS	Expanding trinucleotide repeat	The normal number of repeated trinucleotide sequences is expanded	Fragile X syndrome, Huntington's disease