The genetic material of living organisms, DNA, is contained in chromosomes, which are present in the nuclei of cells. Chromosomes contain genes, which are the basic units of inheritance. Humans have 23 pairs of chromosomes: one member of each pair derived from the father and the other from the mother. Males have 22 pairs of autosomes and an X and a Y chromosome (the latter two are called sex chromosomes). Females have 22 pairs of autosomes and two X chromosomes. Ordinary body cells (somatic cells) contain the full complement of 23 pairs of chromosomes (referred to as the diploid number), whereas the mature germ cells—sperm and ova—contain only half the diploid number of chromosomes (referred to as the haploid number) that consists of 3 × 109 base pairs (bp) of DNA. Each of the genes occupies a specific position in a specific chromosome called the locus (plural loci). The two genes at each locus, one paternal and one maternal, are called alleles. The totality of all the genes is the genotype of the individual, and their manifestation is the phenotype.
Most eukaryotic (including human) genes are made up of sequences (exons) that code for amino acid sequences in proteins and noncoding intervening sequences (introns). Genes differ not only in the DNA sequences that specify the amino acids of the proteins they encode but also in their structures. A few human genes, such as histone genes, interferon genes, and mitochondrial genes, do not contain introns; some contain a considerable number of introns whose lengths vary from a few bases to several kilobases (kb; e.g., the dystrophin gene, DMD, mutations in which result in Duchenne’s and Becker’s muscular dystrophies, is 2400 kb long and contains 79 introns).
The 5′ end of the gene is marked by the translational start site (the ATG codon). Upstream from this are a number of noncoding sequences referred to as promoters; further upstream are a number of cis-acting regulatory elements of defined sequence (TATAAA and CCAAAT motifs), which play a role in constitutive gene expression, and enhancers, which respond to particular proteins in a tissue-specific manner by increasing transcription. At the 3′ end is the termination codon (e.g., TAA, TAG, TGA) and a poly-A tail.
The process by which genetic information in DNA is used to produce amino acids and proteins is called transcription. During this process, the entire unit of both introns and exons is transcribed into precursor messenger RNA (mRNA). The region of the precursor mRNA transcribed from the introns is then excised and removed and does not form the definitive mRNA. Precursor mRNA from the exons is spliced together to form the definitive mRNA, which specifies the primary structure of the gene product. The definitive mRNA is then transported to the cytoplasm, where protein synthesis occurs.
Mutations are permanent heritable changes that occur in the genetic material. They arise spontaneously and can be induced by exposure to radiation or chemical mutagens. When mutations arise or are induced in somatic cells, there is a very small probability that they will cause cancer, but somatic mutations are not transmitted to progeny. If mutations occur or are induced in germ cells, they can be transmitted to progeny and they may result in genetic (hereditary) diseases. Mutations are classified as dominant or recessive, depending on their effects on the phenotype (physical appearance of the organism). In the case of a dominant mutation, a single mutant allele inherited from either parent is sufficient to cause an altered phenotype; the organism has one mutant and one normal allele of the gene in question and is called a heterozygote with respect to that gene. In the case of a recessive mutation, two mutant alleles of the same gene—one from each parent—are required to produce a mutant phenotype; the organism is called a homozygote for the gene. In general, mutations in genes that code for structural proteins are dominant, and those in genes that code for enzymatic proteins are recessive.