Genes

A gene is a unit of DNA that codes for a specific protein. The location of a gene on the chromosome is called the locus.

Genes consist of exons and introns. The exons contain the DNA code for the protein, while intervening introns, which make up most of the size of a gene, have an unknown function. The introns must be cut out and the exons spliced together in the mRNA before it leaves the nucleus.

The DNA sequence of a gene may vary among persons. Each variation is called an allele. If both alleles are the same, then the person is homozygous for the gene. If the alleles are different, then the person is a heterozygote.

If gene frequencies of alleles exceed 1% of persons in a population, then such alleles are called polymorphisms. For example, the major human blood grouping system, the ABO system, is determined by a single gene with three alleles: A, B, and O. Persons with type O are homozygotes (OO) because the presence of A or B determines the presence of A or B antigens on the red blood cells. Persons with blood group A can be either AA or AO and those with type B are either BB or BO. The rarest type is AB, in which case both antigens are present. This is an example of codominance. The frequency of these alleles varies around the world (the majority of Europeans are type A, Asians are mostly type B, while Mayans are exclusively type O).

The relationship between gene frequency and genotype is determined by the Hardy-Weinberg principle, which assumes that the genotype does not have an influence on marriage. Using this principle, one can roughly estimate the carrier rate. The rate of homozygotes should be the square of the gene frequency. Thus, for a disease such as cystic fibrosis, with 1 in 2500 Caucasians affected, the square root gives a gene frequency of 1 in 50, and a carrier rate double that, or 1 in 25.

Charles Darwin 's theory of natural selection is based upon selective advantage of genetic mutation introduced into a population, with advantageous genes increasing survival because of a selective advantage. Genes without selective advantage may become less frequent with time. The rapid increase in antibiotic resistant strains of micro-organisms is a good example of this phenomenon accelerated by modern medicine.

Differences in allelic frequencies in populations may be due to "founder effect" and to "genetic drift" over time. An example of the founder effect is the disease porphyria seen in the Afrikaaner population of South Africa. The Afrikaans community started with a small number of "founders" when the Dutch East India Company established a refreshment station at the Cape of Good Hope in 1652. The defective gene is believed to have been brought to South Africa in 1688 by Dutch orphan Ariaantje Adriaansse who was sent to the Cape to marry one of the early settlers, Gerrit Janz van Deventer. In a small, isolated population, the effect of random variation can become more pronounced, with genetic drift.

The alleles that are present represent the genotype of a person. The expression of the genotype leads to the phenotype, or what is clinically apparent in the person. Genetic heterogeneity refers to the appearance of a common phenotype for several genotypes. Pleiotropy refers to the appearance of multiple effects from one gene. The increase or decrease of gene function with various alleles is called dosage sensitivity.

Transcriptional genes, such as those of the HOX and PAX group, often act on other genes to activate or repress them. Mutations in the transcriptional genes may result in abnormalities that appear in multiple body sites.