In somatic cell division, the genome is transmitted by mitosis, a nuclear division. In this process, each chromosome replicates into a pair of chromatids and the chromatids are pulled apart to produce two identical daughter cells. (Mitosis can take place in diploid or haploid cells.) At meiosis, which takes place in the sexual cycle in meiocytes, each homolog replicates to form a dyad of chromatids; then, the dyads pair to form a tetrad, which segregates at each of the two cell divisions. The result is four haploid cells, or gametes. Meiosis can take place only in a diploid cell; hence, haploid organisms unite to form a diploid meiocyte.

An easy way to remember the main events of meiosis, by using your fingers to represent chromosomes, is shown in Figure 2-33.

Genetic dissection of a biological property begins with a collection of mutants. Each mutant has to be tested to see if it is inherited as a single-gene change. The procedure followed is essentially unchanged from the time of Mendel, who performed the prototypic analysis of this type. The analysis is based on observing specific phenotypic ratios in the progeny of controlled crosses. In a typical case, a cross of A/A × a/a produces an F₁ that is all A/a. When the F₁ is selfed or intercrossed, a genotypic ratio of A/A : A/a : a/a is produced in the F₂. (At the phenotypic level, this ratio is A/– : a/a.) The three single-gene genotypes are homozygous dominant, heterozygous (monohybrid), and homozygous recessive. If an A/a individual is crossed with a/a (a testcross), a 1:1 ratio is produced in the progeny. The 1:1, 3:1, and 1:2:1 ratios stem from the principle of equal segregation, which is that the haploid products of meiosis from A/a will be A and a. The cellular basis of the equal segregation of alleles is the segregation of homologous chromosomes at meiosis. Haploid fungi can be used to show equal segregation at the level of a single meiosis (a 1:1 ratio in an ascus).

The molecular basis for chromatid production in meiosis is DNA replication. Segregation at meiosis can be observed directly at the molecular (DNA) level. The molecular force of segregation is the depolymerization and subsequent shortening of microtubules that are attached to the centromeres. Recessive mutations are generally in genes that are haplosufficient, whereas dominant mutations are often due to gene haploinsufficiency.

In many organisms, sex is determined chromosomally, and, typically, XX is female and XY is male. Genes on the X chromosome (X-linked genes) have no counterparts on the Y chromosome and show a single-gene inheritance pattern that differs in the two sexes, often resulting in different ratios in the male and female progeny.

Mendelian single-gene segregation is useful in identifying mutant alleles underlying many human disorders. Analyses of pedigrees can reveal autosomal or X-linked disorders of both dominant and recessive types. The logic of Mendelian genetics has to be used with caution, taking into account that human progeny sizes are small and phenotypic ratios are not necessarily typical of those expected from larger sample sizes. If a known single-gene disorder is present in a pedigree, Mendelian logic can be used to predict the likelihood of children inheriting the disease.