How Does Inheritance Work?

Our discussion here is restricted to sexually reproducing organisms where each gene in an individual is represented by two copies, called alleles—one on each chromosome pair. There may be more than two alleles, or variants, for a given gene in a population, but only two alleles can be found in an individual. Therefore, the probability that a particular allele will be inherited is 50:50, that is, alleles randomly and independently segregate into daughter cells, although there are some exceptions to this rule. The term diploid describes a state in which a cell has two sets of homologous chromosomes, or two chromosomes that are the same. The maturation of germ line stem cells into gametes requires the diploid number of each chromosome be reduced by half. Hence, gametes are said to be haploid—having only a single set of homologous chromosomes. This reduction is accomplished through a process called meiosis, where one chromosome in a diploid pair is sent to each daughter gamete. Human gametes, therefore, contain 23 chromosomes, half the number of somatic cells—all the other cells of the body. Because the chromosome in one pair separates independently of all other chromosomes, each new gamete has the potential for a totally new combination of chromosomes. In humans, the independent segregation of the 23 chromosomes can lead to as many as 16 to 17 million different combinations in one individual's gametes. Only one of these gametes will combine with one of the nearly 17 million possible combinations from the other parent, generating a staggering potential for individual variation. Yet, this is just the beginning. Even more variation is possible when you consider the recombination between sections of chromosomes during meiosis as well as the random mutation that can occur during DNA replication. With such a range of possibilities, it is amazing that siblings look so much alike!

Expression of Inherited Genes Gene expression, as reflected in an organism's phenotype, is based on conditions specific for each copy of a gene. As we just discussed, for every human gene there are two copies, and for every gene there can be several variants or alleles. If both alleles are the same, the gene is said to be homozygous. If the alleles are different, they are said to be heterozygous. For some alleles, their influence on phenotype takes precedence over all other alleles. For others, expression depends on whether the gene appears in the homozygous or heterozygous state. Still other phenotypic traits are a combination of several alleles from several different genes. Determining the allelic condition used to be accomplished solely through the analysis of pedigrees, much the way Mendel carried out his experiments on peas. However, this method can leave many questions unanswered, particularly for traits that are a result of the interaction between several different genes. Today, molecular genetic techniques exist that can assist researchers in tracking the transmission of traits by pinpointing the location of individual genes, identifying allelic variants, and identifying those traits that are caused by multiple genes.

The Nature of Alleles A dominant allele is an allele that is almost always expressed, even if only one copy is present. Dominant alleles express their phenotype even when paired with a different allele, that is, when heterozygous. In this case, the phenotype appears the same in both the heterozygous and homozygous states. Just how the dominant allele overshadows the other allele depends on the gene, but in some cases the dominant gene produces a gene product that the other allele does not. Well-known dominant alleles occur in the human genes for Huntington disease, a form of dwarfism called achondroplasia, and polydactylism (extra fingers and toes). On the other hand, a recessive allele will be expressed only if there are two identical copies of that allele, or for a male, if one copy is present on the X chromosome. The phenotype of a recessive allele is only seen when both alleles are the same. When an individual has one dominant allele and one recessive allele, the trait is not expressed because it is overshadowed by the dominant allele. The individual is said to be a carrier for that trait. Examples of recessive disorders in humans include sickle cell anemia, Tay-Sachs disease, and phenylketonuria (PKU). A particularly important category of genetic linkage has to do with the X and Y sex chromosomes. These chromosomes not only carry the genes that determine male and female traits, but also those for some other characteristics as well. Genes that are carried by either sex chromosome are said to be sex linked. Men normally have an X and a Y combination of sex chromosomes, whereas women have two X's. Because only men inherit Y chromosomes, they are the only ones to inherit Y-linked traits. Both men and women can have X-linked traits because both inherit X chromosomes. X-linked traits not related to feminine body characteristics are primarily expressed in the phenotype of men. This is because men have only one X chromosome. Subsequently, genes on that chromosome that do not code for gender are expressed in the male phenotype, even if they are recessive. In women, a recessive allele on one X chromosome is often masked in their phenotype by a dominant normal allele on the other. This explains why women are frequently carriers of X-linked traits but more rarely have them expressed in their own phenotypes. In humans, at least 320 genes are X-linked. These include the genes for hemophilia, red–green color blindness, and congenital night blindness. There are at least a dozen Y-linked genes, in addition to those that code for masculine physical traits. It is now known that one of the X chromosomes in the cells of human females is completely, or mostly, inactivated early in embryonic life. This is a normal self-preservation action to prevent a potentially harmful double dose of genes. Recent research points to the "Xist" gene on the X chromosome as being responsible for a sequence of events that silences one of the X chromosomes in women. The inactivated X chromosomes become highly compacted structures known as Barr bodies. The presence of Barr bodies has been used at international sport competitions as a test to determine whether an athlete is a male or a female.