Many of the terms used in this section are defined in the Genetics Glossary in the appendix. See also the section Terminology: Hereditary, Genetic, Familial, Congenital later in this chapter.
Dominant Versus Recessive Inheritance
The terms dominant and recessive were first used by Gregor Mendel. In classical genetics, a dominant gene is always expressed with similar phenotype, whether the mutant gene is present in a homozygous or heterozygous state. Stated simply, a dominant gene is expressed when present in only a single copy. A gene is called recessive if its expression is masked by a normal allele or, more precisely, if it is expressed only in the homozygote (or compound heterozygote) state when both alleles at a specific locus are mutant.
A trait is the consequence of the gene’s action. It is the trait, or phenotypic expression of the gene at a clinical level, rather than the gene itself, that is dominant or recessive. A trait is recessive if its expression is suppressed by the presence of a normal gene (as in galactosemia) and dominant if it is apparently unaffected by a single copy of the normal allele (as in Marfan syndrome). If the alleles are different and yet are both manifested in the phenotype, they are said to be codominant. Examples of phenotypes with codominant inheritance patterns include the ABO blood types, HLA types, and hemoglobin variants (as involved in sickle cell disease).
As a result of epigenetic factors, a gene may have a greater or lesser effect on the individual or an organ, and therefore the trait may be more or less apparent. Thus, the designation of a trait as either dominant or recessive depends on the testing method used. Although classically a dominant gene has the same phenotype when the mutant allele is present in either the heterozygous or the homozygous state, most dominant medical diseases act more like codominant diseases, in which individuals who are homozygous for a mutant allele or who harbor 2 mutant alleles will have more severe expression than will those with only 1 mutant allele.
In experiments, the biochemical mechanisms of dominant hereditary diseases appear different from those of recessive disorders. Recessive traits usually result from enzyme deficiencies caused by mutations of the gene specifying the affected enzyme. The altered enzyme often can be shown to be structurally abnormal or unstable. Heterozygotes usually have approximately 50% of normal enzyme activity but are clinically unaffected, implying that half of the normal enzyme activity is compatible with near-normal function. If adequate biochemical testing can be performed and the specific enzyme isolated, the reduced enzyme activity can be quantified and the heterozygous genetic state inferred. Thus, clinically unaffected heterozygotes can be detected for such disorders as homocystinuria (decrease in cystathionine β-synthase), galactokinase deficiency (low blood galactokinase activity), classic galactosemia (galactose-1-phosphate uridyltransferase deficiency), gyrate atrophy of the choroid and retina (decreased ornithine aminotransferase), and Tay-Sachs disease (decreased hexosaminidase A). Table 6-1 outlines known enzyme disorders with ocular manifestations.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.