Dominance and Recessivity

Abstract

The terms dominance and recessivity, originally codified by Gregor Mendel, are not strictly speaking intrinsic properties of genes or alleles but describe, in diploid organisms, the pattern of occurrence of a phenotypic trait with respect to the possible combinations of two alleles. If the trait is present in the heterozygote, it is said to be dominant or semidominant, and if it is present only in one of the homozygotes, it is recessive. In contemporary genetics, these terms are frequently used in a different but useful way to describe a property of the variant or mutant allele itself in relation to the normal, wild‐type state; this context is very helpful for understanding the molecular mechanisms by which mutations lead to disease. Practical applications include elucidation of genotype–phenotype relationships, structure–function studies of proteins and prediction of patterns of segregation of phenotypes to offspring in contexts such as selective breeding and genetic counselling.

Key Concepts

  • In comparing the traits (phenotypes) associated with alleles A and B in a diploid organism, the dominant phenotype is that observed in association with genotypes AA and AB, whereas the recessive phenotype is that observed in association with the BB genotype.
  • Semidominance of the phenotypes occurs when that associated with AB is intermediate between AA and BB.
  • A less formally correct, but operationally useful allele‐centric definition occurs when comparing the phenotypes associated with a rare variant allele to the normal (wild‐type) state. When heterozygotes appear phenotypically normal, the variant allele is described as recessive, but if they are abnormal, it is described as dominant.
  • Most (∼90%) variants of large phenotypic effect result in loss‐of‐function and the associated phenotype only manifests in the homozygous state (recessive to the wild‐type), because in heterozygotes, the function of the remaining wild‐type allele is sufficient for homeostasis.
  • Fewer than 10% of variants of large effect are associated with a phenotype in heterozygosity with wild type (i.e. dominant genetics). The reasons why the remaining wild‐type allele is unable to buffer the phenotype fall into distinct categories, depending on whether the functional consequence of the variant allele is to lose, gain or alter function.
  • Haploinsufficiency refers to the situation in which the remaining wild‐type allele (A) is unable to compensate fully for loss‐of‐function of the variant allele B, so that the phenotype in AB heterozygotes differs from normal.
  • Nonhaploinsuffciency or altered‐function mechanisms of dominance are diverse and specific to the context of the gene/protein involved. Common consequences include dominant‐negative activity and gain‐of‐function, which can include structural disruption and toxic cellular effects.

Keywords: dominance; semidominance; recessivity; haploinsufficiency; gain‐of‐function; loss‐of‐function; dominant‐negative; genotype–phenotype relationships

Figure 1. Mendel's experiment demonstrating the properties of dominance and recessivity. Cross‐pollination between pure‐bred lines of peas grown from round and wrinkled seeds gave rise only to round seeds (F1 generation). However, these F1 plants produced wrinkled seeds as well as round seeds when intercrossed, in a ratio of about three round to one wrinkled (F2 generation). Mendel explained this pattern by postulating that the phenotype was determined by the combination of factors R and r. The round is dominant over the wrinkled trait because the round trait is manifested in the heterozygote Rr. Conversely, wrinkled is recessive to round.
Figure 2. Dominance relationships between phenotypes and their relationship to genotype (denoted , or ). Classical Mendelism describes these relationships according to the phenotype (left column). A less formally correct, but practically useful classification according to allelic relationships (right column) is also frequently encountered. (a,b) Phenotypes corresponding to the different genotypes , and are indicated by filled rectangles of different tones. (c) In many dominantly inherited diseases, the phenotype associated with the homozygous mutant has not been observed because of the rarity of the genotype; hence it is not known whether allele is a true dominant or semidominant, with respect to .
Figure 3. Typical pedigrees showing autosomal dominant and autosomal recessive inheritance. Affected and unaffected individuals are denoted by filled and open symbols (square, male; circle, female), respectively. (a) Autosomal dominant inheritance of mutant allele . Transmission of the phenotype occurs vertically between generations. On average, 50% of the offspring of an affected individual are themselves affected, irrespective of sex. (b) Autosomal recessive inheritance of mutant allele . Consanguinity is frequent, as shown here (closely spaced parallel lines). Usually only a single sibship is affected, with previous and succeeding generations free of the disease. (c) If there is extensive inbreeding or the recessive mutant allele is very common, pseudodominant inheritance may occur.
Figure 4. Relationship between protein level and metabolic activity. Most proteins act at the asymptotic end of the activity curve. A 50% reduction in protein compared with the wild‐type level, caused by a heterozygous loss‐of‐function mutation, results in a reduction in activity of less than 10% (assumed to reflect the phenotype); complete loss of the protein abolishes activity. Hence the phenotype of the heterozygote resembles wild type and the mutation is recessive.
Figure 5. Common mechanism of dominant‐negative mutation. (a) Dimerisation mediated by the left half of the normal monomeric protein activates the function of the right half (shown as a change to shaded fill). (b) Heterozygous mutation that abolishes the activation domain but does not affect dimerisation will cause half of the normal protein to become sequestered into nonproductive signalling complexes.
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Further Reading

Agrawal AF and Whitlock MC (2011) Inferences about the distribution of dominance drawn from yeast gene knockout data. Genetics 187: 553–566.

Herskowitz I (1987) Functional inactivation of genes by dominant negative mutations. Nature 329: 219–222.

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Phadnis N and Fry JD (2005) Widespread correlations between dominance and homozygous effects of mutations: implications for theories of dominance. Genetics 171: 358–392.

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Web Links

Aquaporin 2 (collecting duct) (AQP2); MIM number: 107777. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?107777

GNAS complex locus (GNAS); MIM number: 139320. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?139320

Luteinizing hormone/choriogonadotropin receptor (LHCGR); MIM number: 152790. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?152790

Myocilin, trabecular meshwork inducible glucocorticoid response (MYOC); MIM number: 601652. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?601652

OMIM (Online Mendelian Inheritance in Man). A catalog of human genes and genetic disorders http://www.ncbi.nlm.nih.gov/Omim/

Prion protein (p27‐30) (Creutzfeldt–Jakob disease, Gerstmann‐Straussler‐Scheinker syndrome, fatal familial insomnia) (PRNP); MIM number: 176640. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?176640

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Wilkie, Andrew OM(Apr 2018) Dominance and Recessivity. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005475.pub2]