Dominant Traits and Diseases

Abstract

The principles of genetic dominance and recessiveness established by Gregor Mendel in his experiments with garden peas equally apply to human genetic diseases. For dominant diseases, which affect approximately 1/70 individuals, the inheritance of one copy of the disease‐causing allele is sufficient to produce disease. Most commonly, an affected heterozygote mates with an unaffected homozygote, resulting in a recurrence risk of 50% for the offspring. In some cases, a parent transmits a de novo mutation to an offspring; the risk to subsequent offspring of this parent is not elevated above that of the general population. Incomplete penetrance, in which a carrier of the disease‐causing allele does not develop the disease phenotype, is a common feature of autosomal dominant diseases. Variable expression, in which genetic and/or nongenetic factors modify the severity of the phenotype, is another common feature of autosomal dominant diseases.

Key Concepts

  • Recurrence risks for autosomal dominant diseases are 50% for a carrier × unaffected mating and 75% for a carrier × carrier mating.
  • For autosomal dominant diseases resulting from a new mutation transmitted by a parent, the recurrence risk for siblings of the affected individual is the same as that of the general population, whereas the recurrence risk for the individual's offspring is typically 50%.
  • Incomplete penetrance, which is seen in familial retinoblastoma, familial breast/ovarian cancer and many other dominant diseases, occurs when a carrier of the disease‐causing allele does not manifest the disease phenotype.
  • Many dominant diseases are characterised by age‐dependent penetrance, in which the probability of manifesting the disease phenotype increases with age.
  • Several factors can influence the severity of expression of a dominant disease, including the location and type of disease‐causing allele, the effects of modifier loci and the effects of the nongenetic environment.
  • Many autosomal dominant diseases involve locus heterogeneity, in which mutations at different disease‐causing loci can cause the same disease phenotype.
  • Pleiotropy, as seen in Marfan syndrome and osteogenesis imperfecta, is a frequent feature of genetic diseases and describes the fact that a single disease‐causing allele can affect multiple aspects of the patient's phenotype.

Keywords: dominant inheritance; locus heterogeneity; penetrance; recurrence risk; variable expressivity

Figure 1. Outcomes of the mating of parents with the AA and aa genotypes.
Figure 2. Outcomes of the mating of parents with the Aa and aa genotypes. Affected genotypes among the offspring are shaded.
Figure 3. Outcomes of the mating of parents with the Aa and Aa genotypes. Affected genotypes among the offspring are shaded.
Figure 4. A pedigree illustrating the inheritance of brachydactyly, an autosomal dominant trait. Affected individuals are shown in green colour. Males are represented by squares, females are represented by circles.
Figure 5. A pedigree illustrating reduced penetrance of an autosomal dominant allele. Affected individuals are shown in green colour. The lightly shaded individual in generation II has the disease‐causing allele but does not develop the disease. Males are represented by squares, females are represented by circles.
Figure 6. A pedigree illustrating the phenomenon of anticipation (the age of each affected individual (green) is shown beneath the pedigree symbol). Males are represented by squares, females are represented by circles.
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Further Reading

Jorde LB, Carey JC and Bamshad MJ (2016) Medical Genetics, 5th edn. Philadelphia: Elsevier.

Korf BR and Irons MB (2013) Human Genetics and Genomics, 4th edn. New Jersey: Wiley‐Blackwell Publishing.

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Jorde, Lynn B(Nov 2017) Dominant Traits and Diseases. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001876.pub3]