Genetic Risk: Computation

Abstract

Despite the progress of molecular genetics and the resulting improved possibilities for precise risk classification in affected families, the principles of formal risk assessment continue to be of great importance as a decision‐making aid for a targeted molecular genetic analysis and an adequate interpretation of molecular findings. Assuming a genetic model, which is both the basis for risk assessment and the interpretation of molecular findings is of great importance. Even in the molecular era Bayesian theorem has to be applied in monogenetic diseases like Huntington disease, spinal muscular atrophy and Duchenne muscular dystrophy. Precise risk assessment in genetic counseling often deserves Bayesian risk calculation.

Key Concepts

  • Risk assessment in families with genetic diseases is of great importance in spite of improved molecular diagnostics.
  • Risk assessment is important for both the indication of molecular diagnostics and the interpretation of possible molecular findings.
  • The prerequisite for the risk assessment is the assumption of a specific genetic model.
  • Taking a larger number of variables (e.g. incomplete penetrance, spontaneous mutations and late onset) into account, risk calculation can significantly modify a priori risks.

Keywords: risk calculation; Bayes' theorem; Mendelian inheritance; genetic model; linked markers; penetrance; risk function

Figure 1. Autosomal inheritance with incomplete penetrance. Caesar and Doris are asking for an assessment of the risk of having an affected child.
Figure 2. Risk of being affected, for a child of the healthy offspring of an affected person with an autosomal dominant trait with incomplete penetrance.
Figure 3. Autosomal dominant inheritance with late onset. Ernst is asking for an assessment of his risk of being a heterozygote.
Figure 4. Autosomal recessive inheritance. Doris, the sister of an affected brother (Caesar), is asking for an assessment of her risk of having an affected child.
Figure 5. X‐linked recessive inheritance; DMD.
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References

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Further Reading

Bickeböller H and Fischer C (2007) Einführung in die Genetische Epidemiologie (Statistik und ihre Anwendungen). Heidelberg, Germany: Verlag: Springer.

Bridge PJ (1994) The Calculation of Genetic Risks. Baltimore, MD: Johns Hopkins University Press.

Lathrop GM and Lalouel JM (1984) Easy calculations of lod scores and genetic risks on small computers. American Journal of Human Genetics 36: 460–465.

Young ID (1991) Introduction to Risk Calculation in Genetic Counselling. Oxford, UK: Oxford University Press.

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How to Cite close
Grimm, Tiemo, Müller‐Myhsok, Bertram, and Zerres, Klaus(Oct 2017) Genetic Risk: Computation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005433.pub2]