Polygenic Inheritance and Genetic Susceptibility Screening


The genetic contribution to most common diseases of adult life, as well as variation in human characteristics, involves the interaction of multiple factors (polygenic inheritance). The identification of these genetic factors is the focus of a major research effort, but translating the findings into useful individualized risk predictions will be difficult.

Keywords: polygenic; susceptibility; single nucleotide polymorphism; epistasis; screening

Figure 1.

Two possible models for the allelic architecture of genetic disease. These are illustrated as different distributions of genotype relative risk (GRR) in relation to the total number of alleles conferring that GRR across all genes and diseases. The oligogenic model (thin curve) accommodates a significant number of alleles with intermediate effects (‘oligogenes’: GRR 3–20), whereas in the dichotomous model (thick curve) their number is very small. Linkage analysis can confidently detect oligogenes (solid bar), but not polygenes. The GRRs conferred by alleles of some known susceptibility alleles are indicated. The genes, alleles and corresponding diseases are as follows: insulin (INS), VNTR class 1, type 1 diabetes; APOE, e4, Alzheimer disease at 60 years; breast cancer 1, early‐onset (BRCA1), various mutations, breast cancer by age 70 years; major histocompatibility complex, class II, DQ beta 1 (HLA‐DQB1) 0201, type 1 diabetes. (From Wilkie, .)

Figure 2.

Simplified representation of epistatic interaction between susceptibility alleles. (a) The two alleles are shown individually and contribute effect sizes a and b. (b) Possible types of genetic interaction are shown. This may give rise to additive (left) or multiplicative (right) effects. Alternatively, the overall effect may be unaltered from one of the individual effects (center). Note that if effect a is protective, overall disease risk may actually be reduced below average, whereas identification of the susceptibility allele B alone could lead falsely to the conclusion that disease risk was increased. (From Wilkie, .)



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Web Links

Angiotensin I converting enzyme (peptidyl‐dipeptidase A) 1 (ACE); Locus ID: 1636. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1636

Apolipoprotein E (APOE); Locus ID: 348. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=348

Coagulation factor V (proaccelerin, labile factor) (F5); Locus ID: 2153. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2153

Hemochromatosis (HFE); Locus ID: 3077. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3077

Major histocompatibility complex, class I, B (HLA‐B); Locus ID: 3106. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3106

Peroxisome proliferative activated receptor, gamma (PPARG); Locus ID: 5468. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5468

Angiotensin I converting enzyme (peptidyl‐dipeptidase A) 1 (ACE); MIM number: 106180. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?106180

Apolipoprotein E (APOE); MIM number: 107741. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?107741

Coagulation factor V (proaccelerin, labile factor) (F5); MIM number: 227400. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?227400

Hemochromatosis (HFE); MIM number: 235200. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?235200

Major histocompatibility complex, class I, B (HLA‐B); MIM number: 142830. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?142830

Peroxisome proliferative activated receptor, gamma (PPARG); MIM number: 601487. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?601487

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How to Cite close
Wilkie, Andrew OM(Sep 2006) Polygenic Inheritance and Genetic Susceptibility Screening. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005638]