Polygenic Inheritance and Genetic Susceptibility Screening

Andrew OM Wilkie, University of Oxford, Oxford, UK

Published online: September 2006

DOI: 10.1002/9780470015902.a0005638

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, 2001.)
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, 2001.)
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 Web Links
    ePath Angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 (ACE); Locus ID: 1636. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1636
    ePath Apolipoprotein E (APOE); Locus ID: 348. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=348
    ePath Coagulation factor V (proaccelerin, labile factor) (F5); Locus ID: 2153. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2153
    ePath Hemochromatosis (HFE); Locus ID: 3077. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3077
    ePath Major histocompatibility complex, class I, B (HLA-B); Locus ID: 3106. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3106
    ePath Peroxisome proliferative activated receptor, gamma (PPARG); Locus ID: 5468. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5468
    ePath Angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 (ACE); MIM number: 106180. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?106180
    ePath Apolipoprotein E (APOE); MIM number: 107741. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?107741
    ePath Coagulation factor V (proaccelerin, labile factor) (F5); MIM number: 227400. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?227400
    ePath Hemochromatosis (HFE); MIM number: 235200. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?235200
    ePath Major histocompatibility complex, class I, B (HLA-B); MIM number: 142830. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?142830
    ePath Peroxisome proliferative activated receptor, gamma (PPARG); MIM number: 601487. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601487

Related Sub-Topics:

Molecular Genetics of Common and Complex Disease | Techniques and Tools in Clinical Genetics | Health Care
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Article Title: Polygenic Inheritance and Genetic Susceptibility Screening
 
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]