Polygenic inheritance and micro/minisatellites.
While it has often been stated that the identification of the genes involved in complex polygenic traits may be extremely difficult, the principles learned in the past century about single gene-single disease inheritance may not be relevant to polygenic inheritance. A new paradigm specific to complex disorders may be needed. It is proposed that micro- and minisatellite polymorphisms play a role in the expression of many genes. As a result, these genes exist in the population with many functional alleleomorphic variants. While each variant has only a modest effect on a given phenotype, because the variants are common, and most quantitative traits are controlled by a number of genes, there is a reasonable probability that an individual will inherit a threshold number of functional variants beyond which there is an appreciable effect on the phenotype. Twelve different aspects of such a new model for complex inheritance, some corollary implications, and three examples of its immediate application, are presented with the hope that the model may allow an acceleration of the identification of the genes involved in complex polygenic disorders.
Comings
D E
DE
Department of Medical Genetics, City of Hope Medical Center, Duarte, CA 91010, USA. dcomings@mindspring.com
D004247:DNA / Q000235:genetics; D005796:Genes; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D001523:Mental Disorders / Q000235:genetics*; D018895:Microsatellite Repeats; D018598:Minisatellite Repeats; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011618:Psychotic Disorders / Q000235:genetics*; D018911:Trinucleotide Repeats
D004247:DNA