Oligogenic disease

Jon F. Robinson, Elias Nicholas Katsanis*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

11 Scopus citations


One of the primary goals of human and medical genetics is to assign predictive value to the genotype - that is to say, to use genetic information to assist in the diagnosis and management of disease. Recent work, originating primarily from disorders thought to be traditionally inherited in a Mendelian fashion, have blurred the boundaries between allele causality in monogenic and complex disease. Studies on genetic variation in disease are now revealing that essentially no disorder is transmitted solely in a Mendelian fashion; rather there are always multiple genetic and environmental factors that cause or modulate a disease phenotype. The focus of this chapter, oligogenic disorders, a term describing diseases caused by, or modulated by, a few genes, can provide a conceptual bridge between diseases classically considered monogenic and the poorly understood polygenic or complex disorders. The inheritance of alleles generally follows Mendelian laws of segregation and independent assortment. However, this axiom does not necessarily hold true when the segregation of disease traits is considered. Mendelian inheritance is founded on the notion that a trait (not exclusively a disease phenotype) is transmitted through a single locus; however, even in the most classic monogenic disorders the 1:1 or 3:1 Mendelian ratio of dominant to recessive phenotypes, respectively, cannot explain the breadth of phenotypic variation found in a clinical setting. Although environment also plays a part, new research is showing that a large amount of the pheno-typic variation in Mendelian disorders is due to genetic interaction of several genes (Nat Rev Genet 3:779-789, 2002). In that context, most, if not all, disorders should be considered multifactorial; and the main reason they are Mendelized is that the majority of the phenotype can be attributed to variation/mutations at a single locus.

Original languageEnglish (US)
Title of host publicationVogel and Motulsky's Human Genetics
Subtitle of host publicationProblems and Approaches (Fourth Edition)
PublisherSpringer-Verlag Berlin Heidelberg
Number of pages20
ISBN (Electronic)9783540376545
ISBN (Print)9783540376538
StatePublished - Jan 1 2010

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Oligogenic disease'. Together they form a unique fingerprint.

Cite this