Monogenic inheritance refers to genetic control of a phenotype or trait by a single gene. For a monogenic trait, mutations in one (dominant) or both (recessive) copies of the gene are sufficient for the trait to be expressed. Many traits are not determined so simply, and either involve the interaction of many genes with (multifactorial inheritance) or without (polygenic inheritance) environmental effects. Less commonly, the interaction of only two genes is required for expression of a phenotype, a mechanism referred to as digenic inheritance. In this situation, mutations in at least one copy of each gene are required for the expression of a phenotype. A growing number of human diseases with a digenic inheritance pattern are being described, a phenomenon that is likely to increase with more deoxyribonucleic acid (DNA) sequence data being generated through clinical-based exome and genome sequencing efforts.

Key Concepts:

• Traditional mendelian patterns of inheritance are controlled by mutations at a single genetic locus.
  
• Many human disorders are caused by more complex patterns of inheritance.
  
• Digenic inheritance refers to mutation on two genes interacting to cause a genetic phenotype or disease.
  
• Triallelic inheritance is a special case of digenic inheritance that requires homozygous mutations at one locus and heterozygous mutations at a second locus to express a phenotype.
  
• Digenic inheritance is probably best though of as being on a continuum that includes modifier effects of monogenic inheritance and polygenic or multifactorial inheritance.