Non-Mendelian inheritance patterns of monogenic diseases
- Benjamin A Raby, MD, MPH
Benjamin A Raby, MD, MPH
- Section Editor — Genetics
- Associate Professor of Medicine
- Harvard Medical School
Disorders with a genetic basis can broadly be classified into two categories:
●Monogenic diseases — Monogenic diseases arise from a single gene and are recognized by their striking familial aggregation and classic Mendelian segregation patterns (eg, autosomal dominant, autosomal recessive, co-dominant, or sex-linked). These diseases are relatively rare.
●Complex diseases — Complex diseases are caused by the interaction of multiple genes with each other and with environmental factors. These diseases are common, and include cardiovascular disease, asthma, diabetes, inflammatory bowel disease, and cancer susceptibility. Single gene mutations can also cause some of these disorders (eg, BRCA1 and BRCA2 mutations in hereditary breast and ovarian cancers).
Despite the genetic basis of these patterns, many monogenic diseases appear to violate the laws of Mendelian inheritance. The less absolute the concordance between genotype and phenotype, the more difficult it can be to identify a disease as monogenic.
This topic reviews the non-Mendelian inheritance patterns that occur in monogenic disease processes and their causes. A table summarizes patterns of Mendelian and non-Mendelian inheritance (table 1).
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- PENETRANCE AND VARIABLE EXPRESSIVITY
- Variable expressivity
- Causes of incomplete penetrance and variable expressivity
- OTHER CAUSES OF NON-MENDELIAN INHERITANCE
- Parent-of-origin effects
- Digenic inheritance
- Triallelic inheritance
- Sex-limited expression
- Mitochondrial inheritance