Mendelian and Complex Disorders

Geneticists typically classify genetic disorders into two main categories: Mendelian and complex disorders. Mendelian disorders, such as sickle-cell disease, cystic fibrosis, and Duchenne muscular dystrophy, are usually rare in the general population. These disorders have predictable, recognizable inheritance patterns (such as autosomal dominant and X-linked recessive), and variations in a single gene are sufficient to cause expression of the disorder. Furthermore, only individuals who carry a mutation in the causative gene are at risk for expressing the disorder.

In contrast, complex disorders, such as cardiovascular disease, diabetes, cancers, and psychiatric disorders, are common in the general population. In these disorders, genetics plays a significant role, but the biology of the disease is due to a tangled web of genetic and environmental interactions. Consequently, complex disorders generally do not display the distinct inheritance patterns seen in Mendelian disorders.

While the genetic variation at a single gene may contribute to the overall risk of developing a disease, it is not expected to be sufficient for expression of the disease. A well-known example of this is the association between Alzheimer's disease and the APOE gene. Individuals who carry the "4" allele of the APOE gene have a higher risk and earlier age-of-onset for Alzheimer's disease than those with other alleles. Furthermore, this association is dose-dependent. Individuals who have two copies of APOE-4 are at greater risk for developing Alzheimer's disease than individuals who carry one copy of APOE-4 and one copy of a different allele.

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