The basic laws of inheritance are important in understanding patterns of disease transmission. The inheritance patterns of single gene diseases are often referred to as Mendelian since Gregor Mendel first observed the different patterns of gene segregation for selected traits in garden peas and was able to determine probabilities of recurrence of a trait for subsequent generations. If a family is affected by a disease, an accurate family history will be important to establish a pattern of transmission. In addition, a family history can even help to exclude genetic diseases, particularly for common diseases where behavior and environment play strong roles.

Most genes have one or more versions due to mutations or polymorphisms referred to as alleles. Individuals may carry a ‘normal’ allele and/or a ‘disease’ or ‘rare’ allele depending on the impact of the mutation/polymorphism (e.g., disease or neutral) and the population frequency of the allele. Single-gene diseases are usually inherited in one of several patterns depending on the location of the gene and whether one or two normal copies of the gene are needed for the disease phenotype to manifest.

The expression of the mutated allele with respect to the normal allele can be characterized as dominant, co-dominant, or recessive. There are five basic modes of inheritance for single-gene diseases: autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and mitochondrial.

Genetic heterogeneity is a common phenomenon with both single-gene diseases and complex multi-factorial diseases. It should not be surprising that multiple affected family members may experience different levels of disease severity and outcomes. This effect may be due to other genes influencing the disease phenotype or different mutations in the same gene resulting in similar, but not identical phenotypes. Some excellent resources for information about single-gene diseases is the Online Mendelian Inheritance in Man (OMIM; http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM) and GeneTests/GeneClinics (http://www.genetests.org).