Linkage Analysis of Genetic Disorders

Genetic disorders follow a classic Mendelian dominant or recessive single-locus pattern of inheritance or a complex genetic pattern (multiple genes and environmental influences). In general, the complexity arises when the simple correspondence between genotype and phenotype is not one to one due to possible misclassification of phenotype, incomplete and age-dependent penetrance, phenocopies, genetic heterogeneity and/or oligogenic inheritance. Errors in diagnosis could be the result of variable expression of a disease with mildly affected individuals being misdiagnosed as unaffected. In the presence of incomplete or age-dependent penetrance, an individual who inherits a predisposing disease allele may not manifest the disease at all or the chance of manifesting the disease may depend on his or her age. On the other hand, phenocopies are individuals who do not inherit the disease allele but have the disease in question, probably caused by environmental factors and/or other genes. Genetic heterogeneity is a situation where mutations in any one of several genes may result in identical phenotype. Oligogenic inheritance requires the simultaneous presence of mutations in multiple genes.