Locus heterogeneity occurs when mutations at multiple genomic loci are capable of producing the same phenotype (ie. a single trait, pattern of traits, or disorder), and each individual mutation is sufficient to cause the specific phenotype independently.[1] Locus heterogeneity should not be confused with allelic heterogeneity, in which a single phenotype can be produced by multiple mutations, all of which are at the same locus on a chromosome.[1] Likewise, it should not be confused with phenotypic heterogeneity, in which different phenotypes arise among organisms with identical genotypes and environmental conditions.[2] Locus heterogeneity and allelic heterogeneity are the two components of genetic heterogeneity.[3]
Locus heterogeneity may have major implications for a number of human diseases. For instance, it has been associated with retinitis pigmentosa,[4]hypertrophic cardiomyopathy,[5]osteogenesis imperfecta,[6]familial hypercholesterolemia,[7] and hearing loss.[8] Heterogenous loci involved in formation of the same phenotype often contribute to similar biological pathways.[1] The role and degree of locus heterogeneity is an important consideration in understanding disease phenotypes and in the development of therapeutic treatment for these diseases.[1]
The detection of causal genes for diseases impacted by locus heterogeneity is difficult with genetic analysis methods such as linkage analysis and genome sequencing.[9] These methods rely on comparison of affected family members, but when different family members have different disease-causing genes, such genes may not be accurately identified.[9] Existing techniques have been modified and new techniques have been developed to overcome these challenges.[9][10][11]
