Locus heterogeneity

Locus heterogeneity may have major implications for a number of human diseases. For instance, it has been associated with retinitis pigmentosa, hypertrophic cardiomyopathy, osteogenesis imperfecta, familial hypercholesterolemia, and hearing loss. Heterogenous loci involved in formation of the same phenotype often contribute to similar biological pathways. 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.

The detection of causal genes for diseases impacted by locus heterogeneity is difficult with genetic analysis methods such as linkage analysis and genome sequencing. 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. Existing techniques have been modified and new techniques have been developed to overcome these challenges.

Retinitis pigmentosa

Retinitis pigmentosa is a condition that causes damage to the light-sensitive cells of the retina. There have been over 60 genes identified whose mutations independently cause retinitis pigmentosa, and these can be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern. Examples of such genes include the rhodopsin gene (RHO), the gene encoding for retinitis pigmentosa GTPase regulator (RGPR), and the gene encoding retinitis pigmentosa 2 protein (RP2).