Biology:Locus heterogeneity
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]
Retinitis pigmentosa
Retinitis pigmentosa is a condition that causes damage to the light-sensitive cells of the retina.[12] 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.[13] 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).[14]
See also
- Allelic heterogeneity
- List of cutaneous conditions caused by mutations in keratins
References
- ↑ 1.0 1.1 1.2 1.3 "Locus heterogeneity disease genes encode proteins with high interconnectivity in the human protein interaction network". Frontiers in Genetics 5: 434. 2014-12-09. doi:10.3389/fgene.2014.00434. PMID 25538735.
- ↑ "A functional perspective on phenotypic heterogeneity in microorganisms". Nature Reviews. Microbiology 13 (8): 497–508. August 2015. doi:10.1038/nrmicro3491. PMID 26145732.
- ↑ "NCI Dictionary of Genetics Terms" (in en). 2012-07-20. https://www.cancer.gov/publications/dictionaries/genetics-dictionary.
- ↑ "Genes and mutations causing retinitis pigmentosa". Clinical Genetics 84 (2): 132–41. August 2013. doi:10.1111/cge.12203. PMID 23701314.
- ↑ "Familial hypertrophic cardiomyopathy is a genetically heterogeneous disease". The Journal of Clinical Investigation 86 (3): 993–9. September 1990. doi:10.1172/JCI114802. PMID 1975599.
- ↑ "Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment". American Journal of Medical Genetics. Part A 164A (6): 1470–81. June 2014. doi:10.1002/ajmg.a.36545. PMID 24715559.
- ↑ "Genetic heterogeneity in familial hypercholesterolemia: evidence for two different mutations affecting functions of low-density lipoprotein receptor". Proceedings of the National Academy of Sciences of the United States of America 72 (3): 1092–6. March 1975. doi:10.1073/pnas.72.3.1092. PMID 236556. Bibcode: 1975PNAS...72.1092G.
- ↑ Keats, Bronya J. B.; Berlin, Charles I. (1999-01-01). "Genomics and Hearing Impairment" (in en). Genome Research 9 (1): 7–16. doi:10.1101/gr.9.1.7. ISSN 1088-9051. PMID 9927480. https://genome.cshlp.org/content/9/1/7.
- ↑ 9.0 9.1 9.2 "Challenges and solutions for gene identification in the presence of familial locus heterogeneity". European Journal of Human Genetics 23 (9): 1207–15. September 2015. doi:10.1038/ejhg.2014.266. PMID 25491636.
- ↑ "Detecting linkage disequilibrium in the presence of locus heterogeneity". Annals of Human Genetics 70 (Pt 3): 397–409. May 2006. doi:10.1111/j.1529-8817.2005.00229.x. PMID 16674561.
- ↑ "Evaluating genetic heterogeneity in complex disorders" (in english). Human Heredity 53 (4): 216–26. 2002. doi:10.1159/000066195. PMID 12435885.
- ↑ "Retinitis pigmentosa" (in English). Lancet 368 (9549): 1795–809. November 2006. doi:10.1016/S0140-6736(06)69740-7. PMID 17113430. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)69740-7/abstract.
- ↑ "RetNet: Summaries". https://sph.uth.edu/retnet/sum-dis.htm.
- ↑ "Retinitis pigmentosa: genes and disease mechanisms". Current Genomics 12 (4): 238–49. June 2011. doi:10.2174/138920211795860107. PMID 22131869.
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