Allelic and Locus Heterogeneity

Charles R Scriver, McGill University, Montreal, Quebec, Canada

Published online: January 2006

DOI: 10.1038/npg.els.0005481

‘Allelic heterogeneity’ implies that different alleles in the same gene can cause a similar variant phenotype. Genetic or ‘locus (nonallelic) heterogeneity’ implies that mutation in different genes may explain one variant phenotype. When simultaneous expression of mutations in different genes is necessary the phenotype is said to reflect digenic or oligogenic inheritance

Keywords: allele; databases; evolution; nomenclature; polymorphism

 References
    book Antonarakis SE, Krawczak M and Cooper DN (2001) "The nature and mechanisms of human gene mutation". In: Scriver CR, Beaudet AL, Sly WS and Valle D (eds.) The Metabolic and Molecular Bases of Inherited Disease, 8th edn, pp. 343–378. New York, NY: McGraw-Hill (Medical Publishing Division).
    Botstein D, White RL, Skolnick M and Davis RW (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms. American Journal of Human Genetics 32: 314–331.
    Cotton RGH and Scriver CR (1998) Proof of ‘disease-causing’ mutation. Human Mutation 12: 1–3.
    Gottlieb B, Beitel LK and Trifiro MA (2001) Somatic mosaicism and variable expressivity. Trends in Genetics 17: 79–82.
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    Scriver CR (2001) Garrod's foresight: our hindsight. Journal of Inherited Metabolic Disease 24: 93–116.
    book Scriver CR and Kaufman S (2001) "Hyperphenylalanemia: phenylalanine hydroxylase deficiency". In: Scriver CR, Beaudet AL, Sly WS and Valle D (eds.) The Metabolic and Molecular Bases of Inherited Disease, 8th edn, pp. 1667–1724. New York, NY: McGraw-Hill (Medical Publishing Division).
    Scriver CR and Nowacki PM (1999) Genomics, mutations and the Internet: the naming and use of parts. Journal of Inherited Metabolic Disease 22: 519–530.
    Scriver CR and Waters PJ (1999) Monogenic traits are not simple: lessons from phenylketonuria. Trends in Genetics 15: 267–272.
    Weiss KM (1996) Is there a paradigm shift in genetics? Lessons from the study of human diseases. Molecular Phylogenetics and Evolution 5: 259–265.
 Further Reading
    book Bearn AG (1993) Archibald Garrod and the Individuality of Man. Oxford, UK: Oxford University Press/Clarendon Press.
    book Hartl DL and Jones EW (2001) Genetics: Analysis of Genes and Genomes, 5th edn. London, UK: Jones and Bartlett Publishers International.
    book Kimura M (1983) The Neutral Theory of Molecular Evolution. Cambridge, UK: Cambridge University Press.
    book King RC and Stansfield WD (1997) A Dictionary of Genetics, 5th edn. Oxford, UK: Oxford University Press.
    book Strachan T and Read AP (2000) Human Molecular Genetics 2nd edn. Chichester, UK: Bios/Wiley-Liss.
 Web Links
    ePath OMIM (Online Mendelian Inheritance in Man) http://www.ncbi.nlm.nih.gov/Omim/
    ePath Phenylalanine hydroxylase locus knowledgebase http://www.pahdb.mcgill.ca/
    ePath Tetrahydrobiopterin http://www.bh4.org
    ePath AR(androgen receptor(dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease)); LocusID: 367. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=367
    ePath FGFR3(fibroblast growth factor receptor 3(achondroplasia, thanatophoric dwarfism)); LocusID: 2261. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2261
    ePath HGD(homogentisate 1,2-dioxygenase(homogentisate oxidase)); LocusID: 3081 LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3081
    ePath PAH(phenylalanine hydroxylase); LocusID: 5053. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5053
    ePath AR(androgen receptor(dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease)); MIM number: 313700 OMIM: http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?313700
    ePath FGFR3(fibroblast growth factor receptor 3(achondroplasia, thanatophoric dwarfism)); MIM number: 134934. OMIM: http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?134934
    ePath HGD(homogentisate 1,2-dioxygenase(homogentisate oxidase)); MIM number: 203500. OMIM: http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?203500
    ePath PAH(phenylalanine hydroxylase); MIM number: 261600. OMIM: http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?261600

Related Sub-Topics:

Specific Genetic Disorders | Mutational Mechanisms of Genetic Disease | Inter-Individual Variation and Polymorphism
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Article Title: Allelic and Locus Heterogeneity
 
How to Cite close
Scriver, Charles R(Jan 2006) Allelic and Locus Heterogeneity. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005481]