Genotype‐Phenotype Relationships


Since the beginning of the cloning of human disease‐causing genes and the identification of gene mutations, in most cases of Mendelian disorders a clear correlation between a given genotype and a particular phenotype has not been established. Understanding the complex relationships between genotypes and phenotypes is one of the greatest challenges of genetic medicine, because the elucidation of these correlations is the key to using genetic diagnosis and DNA‐based tests for the diagnosis, prognosis and surveillance of individuals affected by genetic conditions.

Keywords: genotype; phenotype; modifier genes; variable expression; locus heterogeneity; allelic heterogeneity

Further Reading

Dryja TP (1997) Gene‐based approach to human gene–phenotype correlations. Proceedings of the National Academy of Sciences of the United States of America 94: 12117–12121.

Estivill X (1996) Complexity in a monogenic disease. Nature Genetics 12: 348–350.

Feingold J (2000) Les gènes modificateurs dans les maladies héréditaires. Médecine/Sciences 16: 1–5.

Gottlieb B, Beitel LK and Trifiro MA (2001) Somatic mosaicism and variable expressivity. Trends in Genetics: TIG 17: 79–82.

Holtzman NA and Marteau TM (2000) Will genetics revolutionize medicine? New England Journal of Medicine 343: 141–144.

Nadeau JH (2001) Modifier genes in mice and human. Nature Reviews Genetics 2: 165–173.

Qian F and Germino GG (1997) “Mistakes happen”: somatic mutation and disease. American Journal of Human Genetics 61: 1000–1005.

Romeo G and McKusick VA (1994) Phenotypic diversity, allelic series and modifier genes. Nature Genetics 7: 451–453.

Suthers GK and Davies KE (1992) Phenotypic heterogeneity and the single gene. American Journal of Human Genetics 50: 887–891.

Web Links

GENATLAS. Genatlas is an interactive database collecting gene loci and their map position (more than 13000 loci at present), disease phenotypes (2900), and related literature (more than 46000) citations. http://www.dsi.univ‐

FGFR3 (fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism)); LocusID: 2261 LocusLink:

HBB (hemoglobin, beta); LocusID: 3043. LocusLink:

PAH (phenylalanine hydroxylase); LocusID: 5053. LocusLink:

RET (ret proto‐oncogene (multiple endocrine neoplasia and medullary thyroid carcinoma 1, Hirschsprung disease)); LocusID: 5979. LocusLink:

SMN1 (survival of motor neuron 1, telomeric); LocusID: 6606. LocusLink:

FGFR3 (fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism)); MIM number: 134934. OMIM:‐post/Omim/dispmim?134934

HBB (hemoglobin, beta); MIM number: 141900. OMIM:‐post/Omim/dispmim?141900

PAH (phenylalanine hydroxylase); MIM number: 261600. OMIM:‐post/Omim/dispmim?261600

RET (ret proto‐oncogene (multiple endocrine neoplasia and medullary thyroid carcinoma 1, Hirschsprung disease)); MIM number: 164761. OMIM:‐post/Omim/dispmim?164761

SMN1 (survival of motor neuron 1, telomeric); MIM number: 600354. OMIM:‐post/Omim/dispmim?600354

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How to Cite close
Lyonnet, Stanislas, Feingold, Josué, and Frézal, Jean(Sep 2006) Genotype‐Phenotype Relationships. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005476]