Human Genetics

, 124:357 | Cite as

Identifying modifier genes of monogenic disease: strategies and difficulties

  • Emmanuelle Génin
  • Josué Feingold
  • Françoise Clerget-Darpoux
Review article


Substantial clinical variability is observed in many Mendelian diseases, so that patients with the same mutation may develop a very severe form of disease, a mild form or show no symptoms at all. Among the factors that may explain these differences in disease expression are modifier genes. In this paper, we review the different strategies that can be used to identify modifier genes and explain their advantages and limitations. We focus mainly on the statistical aspects but illustrate our points with a variety of examples from the literature.


Cystic Fibrosis Genetic Modifier Modifier Gene Clinical Phenotype Spinal Muscular Atrophy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank three anonymous reviewers for their very constructive comments on this paper.s


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Emmanuelle Génin
    • 1
    • 2
    • 3
  • Josué Feingold
    • 1
    • 2
  • Françoise Clerget-Darpoux
    • 1
    • 2
    • 4
  1. 1.Inserm UMR-S535VillejuifFrance
  2. 2.Université Paris SudVillejuifFrance
  3. 3.Inserm UMR-S794, Fondation Jean Dausset-CEPHParisFrance
  4. 4.Inserm U535Villejuif CedexFrance

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